[{"id":"idea-mfbg-pet-replaces-mibg","kind":"idea","name":"18F-MFBG PET replacing 123I-MIBG scintigraphy","aka":[],"tldr":"A same-day PET tracer could replace the two-day, low-resolution MIBG scan children now undergo repeatedly.","summary":"Children with neuroblastoma repeatedly undergo 123I-MIBG scintigraphy, a two-day, low-resolution scan, and this idea proposes replacing it with same-day 18F-MFBG PET. 18F-meta-fluorobenzylguanidine uses the same norepinephrine-transporter biology as MIBG but gains PET resolution and 18F logistics, needs no sedation across two days, and early data show higher lesion detection. The hypothesis is that MFBG PET/CT detects more lesions than MIBG SPECT with equal specificity, and that Curie-type scoring on MFBG predicts outcome at least as well. Prospective paired comparisons are under way at MSK and in COG imaging studies and an NDA is in progress; at an early clinical stage, it sits within the paediatric oncology roadmap alongside the MIBG theranostics and PET records.","asOf":"2026-09-07","links":[{"label":"Pandit-Taskar et al., Biodistribution and dosimetry of 18F-meta-fluorobenzylguanidine: a first-in-human PET study (Journal of Nuclear Medicine 2017)","url":"https://doi.org/10.2967/jnumed.117.193169"}],"tags":[],"related":[],"cancers":["neuroblastoma"],"sections":[],"technologies":["mibg-theranostics","pet"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-pandit-taskar-j-nucl-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"18F-MFBG PET/CT detects more lesions than 123I-MIBG SPECT with equal specificity, and Curie-type scoring on MFBG predicts outcome at least as well.","rationale":"MFBG uses the same norepinephrine-transporter biology as MIBG but with PET resolution and 18F logistics.","test":"Paired prospective comparison in newly diagnosed and relapsed patients; response prediction analysis.","maturity":"early-clinical"},{"id":"idea-reg-reliance-90-day-lmic","kind":"idea","name":"90-day reliance approval for cancer drugs cleared by two stringent regulators","aka":[],"tldr":"If the FDA and EMA have both approved a cancer drug, a smaller country should be able to approve it in three months using their reports rather than starting over.","summary":"WHO's Good Reliance Practices and the WHO-Listed Authority framework already permit national regulators to rely on the assessments of stringent agencies. The proposal is a statutory 90-day abridged pathway in low- and middle-income countries for oncology medicines approved by at least two WHO-listed authorities, with the national review limited to labelling, local supply and pharmacovigilance arrangements. Swissmedic's MAGHP and the EU-M4all procedure are partial precedents.","asOf":"2026-09-08","links":[{"label":"WHO Good Reliance Practices (page moved; nearest live section)","url":"https://www.who.int/publications/i/item/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-regulatory-fragmentation","b-global-access"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Countries adopting the 90-day reliance pathway cut the median registration lag for new oncology medicines from more than two years to under one year, with no excess of safety signals relative to the originating regions.","rationale":"The scientific review has been done; the delay is administrative. Reliance is already how most vaccines reach LMICs through WHO prequalification, and the East African Community joint assessment has shown that pooled reliance shortens registration by years.","test":"Work with five countries (for example Kenya, Ghana, Nigeria, Peru and the Philippines) to adopt the pathway for oncology and measure registration lag against the WHO essential medicines list oncology section before and after.","maturity":"early-clinical","actor":"regulator","cost":"small","horizonYears":3},{"id":"idea-tr1-dose-evidence-statement-in-label","kind":"idea","name":"A 'dose evidence' panel in every label: how many doses were tested, and how","aka":[],"tldr":"A drug's label should say whether its dose was chosen by comparing several doses or simply by finding the most patients could tolerate. Doctors could then know how much room there is to reduce the dose safely.","summary":"Labels and public assessment reports include a standard panel: doses tested in humans, whether randomised dose comparison was done, the exposure-response basis, the fraction of pivotal-trial patients who required dose reduction, and any post-approval dose studies. The panel is machine-readable and aggregated publicly.","asOf":"2026-09-08","links":[{"label":"FDA Oncology Center of Excellence: Project Optimus","url":"https://www.fda.gov/about-fda/oncology-center-excellence/project-optimus"}],"tags":[],"related":["fda-approvals"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-dose-optimisation","b-knowledge-diffusion"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Making dose evidence visible will increase sponsor investment in dose optimisation before approval and will increase clinician willingness to use evidence-based dose reductions where the panel shows a flat exposure-response.","rationale":"Clinicians currently cannot tell whether a label dose is optimised or merely tolerated; transparency in other regulated domains (nutrition, energy labelling) changed both producer and consumer behaviour.","test":"Introduce the panel; survey oncologists' dose-reduction decisions for agents with and without evidence of dose optimisation, and track dose-optimisation content in submissions over five years.","maturity":"speculative","actor":"regulator","cost":"small","horizonYears":1},{"id":"idea-reg-repurposing-prize","kind":"idea","name":"A $50 million prize for the first off-patent drug proven to extend cancer survival","aka":[],"tldr":"Offer a large cash prize to whoever proves, in a rigorous trial, that a cheap existing drug helps people with cancer live longer. Prizes pull effort towards neglected problems.","summary":"Inducement prizes (the Longitude Prize, XPRIZE, the Antibiotic Longitude Prize) attract effort where markets do not. For repurposing, the payoff to society is large but no single actor can capture it. The proposal is a prize, funded by philanthropy and payers, awarded to the sponsor of the first adequately powered randomised trial showing a pre-specified overall survival improvement with an off-patent drug in a defined cancer setting, with smaller prizes for definitive negative results that close a widely used off-label practice.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (No incentive to repurpose cheap drugs): Pantziarka et al., The Repurposing Drugs in Oncology (ReDO) Project (ecancer 2014)","url":"https://doi.org/10.3332/ecancer.2014.442"}],"tags":[],"related":["clinicaltrials-gov"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-generic-repurposing","b-incentive-misalignment"],"keyPapers":["paper-pantziarka-ecancermedicalscience"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"The prize announcement is followed within three years by at least five new registered phase 3 repurposing trials that would not otherwise have been funded, and a winner within eight years.","rationale":"A prize rewards results rather than proposals, does not require the funder to pick winners, and can be sized to exceed the cost of a pragmatic phase 3 trial of a cheap drug, which is often under $20 million.","test":"Announce the prize with published criteria and an independent adjudication panel; track registration of eligible trials on ClinicalTrials.gov against the prior three-year baseline.","maturity":"speculative","actor":"philanthropy","cost":"large","horizonYears":6},{"id":"idea-prev-mced-positive-resolution-pathway","kind":"idea","name":"A 28-day national pathway for people with a positive multi-cancer blood test","aka":[],"tldr":"A positive blood test with no known tumour is frightening and hard to manage. A standard imaging cascade with a time limit, and a registry of what was found, would make these tests usable.","summary":"PATHFINDER showed diagnostic resolution sometimes took months and repeated procedures. Propose a protocolised pathway: tissue-of-origin-directed imaging first, PET-CT second, FAPI PET or whole-body MRI third, explicit stopping rules for unresolved positives (repeat test at six months), and a mandatory registry of investigations, complications, and outcomes per positive.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The hardest cancers are found late): Crosby et al., Early detection of cancer (Science 2022)","url":"https://doi.org/10.1126/science.aay9040"}],"tags":[],"related":["idea-mced-plus-fapi"],"cancers":[],"sections":["early-detection"],"technologies":["mced","fapi-pet","pet-ct","whole-body-mri"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["ppv"],"trials":[],"people":[],"bottlenecks":["b-early-detection","b-overdiagnosis"],"keyPapers":["paper-crosby-science"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A protocolised pathway achieves diagnostic resolution within 28 days in at least 80% of positives with two or fewer imaging procedures on average, and halves invasive procedures per false positive relative to unstructured care.","rationale":"NHS Rapid Diagnostic Centres already do this for non-specific symptoms; the MCED positive is a new referral reason for the same machinery.","test":"Compare structured versus usual-care resolution in the NHS-Galleri implementation phase.","maturity":"early-clinical","actor":"clinic","cost":"medium","horizonYears":3},{"id":"idea-fund-cure-prize","kind":"idea","name":"A billion-dollar prize for the first durable cure of a lethal metastatic cancer","aka":[],"tldr":"Governments and foundations would pool a prize of about a billion dollars into an escrowed fund, paid only when a treatment is shown in a well-controlled registration cohort to keep most patients with a currently incurable metastatic cancer, such as pancreatic adenocarcinoma or glioblastoma, disease-free for five years. The winner keeps its patent but accepts a price ceiling.","summary":"A pull incentive that pays for the outcome the system currently under-rewards. The prize is defined in advance per disease (for example metastatic pancreatic adenocarcinoma, glioblastoma, metastatic TNBC) with an objective bar such as at least 50% five-year disease-free survival in a randomised or well-controlled registration cohort where the historical figure is under 5%. The winner keeps its patent but accepts a price ceiling and global access licensing as a condition. Multiple sponsors could pool into a single escrowed fund; a partial prize could be paid for intermediate milestones (for example 25% durable remission).","asOf":"2026-09-08","links":[{"label":"XPRIZE","url":"https://www.xprize.org/"},{"label":"Longitude Prize","url":"https://longitudeprize.org/"}],"tags":[],"related":["idea-fund-first-in-class-prize","idea-fund-value-based-patent-extension"],"cancers":["pancreatic","glioblastoma","tnbc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-incentive-misalignment","b-metastasis-biology"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A credible, escrowed cure prize of one billion dollars or more per disease increases the number of registered first-in-class programmes in the named diseases by at least half within five years and attracts new entrants (academic spin-outs, non-oncology companies) that the current market does not.","rationale":"Pull mechanisms have worked where the goal is well-specified and the market signal weak: the Ansari X Prize, the Longitude Prize, Gavi's advance market commitment and DARPA challenges. Current oncology rewards are indifferent to magnitude of benefit, so capital flows to predictable incremental gains; a prize inverts the payoff curve for the hardest problems.","test":"Announce a single-disease prize with a fully escrowed fund and pre-registered success criteria, then track new programme registrations, venture funding and phase 1 starts in that disease against matched diseases without a prize over five years.","maturity":"speculative","actor":"policy","cost":"large","horizonYears":10},{"id":"idea-reg-vitamin-d-digestive-cancer-biomarker-trial","kind":"idea","name":"A biomarker-directed trial of vitamin D after surgery for digestive tract cancers","aka":[],"tldr":"A Japanese trial found vitamin D supplements did not help everyone after digestive cancer surgery, but appeared to help a subgroup identified by a tumour marker. That subgroup deserves its own trial.","summary":"The AMATERASU trial of vitamin D3 after surgery for digestive tract cancers was negative overall, but pre-specified and post-hoc analyses reported large relapse and death reductions in subgroups (p53-immunoreactive tumours, low-to-mid baseline vitamin D). Similar biomarker-restricted signals appeared in SUNSHINE (colorectal, high-dose vitamin D with chemotherapy). Vitamin D is nearly free. The proposal is a confirmatory randomised trial restricted to the biomarker-defined subgroup, with relapse-free survival as the primary endpoint, funded publicly.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (No incentive to repurpose cheap drugs): Pantziarka et al., The Repurposing Drugs in Oncology (ReDO) Project (ecancer 2014)","url":"https://doi.org/10.3332/ecancer.2014.442"}],"tags":[],"related":[],"cancers":["colorectal","gastric","esophageal"],"sections":[],"technologies":[],"targets":["tp53"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-generic-repurposing","b-biomarker-validation"],"keyPapers":["paper-pantziarka-ecancermedicalscience"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Vitamin D3 2,000 IU daily improves 5-year relapse-free survival by at least 10 absolute percentage points in patients with p53-immunoreactive digestive tract cancers after curative surgery.","rationale":"Subgroup findings from a negative trial are usually false, but this one was pre-specified in part, is mechanistically plausible and is being echoed in a second trial; the cost of a definitive test is trivial relative to the potential benefit in common cancers.","test":"Randomised placebo-controlled trial of about 800 biomarker-positive patients across Japan and Europe with RFS primary endpoint and serum vitamin D monitoring.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":6},{"id":"idea-bio2-premetastatic-niche-assay","kind":"idea","name":"A blood test for the pre-metastatic niche","aka":[],"tldr":"Before cancer spreads, distant organs are changed to become welcoming. A test for those changes would show which organ is at risk while a person still looks cancer-free.","summary":"Pre-metastatic niche formation involves tumour-derived exosome integrins, S100A8 and S100A9 induction, myeloid mobilisation and fibronectin deposition in the target organ. Candidate readouts exist (plasma S100A8/A9, exosomal integrin profiles, circulating LOX activity, neutrophil trajectories) but nobody has assembled them into a validated organ-specific risk assay.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Metastasis is understood least and studied last): Dillekås et al., Are 90% of deaths from cancer caused by metastases? (Cancer Medicine 2019)","url":"https://doi.org/10.1002/cam4.2474"}],"tags":[],"related":[],"cancers":["colorectal","breast-hr-positive","pancreatic"],"sections":[],"technologies":["proteomics","liquid-biopsy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-metastasis-biology","b-dormancy-mrd","b-biomarker-validation"],"keyPapers":["paper-dillekas-cancer-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A multi-analyte niche score measured after curative surgery predicts organ-specific relapse (lung versus liver versus bone) with a c-statistic above 0.75, independently of and additively to ctDNA.","rationale":"Exosomal integrin patterns predicted lung and liver organotropism respectively in mouse and human samples. Organ-specific prediction would let prevention be targeted to one organ, which a single ctDNA yes-or-no answer cannot do.","test":"Nested case-control study in two existing adjuvant trial biobanks with known relapse sites; lock the score, then validate it prospectively in a third cohort.","maturity":"speculative","actor":"research","cost":"medium","horizonYears":7},{"id":"idea-prev-brca1-denosumab-prevention","kind":"idea","name":"A bone drug to prevent breast cancer in BRCA1 carriers","aka":[],"tldr":"BRCA1 breast cancers seem to grow from cells driven by the RANK signal. Denosumab blocks it and is already used for bone. A trial is testing whether it prevents these cancers.","summary":"BRCA1 breast cancers appear to grow from progenitor cells driven by RANKL signalling, and denosumab, already used for bone, blocks it, so this idea supports completion of the ABCSG BRCA-P trial, which randomises BRCA1 carriers to denosumab or placebo with breast cancer incidence as the endpoint, and prepares implementation pathways for a positive result. Preclinical and window-of-opportunity data show reduced proliferation in carrier breast tissue. The test is the BRCA-P readout followed, if positive, by an implementation study with uptake and adherence endpoints. Being tested at scale, it addresses the bottleneck Inherited risk is mostly unidentified and links to chemoprevention, BRCA and TNBC.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Inherited risk is mostly unidentified): Childers et al., National estimates of genetic testing in women with breast or ovarian cancer (JCO 2017)","url":"https://doi.org/10.1200/JCO.2017.73.6314"}],"tags":[],"related":[],"cancers":["tnbc"],"sections":["prevention"],"technologies":["chemoprevention"],"targets":["brca"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-hereditary-risk"],"keyPapers":["paper-childers-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Denosumab reduces breast cancer incidence in BRCA1 carriers by at least 40%.","rationale":"Preclinical and window-of-opportunity data show reduced proliferation in carrier breast tissue.","test":"BRCA-P readout; if positive, an implementation study with uptake and adherence endpoints.","maturity":"being-tested-at-scale","actor":"research","cost":"large","horizonYears":5},{"id":"idea-bio2-marrow-niche-on-chip","kind":"idea","name":"A bone marrow niche on a chip to study human dormancy","aka":[],"tldr":"Dormant cancer cells hide in bone marrow. A lab-built model of that hiding place would let us watch them sleep and wake, and test drugs on them.","summary":"Microfluidic and organ-on-chip systems can now sustain human haematopoietic niches with mesenchymal stroma, osteoblasts and vasculature under flow. Adding patient-derived tumour cells creates a human dormancy model with live-cell imaging, in which awakening triggers such as inflammation, chemotherapy or niche disruption can be dialled in and quantified.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Dormant cells and minimal residual disease): Tie et al., ctDNA analysis guiding adjuvant therapy in stage II colon cancer (NEJM 2022)","url":"https://doi.org/10.1056/NEJMoa2200075"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["organoids","functional-drug-testing","single-cell-spatial"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["mrd"],"trials":[],"people":[],"bottlenecks":["b-dormancy-mrd","b-preclinical-models"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Human marrow-niche chips reproduce the entry into and exit from dormancy and rank pro-dormancy or dormancy-killing compounds concordantly with in vivo models, making them a valid first-line assay.","rationale":"Dormancy depends on niche cell contacts and flow that plastic dishes cannot supply, which is why the field is stuck on mouse studies. Liver and gut chips have already been accepted for some regulatory-grade toxicology, so the engineering path is known.","test":"Benchmark a chip against paired in vivo data with a blinded compound set of known dormancy modulators and inactive controls; publish concordance, cost and throughput.","maturity":"preclinical-evidence","actor":"engineering","cost":"medium","horizonYears":6},{"id":"idea-prev-breath-voc-symptomatic-ruleout","kind":"idea","name":"A breath test to rule out cancer in people with vague symptoms","aka":[],"tldr":"Volatile compounds in breath differ in cancer. A breath test validated in truly symptomatic patients, not lab volunteers, could tell GPs who needs urgent scans and who can safely wait.","summary":"Breath VOC studies are mostly case-control and fail on replication. Propose validation exclusively in prospective symptomatic primary-care cohorts, targeting a rule-out use (negative predictive value above 99%) rather than diagnosis, with locked classifiers and external validation before any clinical use.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The hardest cancers are found late): Crosby et al., Early detection of cancer (Science 2022)","url":"https://doi.org/10.1126/science.aay9040"}],"tags":[],"related":[],"cancers":[],"sections":["early-detection","diagnostics"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["ppv"],"trials":[],"people":[],"bottlenecks":["b-early-detection","b-biomarker-validation"],"keyPapers":["paper-crosby-science"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A breath VOC panel achieves at least 99% NPV for any cancer within 12 months in symptomatic patients aged 50 and over, allowing safe deferral of imaging in at least 40% of referrals.","rationale":"The rule-out use case tolerates imperfect specificity and matches the actual clinical bottleneck, which is imaging capacity.","test":"5,000-patient prospective cohort through Rapid Diagnostic Centres with a pre-registered analysis plan.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":4},{"id":"idea-gbc-burden-to-funding-audit-and-dedicated-call","kind":"idea","name":"A burden-to-funding audit for gallbladder cancer and a dedicated research call","aka":[],"tldr":"Gallbladder cancer has been called scantily understood in 2004 and understudied in 2025 by its own researchers. Counting the money spent on it against the deaths it causes, country by country, would make the gap visible and give funders a target.","summary":"The disease is common in Chile, Bolivia, northern India and parts of East Asia and rare in the countries that fund most cancer research; it is treated mostly by surgeons and pooled with cholangiocarcinoma in trials, so it has neither an advocacy base nor a trial portfolio of its own. Successive reviews (Wistuba and Gazdar 2004; Roa 2022; Zhu 2025) describe it as understudied and list the same unmet needs: screening biomarkers, standardised pathology, separate trials. The EULAT Eradicate GBC consortium (EU Horizon 2020) shows what a dedicated call can build. An audit of research spend against disability-adjusted life years, published and repeated, is the cheapest lever, followed by a targeted call from a funder with reach into both high-incidence and high-capacity countries.","asOf":"2026-09-24","links":[{"label":"Wistuba and Gazdar: gallbladder cancer, lessons from a rare tumour (Nat Rev Cancer 2004)","url":"https://europepmc.org/article/MED/15343276"},{"label":"Scherer et al.: EULAT Eradicate GBC, the European-Latin American research consortium (Int J Epidemiol 2025)","url":"https://europepmc.org/article/MED/40735836"}],"tags":["gallbladder-evidence"],"related":["globocan"],"cancers":["gallbladder"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["cruk","nci","iarc"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-funding-allocation","b-rare-cancers","b-incentive-misalignment"],"keyPapers":["paper-wistuba-gazdar-gallbladder-cancer-lessons-nat-rev-cancer-2004","paper-roa-gallbladder-cancer-primer-nat-rev-dis-primers-2022","paper-zhu-population-specific-immunogenomics-gallbladder-cancer-mod-pathol-2025"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Publishing an annual burden-to-funding ratio for gallbladder cancer alongside other gastrointestinal cancers, and pairing it with a dedicated multi-country call, will at least double registered interventional trials naming gallbladder cancer as a primary population within five years.","rationale":"Funding follows visibility; the disease's incidental diagnosis and trial pooling have kept it invisible in exactly the systems that allocate research money.","test":"Baseline audit using funder databases (NIH RePORTER, UKRI Gateway, Horizon Europe, CRUK) against GLOBOCAN burden; count of interventional trials with gallbladder cancer as primary population on ClinicalTrials.gov before and after a targeted call.","maturity":"speculative","actor":"philanthropy","cost":"small","horizonYears":3},{"id":"idea-prev-emergency-department-cancer-test","kind":"idea","name":"A cancer blood test for older people arriving at A&E with unexplained symptoms","aka":[],"tldr":"One in five cancers in the UK is first found in an emergency, usually late. Adding a cancer test to the blood already taken in A&E for over-60s with vague symptoms could catch some earlier.","summary":"Emergency presentation carries much worse survival, and these patients often attended A&E months earlier with non-specific complaints. Propose adding an MCED or targeted marker panel to blood drawn in emergency departments for patients aged 60 and over with weight loss, anaemia, or non-specific pain, with a defined follow-up route.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The hardest cancers are found late): Crosby et al., Early detection of cancer (Science 2022)","url":"https://doi.org/10.1126/science.aay9040"}],"tags":[],"related":[],"cancers":[],"sections":["early-detection"],"technologies":["mced"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-early-detection","b-care-fragmentation"],"keyPapers":["paper-crosby-science"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Emergency department add-on testing detects cancer in at least 3% of tested patients, with at least half at stage I-III, and reduces subsequent emergency-route diagnoses in the tested population.","rationale":"Emergency-department patients have high pre-test probability and are already having blood drawn; the missed opportunity is documented in linked-data studies.","test":"Pilot in three emergency departments, 5,000 tests, registry-linked outcomes.","maturity":"speculative","actor":"clinic","cost":"medium","horizonYears":3},{"id":"idea-data-donor-card","kind":"idea","name":"A cancer data donor card: patient-controlled donation of records for research","aka":[],"tldr":"Like an organ donor card, anyone with cancer could sign once to let their medical records and leftover samples be used for research, and change their mind at any time.","summary":"Most cancer patients say they would share their data for research, yet consent is sought piecemeal per study. The proposal is a national, patient-initiated registration (via the patient portal or a paper card) that grants broad, revocable consent for secondary use of records, images and residual tissue, with a public dashboard of what the data have been used for. Count Me In and the UK Biobank show that broad consent at scale is feasible; the Metastatic Breast Cancer Project enrolled thousands of patients directly.","asOf":"2026-09-08","links":[{"label":"Count Me In","url":"https://joincountmein.org/"}],"tags":[],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":["patient-data-vault","cancer-commons"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-data-silos","b-patient-voice"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Offering broad revocable data donation at diagnosis will be accepted by more than 70 percent of patients and will double the sample size available to registry-linked studies within five years, with withdrawal below 3 percent.","rationale":"Surveys consistently show 70 to 90 percent willingness to share; the barrier is that no one asks in a standard, portable way. Organ donation registers show that a one-time civic act can be scaled.","test":"Pilot in ten cancer centres: offer the donor card at first oncology visit, measure uptake, withdrawal and demographic skew over 24 months; compare research-ready cohort size with matched centres that do not offer it.","maturity":"speculative","actor":"patients","cost":"medium","horizonYears":3},{"id":"idea-moon-misinformation-rapid-response","kind":"idea","name":"A cancer misinformation rapid-response unit that rebuts within 48 hours","aka":[],"tldr":"A small team monitors social media and news for spreading cancer falsehoods and publishes clear, sourced rebuttals within two days, before the claim becomes established.","summary":"Public health agencies built infodemic units during COVID-19 but cancer has no equivalent. The proposal is a standing unit (hosted by a national cancer institute or charity) using social listening to detect fast-growing false claims about cancer causes, cures and treatments, producing plain rebuttals with primary sources within 48 hours, and distributing them through clinician networks, platforms and patient organisations. Impact is measured through claim spread trajectories and clinic reports.","asOf":"2026-09-08","links":[{"label":"WHO infodemic management","url":"https://www.who.int/health-topics/infodemic"}],"tags":[],"related":["fenbendazole-ivermectin-repurposing-claims"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-misinformation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Rapid rebuttal reduces the reach of targeted false claims by at least a third compared with matched untreated claims, and reduces patient questions about those claims in clinic.","rationale":"Misinformation compounds with time; early, sourced counter-messaging from trusted voices is the best-evidenced countermeasure short of platform action.","test":"Run the unit for a year with claims randomised to rapid rebuttal or observation; compare spread metrics and clinic survey data.","maturity":"early-clinical","actor":"philanthropy","cost":"small","horizonYears":1},{"id":"idea-prev-genetic-counselling-chatbot","kind":"idea","name":"A chatbot for pre-test genetic counselling so counsellors see only who needs them","aka":[],"tldr":"There are far too few genetic counsellors. A validated chatbot can do the standard pre-test education, leaving people with complex needs for humans.","summary":"There are far too few genetic counsellors, so this idea uses validated language-model counselling assistants with safety guardrails for standard pre-test education in population and cascade testing, leaving people with complex needs for human counsellors. The BRIDGE trial showed chatbot pre-test education was non-inferior to counsellor delivery for testing uptake, and workforce is the rate-limiter for expanding germline testing. The aim is non-inferior knowledge and decisional conflict scores with several times the throughput per counsellor. The test is a non-inferiority RCT in 2,000 patients. At early-clinical maturity it addresses the bottlenecks Inherited risk is mostly unidentified and Not enough oncologists, nurses, pathologists, physicists.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Inherited risk is mostly unidentified): Childers et al., National estimates of genetic testing in women with breast or ovarian cancer (JCO 2017)","url":"https://doi.org/10.1200/JCO.2017.73.6314"}],"tags":[],"related":[],"cancers":[],"sections":["prevention","ai-computation"],"technologies":["germline-testing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-hereditary-risk","b-workforce"],"keyPapers":["paper-childers-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Chatbot-delivered pre-test education achieves non-inferior knowledge and decisional conflict scores with at least five times the throughput per counsellor.","rationale":"Workforce is the rate-limiter for expanding germline testing.","test":"Run a non-inferiority RCT in 2,000 patients.","maturity":"early-clinical","actor":"engineering","cost":"small","horizonYears":2},{"id":"idea-bio2-low-dose-olanzapine-appetite","kind":"idea","name":"A cheap old tablet to restore appetite","aka":[],"tldr":"A low dose of an old, inexpensive tablet improved appetite and weight in a randomised trial of people with advanced cancer. It could be used almost everywhere tomorrow.","summary":"Low-dose olanzapine, at 2.5 mg daily, improved appetite, weight gain and quality of life versus placebo in a randomised trial in patients with advanced gastrointestinal and lung cancer receiving chemotherapy, conducted at Tata Memorial. The drug is generic, oral, off-patent and already used for chemotherapy-induced nausea, so implementation requires guideline change rather than development.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Cachexia, toxicity and the limits of the patient): Fearon et al., Definition and classification of cancer cachexia (Lancet Oncology 2011)","url":"https://doi.org/10.1016/S1470-2045(10)70218-7"}],"tags":[],"related":["nccn","esmo-guidelines"],"cancers":["gastric","nsclc","colorectal"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["tata-memorial"],"pathways":[],"terms":[],"trials":[],"people":["gupta-sudeep"],"bottlenecks":["b-cachexia-supportive","b-generic-repurposing","b-global-access"],"keyPapers":["paper-fearon-lancet-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Low-dose olanzapine as standard supportive care for cancer-related anorexia improves weight, appetite and chemotherapy completion rates in routine practice, replicating the trial result at population scale.","rationale":"The mechanism, appetite stimulation with a favourable metabolic profile at low dose, is well established in psychiatry, and the drug already appears in antiemetic guidelines so safety monitoring is familiar. Cost is negligible in almost every health system.","test":"Run a pragmatic multi-country replication trial, particularly in low- and middle-income settings, with appetite, weight, quality of life and metabolic adverse events as endpoints; then guideline adoption.","maturity":"early-clinical","actor":"clinic","cost":"small","horizonYears":3},{"id":"idea-bio1-ctdna-clone-report","kind":"idea","name":"A clone report from blood at every treatment cycle","aka":[],"tldr":"Blood tests can already detect tumour DNA. Reporting which sub-populations of the tumour are growing or shrinking, cycle by cycle, would turn the test into an evolution monitor.","summary":"Phylogenetic ctDNA analysis, as developed in TRACERx, assigns plasma variants to tumour subclones and tracks their relative abundance. The proposal is a standardised clinical report in which each ctDNA draw lists clone fractions, emergent clones, and clone-specific drug sensitivities, rather than a flat list of variants and allele frequencies.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Tumour heterogeneity and clonal evolution): Gerlinger et al., Intratumor heterogeneity and branched evolution (NEJM 2012)","url":"https://doi.org/10.1056/NEJMoa1113205"}],"tags":[],"related":["idea-ctdna-switch-generalised"],"cancers":["nsclc"],"sections":[],"technologies":["liquid-biopsy","mrd-testing"],"targets":[],"drugs":["osimertinib"],"companies":[],"institutions":[],"pathways":[],"terms":["ctdna","vaf"],"trials":[],"people":[],"bottlenecks":["b-tumor-heterogeneity","b-resistance"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Clone-level ctDNA reporting detects the expansion of a resistant subclone a median of three or more months before radiographic progression and changes management in at least a fifth of patients on targeted therapy.","rationale":"Resistance is subclone expansion. Existing panels report VAFs without the phylogenetic context that distinguishes clonal shrinkage from branch escape. The maths exists; the reporting format does not.","test":"Retrospective analysis on serial plasma from a completed TKI trial to compute lead time; then a prospective single-arm study in EGFR or ALK lung cancer where clinicians receive clone reports and act on pre-specified rules.","maturity":"early-clinical","actor":"data","cost":"medium","horizonYears":3},{"id":"idea-reg-combination-price-attribution","kind":"idea","name":"A combination pricing rule so two-drug regimens are not priced as two monopolies","aka":[],"tldr":"When two expensive cancer drugs are combined, the price is often the sum of both even though the extra benefit is smaller. A rule for splitting the total value between them is needed.","summary":"Combination regimens (checkpoint inhibitor plus targeted agent, ADC plus immunotherapy) frequently fail cost-effectiveness thresholds because each manufacturer prices for the full value, and competition law is cited as blocking joint negotiation. The UK's 2023 ABPI-NICE combination framework allows a backbone manufacturer to offer a rebate when its drug is used as part of a combination. The proposal is to generalise this: payers set a total price ceiling for the regimen based on its incremental benefit, a published attribution rule splits it between components, and competition authorities issue safe-harbour guidance for the resulting arrangements.","asOf":"2026-09-08","links":[{"label":"NICE combination treatments framework (page moved; nearest live section)","url":"https://www.nice.org.uk/about/what-we-do/our-programmes/nice-guidance/nice-technology-appraisal-guidance/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-drug-pricing","b-combination-space"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Under the framework, the proportion of combination regimens recommended by HTA bodies rises by at least a third, and total regimen prices fall relative to the sum of monotherapy prices.","rationale":"The best new regimens are increasingly combinations of drugs from different companies; without an attribution mechanism, patients lose access to the most effective treatments because of a pricing coordination failure rather than any scientific limitation.","test":"Evaluate uptake and prices of combinations assessed under the UK framework over three years; adopt the framework in two other payers with competition-authority guidance and compare recommendation rates.","maturity":"early-clinical","actor":"payer","cost":"small","horizonYears":3},{"id":"idea-data-common-biobank-consent-mta","kind":"idea","name":"A common consent and material transfer template for tumour biobanks","aka":[],"tldr":"Every biobank negotiates its own legal agreement for sharing tissue, which takes months. A shared standard template, like Creative Commons for samples, would let tissue and data move in days.","summary":"Material transfer agreements are negotiated bespoke; consent forms differ; the result is that tumour samples rarely leave the institution that collected them. A common consent text recognised by ethics committees and a standard tiered MTA (academic, commercial, with fixed benefit-sharing terms) would remove most negotiation. Precedents include the Uniform Biological Material Transfer Agreement (UBMTA) and the Global Alliance for Genomics and Health consent toolkit.","asOf":"2026-09-08","links":[{"label":"GA4GH","url":"https://www.ga4gh.org/"}],"tags":[],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-data-silos","b-ip-collaboration"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Adoption of a common template by more than 50 biobanks will cut median time to sample transfer from over six months to under one and increase the number of samples used in multi-centre studies.","rationale":"Standard licences (Creative Commons, open-source software licences) removed negotiation costs and created ecosystems; biobanking has the templates but not the adoption push.","test":"Get ten biobanks and their legal offices to adopt the template; track transfer time and volume for 18 months against the previous period.","maturity":"speculative","actor":"research","cost":"small","horizonYears":2},{"id":"idea-fund-trial-biospecimen-commons","kind":"idea","name":"A commons for leftover trial biospecimens with standard access for approved research","aka":[],"tldr":"Blood and tissue samples collected in cancer trials are the best material for validating new tests, but most sit unused under contracts that make access impossible. A commons would make them available for approved research.","summary":"Sponsors and academic trial groups deposit or catalogue residual biospecimens from completed trials (with linked clinical outcomes) in a federated commons with a single access committee, standard consent language for future trials that permits secondary research, and cost-recovery pricing. Access priority goes to biomarker validation studies and to negative-trial samples that can explain why drugs failed. The NCI's cooperative group banks and the EORTC's SPECTA show the model at small scale; the change is universal deposit obligations and one door to knock on.","asOf":"2026-09-08","links":[{"label":"UK Biobank","url":"https://www.ukbiobank.ac.uk/"}],"tags":[],"related":["idea-fund-biomarker-validation-fund","idea-fund-trial-data-trust"],"cancers":[],"sections":[],"technologies":["companion-diagnostic","liquid-biopsy","proteomics"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-ip-collaboration","b-biomarker-validation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A biospecimen commons increases the number of biomarker validation studies using randomised-trial samples by at least threefold within three years and reduces the median time from request to sample receipt to under six months.","rationale":"Prospective-retrospective validation on trial samples is the recognised gold standard for predictive biomarkers, and the main obstacle reported by investigators is access, not science. Standard consent and single access committees have worked for national biobanks such as UK Biobank.","test":"Pilot deposit from five completed trials with a standard access process; measure requests, approvals, time to receipt and studies published over two years.","maturity":"early-clinical","actor":"data","cost":"medium","horizonYears":3},{"id":"idea-tr2-shelved-asset-commons","kind":"idea","name":"A commons of shelved cancer drugs with their full data, open to new hypotheses","aka":[],"tldr":"Companies shelve drugs that were safe but failed in the disease they tried. An oncology commons cataloguing discontinued assets with their mechanism, human pharmacokinetics, safety data and reasons for discontinuation, under template access terms, would let others test them where they might work, as NCATS and AstraZeneca schemes have shown.","summary":"The NCATS New Therapeutic Uses programme, the AstraZeneca Open Innovation portfolio and the Medical Research Council industry asset-sharing scheme have shown that shelved compounds can be repurposed when made available with their data. An oncology-focused commons with a searchable catalogue of discontinued assets (mechanism, human pharmacokinetics, safety database, reasons for discontinuation) and template access terms would systematise this.","asOf":"2026-09-08","links":[{"label":"NCATS New Therapeutic Uses","url":"https://ncats.nih.gov/research/research-activities/ntu"}],"tags":[],"related":["idea-tr2-termination-reports","drugbank-chembl"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-negative-results","b-translational-valley"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"At least ten discontinued oncology assets will enter new investigator-initiated trials within three years of the commons opening, at least one reaching a positive randomised result within seven years.","rationale":"Many failures are indication failures, not molecule failures. Human safety data is the most expensive thing a shelved drug carries, and it is wasted when the drug sits on a shelf.","test":"Launch with five sponsors contributing twenty assets; track access requests, trials started and outcomes.","maturity":"early-clinical","actor":"industry","cost":"medium","horizonYears":3},{"id":"idea-data-surgical-video-commons","kind":"idea","name":"A consented commons of surgical video linked to pathology and outcomes","aka":[],"tldr":"Record cancer operations (with consent), link each video to the pathology report and the patient's recovery, and open the collection to researchers to learn what surgical technique actually works.","summary":"Robotic and laparoscopic cancer surgery is routinely video-recorded, yet the recordings are deleted. A governed commons linking de-identified surgical video to margin status, lymph node yield, complications and survival would allow surgical technique to be studied at scale and surgical AI (phase recognition, skill assessment) to be validated against outcomes. Academic skill-assessment studies have already shown that surgeon skill rated from video predicts outcomes.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Data silos): AACR Project GENIE","url":"https://www.aacr.org/professionals/research/aacr-project-genie/"}],"tags":[],"related":[],"cancers":[],"sections":["ai-computation","surgery"],"technologies":["robotic-surgery"],"targets":[],"drugs":[],"companies":["intuitive-surgical"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-data-silos","b-surgery-radiation-innovation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Video-derived measures of technique and skill will explain a meaningful share of between-surgeon variation in positive margins and complications, and feedback based on them will reduce that variation.","rationale":"Birkmeyer et al. (NEJM 2013) showed peer-rated surgical skill from video predicts complication rates; the tools to scale this with AI exist but lack data.","test":"Collect 2,000 consented robotic prostatectomy or colectomy videos across five centres with linked outcomes; test whether automated skill scores predict positive margins and 30-day complications.","maturity":"speculative","actor":"research","cost":"medium","horizonYears":4},{"id":"idea-fund-flash-evidence-programme","kind":"idea","name":"A coordinated FLASH radiotherapy evidence programme with shared dose-rate standards","aka":[],"tldr":"Ultra-fast radiotherapy may spare healthy tissue while still killing tumours, but every centre is testing it differently. A coordinated programme would agree the measurements and run the trials that settle whether it works.","summary":"FLASH radiotherapy (dose delivered in under a second at ultra-high dose rate) shows a normal-tissue sparing effect in animals; the first human trial (FAST-01, proton FLASH for bone metastases) showed feasibility. Evidence is fragmented across manufacturers and centres with different beam types (electron, proton, photon prototypes), dose-rate definitions and dosimetry. The programme would fund a consortium to standardise dosimetry and dose-rate reporting, build a shared preclinical platform to define the biological conditions of the effect, and run coordinated multi-centre phase 2 and randomised trials in indications where normal-tissue toxicity limits cure (head and neck, thoracic, paediatric). Without coordination the field risks a decade of unconvincing small studies.","asOf":"2026-09-08","links":[{"label":"FAST-01 (NCT04592887)","url":"https://clinicaltrials.gov/study/NCT04592887"}],"tags":[],"related":["idea-fund-radiotherapy-trials-infrastructure","idea-fund-proton-coverage-with-evidence"],"cancers":["head-and-neck","nsclc"],"sections":[],"technologies":["flash-rt","proton-therapy"],"targets":[],"drugs":[],"companies":["varian","iba"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-surgery-radiation-innovation","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A coordinated programme produces, within six years, a randomised trial demonstrating whether FLASH reduces a pre-specified grade 3 or higher toxicity endpoint by at least a third at equal tumour control in a curative indication, settling the clinical question one way or the other.","rationale":"Preclinical FLASH sparing has been reproduced across species and tissues, but the mechanism and required beam parameters are debated; the history of proton therapy shows that letting technology diffuse before randomised evidence produces decades of unresolved argument. Coordinated dosimetry standards were what made IMRT and SBRT trials interpretable.","test":"Fund the consortium with mandatory shared dosimetry, complete a multi-centre phase 2 in one indication within three years, and launch a randomised trial with a toxicity primary endpoint.","maturity":"early-clinical","actor":"research","cost":"large","horizonYears":6},{"id":"idea-reg-medical-isotope-reactor-reserve","kind":"idea","name":"A coordinated reserve and shared schedule for the world's medical isotope reactors","aka":[],"tldr":"A handful of ageing research reactors make most cancer isotopes. Coordinating their maintenance and funding reserve capacity would prevent the shortages that stop treatments.","summary":"Lutetium-177, iodine-131 and molybdenum-99 depend on a few research reactors (HFR Petten, BR2, MARIA, SAFARI-1, OPAL, several in Russia and the US), most over 50 years old. The OECD Nuclear Energy Agency's High-Level Group on Medical Radioisotopes coordinated molybdenum-99 after the 2009-10 crisis. The proposal is to extend that model formally to therapeutic isotopes: shared outage scheduling, an agreed reserve capacity margin funded by a per-dose levy, and public co-financing of the next generation of producers (PALLAS in the Netherlands, accelerator-based SHINE, new irradiation positions in existing reactors).","asOf":"2026-09-08","links":[{"label":"OECD NEA medical radioisotopes","url":"https://www.oecd-nea.org/jcms/pl_26262/medical-radioisotopes"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["radioligand-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-manufacturing-cell-therapy","b-global-access"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Coordinated scheduling and reserve capacity reduce clinic-reported therapeutic isotope shortage weeks by at least 80% and keep lutetium-177 spot prices stable during planned reactor outages.","rationale":"The molybdenum-99 experience showed that coordination, not new physics, ended a supply crisis; therapeutic isotopes now face the same concentration of supply with faster-growing demand.","test":"Publish a shared outage calendar and reserve-margin target for lutetium-177 producers within a year; track clinic-reported dose cancellations and prices against the prior three years.","maturity":"early-clinical","actor":"policy","cost":"large","horizonYears":5},{"id":"idea-gbc-ctdna-residual-disease-guided-adjuvant-trial","kind":"idea","name":"A ctDNA residual disease-guided adjuvant trial after gallbladder cancer resection","aka":[],"tldr":"After surgery for bile duct or gallbladder cancer, a blood test for leftover tumour DNA picks out the people whose cancer will return with hazard ratios of 16 to 26 in two recent cohorts. Nobody has yet tested giving those people more than the standard capecitabine.","summary":"Tumour-informed ctDNA in the 2 to 12 week window after biliary resection was positive in 23 percent of 167 patients and carried a relapse-free survival hazard ratio of 15.86 (Malla 2026); in a 56-patient cohort the hazard ratio was 26 (Yu 2025). Gallbladder cancer recurs early and distantly after re-resection (Varshney 2025), which is the setting where a residual disease test could pick who gets escalation. The template exists in colon and bladder cancer (DYNAMIC, IMvigor011). A biliary trial would randomise ctDNA-positive patients after resection to capecitabine or gemcitabine-cisplatin with durvalumab, and could de-escalate ctDNA-negative T1b or T2a patients to observation.","asOf":"2026-09-24","links":[{"label":"Malla et al.: real-world ctDNA after resection of stage I to III biliary tract cancer (ESMO GI Oncol 2026)","url":"https://europepmc.org/article/MED/42583118"},{"label":"Yu et al.: ctDNA and early recurrence after biliary resection (JCO Precis Oncol 2025)","url":"https://europepmc.org/article/MED/39772829"}],"tags":["gallbladder-evidence"],"related":["ctdna-tests","idea-btc-ctdna-fgfr-resistance"],"cancers":["gallbladder","biliary-tract-cancer"],"sections":[],"technologies":["liquid-biopsy","mrd-testing"],"targets":[],"drugs":["signatera","capecitabine","gemcitabine-cisplatin","durvalumab"],"companies":[],"institutions":[],"pathways":[],"terms":["ctdna","mrd","neoadjuvant-adjuvant","de-escalation"],"trials":["bilcap","acticca-1"],"people":[],"bottlenecks":["b-dormancy-mrd","b-trial-design"],"keyPapers":["paper-malla-ctdna-resected-biliary-tract-cancer-esmo-gi-onc-2026","paper-yu-ctdna-early-recurrence-biliary-tract-cancer-jco-po-2025"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"In resected gallbladder cancer with detectable ctDNA at 4 to 8 weeks, adjuvant gemcitabine-cisplatin plus durvalumab improves two-year recurrence-free survival over capecitabine by at least 15 percentage points; in ctDNA-negative early-stage disease, observation is non-inferior to capecitabine.","rationale":"Residual disease positivity is the strongest prognostic factor yet measured after biliary resection, and stronger than CA 19-9; adjuvant capecitabine's benefit is unproven in gallbladder cancer specifically.","test":"Two-cohort randomised trial (escalation in ctDNA-positive, de-escalation in ctDNA-negative) nested in a national incidental cancer pathway, with tumour-informed assay from the resection specimen; about 400 patients over four years across a hepatobiliary network.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":6},{"id":"idea-bio2-mrd-clinic-service","kind":"idea","name":"A dedicated clinic for people whose blood test says the cancer is back","aka":[],"tldr":"A positive leftover-cancer blood test leaves patients frightened and their doctors unsure what to do. A specialist clinic could give them a plan and a trial.","summary":"The molecular relapse population is growing fast and falls between services: no visible disease, no standard therapy, high anxiety and low trial awareness. A named clinic (confirmatory retesting, sensitive imaging, psychological support, trial screening and structured follow-up) is a service-design intervention that could be evaluated like any other pathway.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Dormant cells and minimal residual disease): Tie et al., ctDNA analysis guiding adjuvant therapy in stage II colon cancer (NEJM 2022)","url":"https://doi.org/10.1056/NEJMoa2200075"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["mrd-testing","ai-trial-matching"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["mrd"],"trials":[],"people":[],"bottlenecks":["b-dormancy-mrd","b-care-fragmentation","b-patient-voice"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A dedicated molecular relapse clinic increases trial enrolment among ctDNA-positive patients threefold and reduces anxiety scores compared with usual follow-up, with no increase in cost per patient once inappropriate imaging is avoided.","rationale":"Analogous focused services (rapid diagnostic centres, cancer of unknown primary clinics, cardio-oncology) improved both pathway metrics and enrolment. The bottleneck for MRD trials is not eligibility but the absence of anyone whose job it is to act on the result.","test":"Two-centre service pilot with pre-specified metrics: time from positive result to plan, trial enrolment rate, imaging use, patient-reported anxiety at three months.","maturity":"speculative","actor":"clinic","cost":"small","horizonYears":3},{"id":"idea-data-prospective-ai-trials-fund","kind":"idea","name":"A dedicated fund for randomised trials of cancer AI with patient outcomes","aka":[],"tldr":"Thousands of cancer AI tools have been tested on old data; almost none in a proper trial. Fund the trials, with endpoints that matter to patients.","summary":"Systematic reviews find that fewer than a few percent of published oncology AI models have prospective evaluation and vanishingly few have randomised trials with clinical endpoints. Exceptions such as the MASAI mammography screening trial in Sweden show the design is feasible and informative. The proposal is a public and philanthropic fund that pays for pragmatic randomised trials of AI tools in pathology, radiology, screening and decision support, requiring pre-registration, clinical endpoints (cancer detection rate, interval cancers, time to treatment, survival) and open reporting.","asOf":"2026-09-08","links":[{"label":"MASAI trial (Lancet Oncology 2023)","url":"https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(23)00298-X/fulltext"}],"tags":[],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":["radiology-ai-screening","digital-pathology-ai","mammography"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-ai-validation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Randomised evaluation will show that a minority of AI tools with strong retrospective performance improve patient-relevant outcomes, and the resulting evidence will drive adoption of those that do and retirement of those that do not.","rationale":"Retrospective accuracy has repeatedly failed to translate into benefit in other digital health interventions; only randomisation resolves the question, and the MASAI trial shows it can be done at scale within a screening programme.","test":"Fund ten pragmatic randomised trials of deployed or near-deployed cancer AI tools over five years; report how many show benefit, harm or no effect.","maturity":"early-clinical","actor":"philanthropy","cost":"large","horizonYears":4},{"id":"idea-acc-global-cancer-financing-window","kind":"idea","name":"A dedicated global financing window for cancer, modelled on the Global Fund","aka":[],"tldr":"Cancer kills more people in poorer countries than HIV, TB and malaria combined, but has no global fund. A pooled fund for diagnosis, essential medicines and radiotherapy would change what ministries can afford to build.","summary":"Development assistance for health has largely bypassed cancer. Despite rising burden in LMICs, there is no multilateral financing instrument for cancer services comparable to the Global Fund or Gavi. A financing window, whether a new fund or a cancer envelope inside an existing one, would co-finance national cancer control plans with conditions on registries, essential medicine availability, and palliative care. The design questions are governance, co-financing ratios, and how to avoid crowding out domestic spending.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Most of the world has almost no cancer care): WHO fact sheet, Cancer","url":"https://www.who.int/news-room/fact-sheets/detail/cancer"}],"tags":[],"related":["globocan"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["iarc"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-global-access","b-funding-allocation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Countries receiving co-financing tied to a costed national cancer plan will increase the proportion of patients receiving any cancer treatment by at least 50% within six years, measured through population-based registries.","rationale":"The Global Fund and Gavi showed that predictable, results-linked external finance plus technical assistance builds durable programmes; cancer control has the same structure of high fixed costs and long payback.","test":"A five-country pilot envelope with published disbursements, registry-based outcome tracking, and an independent evaluation against matched non-recipient countries.","maturity":"speculative","actor":"policy","cost":"large","horizonYears":6},{"id":"idea-fund-cachexia-programme","kind":"idea","name":"A dedicated programme for cachexia and treatment toxicity research","aka":[],"tldr":"Wasting and side-effects kill or stop treatment for a large share of patients but attract almost no dedicated funding. This would create a standing programme for them.","summary":"A programme with its own review panel funds cachexia mechanisms (GDF15, inflammatory and neural circuits), interventional trials of anti-cachexia agents and nutrition and exercise bundles, and toxicity science (neuropathy, cardiotoxicity, cytopenias, cognitive effects) with biomarkers and prevention trials. Supportive-care research fails in general panels because it is judged as less innovative; a dedicated pot and reviewers who know the field fixes that. GDF15 antagonists reaching late-phase trials show the biology is tractable.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Funding follows fashion, not burden): Carter & Nguyen, A comparison of cancer burden and research spending (BMC Cancer 2012)","url":"https://doi.org/10.1186/1471-2407-12-526"}],"tags":[],"related":["idea-fund-ten-year-hard-problem-awards","idea-exercise-as-adjuvant"],"cancers":[],"sections":[],"technologies":["exercise-oncology","cardio-oncology","geriatric-assessment","scalp-cooling"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-funding-allocation","b-cachexia-supportive","b-toxicity-qol"],"keyPapers":["paper-sun-bmc-cancer"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A dedicated programme at 2% of a national budget doubles registered interventional trials in cachexia and toxicity within five years and yields at least one approved supportive-care agent or validated toxicity-prevention strategy within ten.","rationale":"Cachexia is implicated in up to a third of cancer deaths; the recent progress on GDF15 came from industry, not academia, because academic supportive-care research was starved. Dedicated programmes created fields in palliative care in the UK and in geriatric oncology in France.","test":"Portfolio audit, then launch and compare trial registrations, publications and industry co-investment in the supported area after five years with a matched neglected area.","maturity":"speculative","actor":"philanthropy","cost":"medium","horizonYears":5},{"id":"idea-acc-dementia-and-cancer-pathway","kind":"idea","name":"A defined pathway for patients with both dementia and cancer","aka":[],"tldr":"People with dementia who develop cancer are often either overtreated or written off, and decisions are made without them. A clear pathway for assessment, consent and treatment planning would improve both.","summary":"Dementia is common among older cancer patients and complicates diagnosis, capacity assessment, consent, adherence, and toxicity recognition. There is little guidance. A pathway combining cognitive screening at diagnosis, structured capacity assessment, involvement of carers and, where appropriate, advance care planning, simplified regimens, and supported adherence would reduce both undertreatment of those who could benefit and harmful treatment of those who cannot.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Older and multimorbid patients are excluded and undertreated): Mohile et al., Evaluation of geriatric assessment and management on toxic effects of cancer treatment (GAP70+, Lancet 2021)","url":"https://doi.org/10.1016/S0140-6736(21)01789-X"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["geriatric-assessment"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-aging-comorbidity","b-patient-voice","b-care-fragmentation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Patients with dementia managed through a defined pathway will show higher rates of documented capacity assessment and goal-concordant treatment, and fewer emergency admissions during treatment.","rationale":"Comorbid dementia is a growing group with no evidence base; pathway approaches have improved care in hip fracture and delirium.","test":"Develop and pilot the pathway in five centres, measuring documentation of capacity and goals, treatment decisions, and admissions against historical controls.","maturity":"speculative","actor":"clinic","cost":"small","horizonYears":3},{"id":"idea-reg-delinked-market-entry-reward","kind":"idea","name":"A delinked market-entry reward paid by payers when a repurposed generic wins approval","aka":[],"tldr":"Instead of letting a company charge more for a newly proven use of an old drug, payers would pay a one-off reward and keep the price low for everyone.","summary":"Delinked rewards separate the return on R&D from the price of the product; they have been proposed and partly implemented for antibiotics (UK subscription, PASTEUR Act proposals). For repurposing, the proposal is a pre-announced reward (for example $30-100 million depending on the size of benefit) paid by a consortium of payers to the sponsor of a positive registration-quality trial of an off-patent drug in cancer, conditional on the label being updated and the price remaining at generic levels. Payers benefit because the drug remains cheap while the incentive to run the trial exists.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (No incentive to repurpose cheap drugs): Pantziarka et al., The Repurposing Drugs in Oncology (ReDO) Project (ecancer 2014)","url":"https://doi.org/10.3332/ecancer.2014.442"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-generic-repurposing","b-drug-pricing"],"keyPapers":["paper-pantziarka-ecancermedicalscience"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A published reward schedule induces at least five registration-quality repurposing trials within five years and delivers proven indications at generic prices, saving payers more than the rewards paid.","rationale":"Where the product is already cheap, the efficient way to fund evidence is to pay for the evidence directly rather than through monopoly pricing; the reward can be tied to the magnitude of benefit shown.","test":"Have three or four national payers commit to a reward pool and announce criteria; track trial registrations, completions and label updates over five years.","maturity":"speculative","actor":"payer","cost":"large","horizonYears":5},{"id":"idea-fund-prevention-moonshot","kind":"idea","name":"A delivery-science moonshot for prevention we already own","aka":[],"tldr":"Around four in ten cancers are preventable with tools that exist now. This would fund the hard, unglamorous work of getting vaccines, screening and tobacco control to everyone, paid on results.","summary":"An ARPA-style programme, but for implementation: it funds and rigorously evaluates ways to reach 90% HPV and hepatitis B vaccine coverage, H. pylori test-and-treat in high-incidence populations, tobacco cessation embedded in lung screening, and alcohol and obesity policy trials. Payments are milestone- and outcome-based (coverage achieved, quitters verified) rather than for papers. The scientific content is behavioural economics, health-systems engineering and policy evaluation, which conventional cancer funders rarely score well.","asOf":"2026-09-08","links":[{"label":"WHO cervical cancer elimination initiative","url":"https://www.who.int/initiatives/cervical-cancer-elimination-initiative"},{"label":"ARPA-H","url":"https://arpa-h.gov/"}],"tags":[],"related":["idea-fund-social-impact-bonds-prevention"],"cancers":["cervical","hcc","gastric","nsclc"],"sections":[],"technologies":["hpv-vaccine","chemoprevention","radiology-ai-screening"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-funding-allocation","b-prevention-adoption"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A prevention-delivery programme funded at 5% of a national cancer research budget, paying on verified coverage outcomes, lifts HPV vaccine completion and lung-screening uptake in target populations by at least 15 percentage points within five years, at a cost per life-year saved below that of any recently approved oncology drug.","rationale":"Modelling for the WHO cervical cancer elimination strategy shows vaccination plus screening eliminates a cancer within a lifetime; the constraint is delivery, not knowledge. Outcome-based funding has moved coverage in vaccination (Gavi performance-based financing) and in tuberculosis case-finding.","test":"Cluster-randomised implementation trials in three regions comparing outcome-paid delivery contracts with standard grant funding for HPV catch-up and lung screening, measuring coverage and cost per additional person covered after two years.","maturity":"speculative","actor":"policy","cost":"large","horizonYears":5},{"id":"idea-nl-dietitian-in-every-mdt","kind":"idea","name":"A dietitian in every gastrointestinal and head and neck tumour board","aka":[],"tldr":"Malnutrition is the commonest untreated complication in cancers of the gut, throat and pancreas. Putting a dietitian in the meeting where treatment is decided means it is seen and treated before chemotherapy starts, not after weight has been lost.","summary":"Guidelines require malnutrition screening at diagnosis, and trials show dietitian counselling improves treatment completion in head and neck and gastrointestinal cancers, yet audits find fewer than half of patients are screened and dietitian referral typically follows, rather than precedes, treatment. Embedding a dietitian in the multidisciplinary team meeting for upper GI, pancreatic, colorectal and head and neck cancer, with authority to initiate nutrition therapy, prehabilitation and enzyme replacement, is a service-design change with a plausible effect on dose intensity and surgical complications.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Cachexia, toxicity and the limits of the patient): Fearon et al., Definition and classification of cancer cachexia (Lancet Oncology 2011)","url":"https://doi.org/10.1016/S1470-2045(10)70218-7"}],"tags":[],"related":["idea-bio2-cachexia-pathway-code","idea-moon-geriatric-assessment-default"],"cancers":["head-and-neck","esophageal","gastric","pancreatic","colorectal"],"sections":["nutrition-lifestyle","supportive-care"],"technologies":["nutrition-screening-mnt","oncology-nutrition","eras-perioperative-nutrition","geriatric-assessment"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["malnutrition-screening","nutrition-impact-symptoms","cachexia"],"trials":[],"people":[],"bottlenecks":["b-cachexia-supportive","b-workforce","b-care-fragmentation"],"keyPapers":["paper-fearon-lancet-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Dietitian participation in tumour boards with a nutrition plan for every patient increases the proportion of malnourished patients treated before first therapy from under 30% to over 80% and raises completion of planned chemotherapy or chemoradiation by at least 10 percentage points.","rationale":"The intervention is cheap relative to the cost of treatment interruptions and readmissions, the workforce (one dietitian per team) is realistic, and the geriatric assessment literature shows that structured assessment attached to the treatment decision changes outcomes.","test":"Stepped-wedge cluster trial across 20 hospitals with screening rate, time to nutrition intervention, relative dose intensity, unplanned admissions and 1-year survival as endpoints, plus cost analysis; then guideline and commissioning change.","maturity":"early-clinical","actor":"clinic","cost":"medium","horizonYears":3},{"id":"idea-tr2-cell-line-passport","kind":"idea","name":"A digital passport for every cell culture: identity, contamination status, passage number","aka":[],"tldr":"Each batch of cells used in an experiment would carry a small digital record showing when it was authenticated, tested for contamination, and how many times it had been grown, attached to the published result.","summary":"Beyond identity, mycoplasma contamination and high passage number change cell behaviour and drug sensitivity. A lightweight standard (a signed JSON record with STR match, mycoplasma test date, passage, source and thaw date) generated by lab inventory software and attached to figures or methods as a persistent identifier would make culture provenance auditable and enable meta-analyses of how provenance affects results.","asOf":"2026-09-08","links":[{"label":"Cellosaurus","url":"https://www.cellosaurus.org/"}],"tags":[],"related":["idea-tr2-cell-line-authentication-mandate","idea-tr2-reagent-lot-ledger"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-reproducibility","b-preclinical-models"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Papers with passports will show higher replication rates in subsequent independent studies than those without, and passport data will reveal passage-dependent drug-sensitivity shifts in commonly used lines.","rationale":"Provenance metadata standards (for sequencing runs, for reagents) improved reproducibility where adopted; cell culture lacks one.","test":"Implement the standard in two open-source lab inventory tools; pilot in ten labs; audit reproducibility of a sample of results with and without passports.","maturity":"speculative","actor":"engineering","cost":"small","horizonYears":2},{"id":"idea-data-72-hour-second-opinion-network","kind":"idea","name":"A digital second-opinion network answering community oncologists within 72 hours","aka":[],"tldr":"Any oncologist could send a difficult case, with the records, to a specialist centre and get a written expert opinion back within three days, free to the patient.","summary":"Expertise is concentrated in a few centres; most patients are treated elsewhere. Asynchronous e-consultation (as in Project ECHO and tele-tumour boards) works but is patchy. The proposal is a funded national network with a standard case bundle (patient-held record or mCODE export), triage to the right subspecialist, a 72-hour written opinion, structured recording of the recommendation, and outcome follow-up to measure impact.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Knowledge reaches practice too slowly): Morris, Wooding & Grant, The answer is 17 years, what is the question (JRSM 2011)","url":"https://doi.org/10.1258/jrsm.2011.110180"}],"tags":[],"related":["idea-data-patient-held-cancer-record"],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-knowledge-diffusion","b-care-fragmentation","b-rare-cancers"],"keyPapers":["paper-morris-j-r-soc-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Rapid second opinions will change management in a substantial minority of referred cases and will be associated with higher guideline concordance and trial referral.","rationale":"Second-opinion studies in pathology and oncology find management changes in a significant share of cases; speed and structured data are what make the model scalable.","test":"Run the network for one year in one region; report turnaround, proportion of opinions changing management, and trial referrals; compare guideline concordance with non-referred matched cases.","maturity":"early-clinical","actor":"clinic","cost":"medium","horizonYears":2},{"id":"idea-fund-royalty-pool-academic-assets","kind":"idea","name":"A diversified royalty pool that finances academic phase 1 trials across fifty assets","aka":[],"tldr":"Investors will not back a single university drug because most fail. A fund that finances fifty of them at once in exchange for a small slice of each one's future royalties spreads the risk enough to attract capital.","summary":"A financing vehicle, modelled on Royalty Pharma and the research-backed obligation proposals of Andrew Lo and colleagues, that funds IND-enabling and phase 1 costs for a large portfolio of academic oncology assets in return for a percentage of future licensing revenue on each. Diversification across many uncorrelated assets makes the expected return investable even at high individual failure rates. Universities contribute assets and receive most of the upside; the pool handles project management through the translational institutes and non-profit CRO. Portfolio size is the key variable and would be set by modelling with real attrition data.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The valley of death between lab and product): Butler, Translational research: crossing the valley of death (Nature 2008)","url":"https://doi.org/10.1038/453840a"}],"tags":[],"related":["idea-fund-sovereign-first-in-class-coinvestment","idea-fund-ind-enabling-fund","idea-fund-milestone-venture-philanthropy"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-translational-valley","b-incentive-misalignment"],"keyPapers":["paper-butler-nature"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A pool of fifty academic assets financed to phase 1 produces licensing revenue sufficient to return investors' capital within twelve years in the base case, and doubles the proportion of academic oncology assets reaching phase 1 in participating universities.","rationale":"Lo's megafund analysis shows that portfolios of 50 to 150 early assets can achieve investment-grade risk profiles; Royalty Pharma's model demonstrates appetite for royalty streams; university tech transfer income is highly concentrated in a few winners, which is exactly the distribution diversification exploits.","test":"Model with historical academic attrition and licensing data, then raise a pilot pool of $200 million across twenty universities and report progression and revenue at years five and ten.","maturity":"speculative","actor":"industry","cost":"large","horizonYears":5},{"id":"idea-nl-exercise-dose-finding","kind":"idea","name":"A dose-finding trial for exercise after cancer","aka":[],"tldr":"CHALLENGE proved exercise works in colon cancer but not how much is needed. A trial comparing doses, as we would for a drug, would tell health systems what to fund.","summary":"Drugs get dose-finding; exercise got a single dose (about 10 MET-hours/week above baseline) chosen from cohort data. Cohorts suggest a dose-response with benefit continuing beyond 18 MET-hours/week, but also that the first few hours matter most. Health systems deciding what to reimburse need to know whether a cheaper, lower-dose or unsupervised programme retains most of the benefit.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Survivorship and late effects are neglected): NCI Office of Cancer Survivorship statistics","url":"https://cancercontrol.cancer.gov/ocs/statistics"}],"tags":[],"related":["idea-exercise-as-adjuvant","idea-bio2-exercise-reimbursement"],"cancers":["colorectal","breast-hr-positive"],"sections":["nutrition-lifestyle"],"technologies":["structured-exercise-survivorship","exercise-oncology"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["met-hours","energy-balance"],"trials":["challenge"],"people":[],"bottlenecks":["b-survivorship","b-trial-design","b-prevention-adoption"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"In colon or breast cancer survivors, disease-free survival improves in a dose-dependent manner across 5, 10 and 20 MET-hours/week of supervised activity, with most of the benefit achieved at 10 MET-hours/week, and objectively measured adherence (wearables) rather than prescribed dose predicts outcome.","rationale":"Dose-response evidence converts a single positive trial into a prescribable intervention, defines the minimum effective dose for resource-limited settings, and lets wearables substitute for self-report as the exposure measure.","test":"Three-arm randomised trial (n about 1,500) in stage II-III colon cancer after adjuvant chemotherapy with wearable-verified MET-hours, DFS primary endpoint, embedded cost-effectiveness and a biomarker sub-study (insulin, CRP, ctDNA).","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":6},{"id":"idea-bio2-dormancy-selective-screen","kind":"idea","name":"A drug screen that only rewards killing sleeping cancer cells","aka":[],"tldr":"Nearly all cancer drugs are found by killing fast-growing cells. Sleeping cells survive them. A screen designed around dormant cells would find a different class of drug.","summary":"Dormant disseminated tumour cells are non-cycling, so proliferation-based screens are blind to them. Induced-dormancy models exist (serum-starved and matrix-confined cells, bone-marrow-niche co-cultures, three-dimensional dormancy assays) and small screens have already flagged cardiac glycosides, autophagy inhibitors and specific metabolic dependencies. Nobody has run a million-compound campaign with dormancy-selective killing as the primary readout.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Dormant cells and minimal residual disease): Tie et al., ctDNA analysis guiding adjuvant therapy in stage II colon cancer (NEJM 2022)","url":"https://doi.org/10.1056/NEJMoa2200075"}],"tags":[],"related":["depmap","drugbank-chembl"],"cancers":[],"sections":[],"technologies":["organoids","functional-drug-testing","crispr-screens"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-dormancy-mrd","b-preclinical-models","b-undruggable-targets"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A dormancy-selective screen yields compounds that kill non-cycling disseminated tumour cells at least ten times more potently than cycling cells, a selectivity profile absent from current oncology libraries.","rationale":"Screening paradigm determines drug class: kinase inhibitors dominate because proliferation assays reward them. Anti-persister screening in bacteriology produced genuinely new antibiotic chemistry by the same logic.","test":"Build and openly publish a validated dormancy assay pair (dormant versus cycling isogenic cells), screen an approved-drug library plus 100,000 diverse compounds, and report all hit and miss data.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":6},{"id":"idea-reg-generic-targeted-therapy-drup","kind":"idea","name":"A DRUP-style protocol for off-label generic targeted drugs in rare tumours","aka":[],"tldr":"Cheap generic versions of targeted cancer drugs like imatinib exist, but patients with rare tumours carrying the matching mutation often cannot get them. A structured programme would treat them and collect the evidence.","summary":"The Netherlands' Drug Rediscovery Protocol (DRUP) gives patients with actionable mutations access to approved targeted drugs outside their label, with cohorts expanding on response and payers covering successful cohorts; it has been replicated in several countries. Now that imatinib, erlotinib, gefitinib, sunitinib, abiraterone and others are generic, an analogous protocol for generic targeted drugs would be extremely cheap. The proposal is a DRUP-generic arm run across countries including middle-income ones, with genomic profiling, cohort-based Simon two-stage designs, and pre-agreed payer coverage for cohorts meeting response thresholds.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (No incentive to repurpose cheap drugs): Pantziarka et al., The Repurposing Drugs in Oncology (ReDO) Project (ecancer 2014)","url":"https://doi.org/10.3332/ecancer.2014.442"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["kinase-inhibitors","cgp"],"targets":[],"drugs":["imatinib"],"companies":[],"institutions":["nki"],"pathways":[],"terms":["basket-umbrella-platform"],"trials":[],"people":[],"bottlenecks":["b-generic-repurposing","b-rare-cancers"],"keyPapers":["paper-pantziarka-ecancermedicalscience"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"At least 20% of generic drug-mutation cohorts reach the pre-specified response threshold and gain routine coverage, treating patients with rare tumours at a drug cost under $2,000 per year.","rationale":"DRUP has shown that a third of off-label cohorts show clinical benefit; with generic drugs the cost-effectiveness is almost guaranteed for any cohort that responds, and the evidence gap is the only barrier.","test":"Open ten generic drug cohorts across five countries with a common protocol; report response rates, coverage decisions and cost per responder at three years.","maturity":"early-clinical","actor":"clinic","cost":"medium","horizonYears":3},{"id":"idea-fund-ind-enabling-fund","kind":"idea","name":"A fast IND-enabling fund that pays for toxicology and manufacturing in eight weeks","aka":[],"tldr":"The studies needed before a first human trial cost a few million and no grant pays for them. A dedicated fund would decide in weeks and take a small share of any future revenue.","summary":"A revolving fund, capitalised by philanthropy and public money, that pays for GLP toxicology, CMC development, formulation and regulatory writing for academic oncology candidates that have passed independent replication of the efficacy result the candidate rests on. Decisions in eight weeks by a standing expert panel; awards of $2 to $8 million; in return the fund takes a low single-digit royalty or a share of licensing revenue, recycled into the fund. Structured like the Wellcome Trust's Seeding Drug Discovery or the Michael J. Fox Foundation's therapeutic pipeline programme, but oncology-focused and paired with the translational institutes. Most academic assets stall exactly here because IND-enabling work is neither science (so not fundable by grants) nor de-risked enough for companies.","asOf":"2026-09-08","links":[{"label":"Wellcome Trust","url":"https://wellcome.org/"}],"tags":[],"related":["idea-fund-replication-set-aside","idea-fund-translational-institutes-gmp","idea-fund-milestone-venture-philanthropy"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-translational-valley"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A fund of $100 million enables at least twenty academic oncology candidates to file INDs within four years, of which at least a quarter are licensed or reach phase 2, with royalty and licensing returns covering more than a third of disbursements over ten years.","rationale":"Seeding Drug Discovery and similar translational funds report that a substantial fraction of supported programmes attract industry partners; the Cystic Fibrosis Foundation's programme returned billions from a comparable model. Speed matters because academic teams disperse and competitors move on during multi-year funding delays.","test":"Capitalise a pilot at $20 million, fund ten candidates with the eight-week process, and track INDs filed, licensing and time-to-decision against a historical academic cohort.","maturity":"speculative","actor":"philanthropy","cost":"medium","horizonYears":3},{"id":"idea-bio1-mechanism-matched-access","kind":"idea","name":"A fast route to the matched drug when it is licensed for another cancer","aka":[],"tldr":"Sometimes a progression biopsy shows exactly which drug would help, but it is licensed for another cancer and cannot be obtained. A standing pathway would fix that.","summary":"Mechanism-matched treatment recommendations frequently fail at the access step. A national pathway modelled on the Dutch DRUP and UK-style access schemes would combine a molecular tumour board decision, company-supplied drug, mandatory outcome registration and payer participation, so that every off-label use generates evidence. This converts scattered compassionate use into a structured cohort study.","asOf":"2026-09-08","links":[{"label":"DRUP trial (NCT02925234)","url":"https://clinicaltrials.gov/study/NCT02925234"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["nki"],"pathways":[],"terms":["tumour-agnostic","real-world-evidence"],"trials":[],"people":[],"bottlenecks":["b-resistance","b-generic-repurposing","b-regulatory-fragmentation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A standing mechanism-matched access pathway raises the proportion of actionable resistance findings that result in treatment from a small minority to over half, and generates interpretable efficacy data per mechanism-drug pair.","rationale":"DRUP-type studies have shown that structured off-label access with outcome collection is feasible and produces usable evidence for rare biomarker-drug combinations.","test":"Launch a pathway in one country covering ten drugs for three years; measure treatment rate for actionable findings, response rates by cohort, and time from report to first dose.","maturity":"speculative","actor":"regulator","cost":"medium","horizonYears":4},{"id":"idea-pdac-uk-fast-track-diagnosis-to-treatment-pathway","kind":"idea","name":"A fast-track pathway from suspicion to treatment for pancreatic cancer in the NHS, measured from first scan to first treatment","aka":[],"tldr":"Pancreatic cancer grows and spreads quickly, and delays between the scan that finds it, the specialist meeting, the biopsy, the bile duct stent and the first chemotherapy or operation are measured in weeks. The proposal is a dedicated fast-track pathway with a national standard for the interval from first imaging to first treatment, reported by the audit.","summary":"The National Pancreatic Cancer Audit reports intervals along the pathway (referral, diagnosis, multidisciplinary discussion, treatment) and the proportion treated; Pancreatic Cancer UK has campaigned for treatment within a set number of weeks of diagnosis. The clinical logic is that biliary obstruction must be relieved before chemotherapy (stent), tissue is needed before systemic treatment, and fitness declines while patients wait, so a pathway that runs staging CT, endoscopic ultrasound with biopsy and stenting, germline and tumour testing, dietetic and enzyme assessment and the specialist meeting in parallel within a fixed window is what shortens the interval. This is a placeholder for the specific UK figures and targets the UK and NHS page carries; the idea here is the measurement: adopt first imaging to first treatment as the audited interval, set a national standard, and test whether pathway redesign in a region shortens it without lowering the treatment rate.","asOf":"2026-09-24","links":[{"label":"National Pancreatic Cancer Audit (NPaCA)","url":"https://www.natcan.org.uk/audits/pancreatic/"},{"label":"Pancreatic Cancer UK: Unite Diagnose Save Lives 2025 open letter","url":"https://www.pancreaticcancer.org.uk/get-involved/take-action/join-our-campaigns/unite-diagnose-save-lives-2025/"},{"label":"NICE NG85: pancreatic cancer in adults (2018)","url":"https://www.nice.org.uk/guidance/ng85"}],"tags":["pancreatic-evidence"],"related":["idea-pdac-uk-active-treatment-rate-audit-and-target","idea-pdac-new-onset-diabetes-risk-score-pathway"],"cancers":["pancreatic"],"sections":[],"technologies":["ct","germline-testing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["obstructive-jaundice","biliary-stent","performance-status"],"trials":[],"people":[],"bottlenecks":["b-care-fragmentation","b-early-detection"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A parallel-process fast-track pathway reduces the median interval from first imaging showing a pancreatic mass to first treatment by at least two weeks and raises the proportion of patients fit for combination chemotherapy at the start of treatment.","rationale":"Every week of delay in a cancer with a median untreated survival of a few months matters; the steps are known and can be scheduled together; the audit can measure the interval nationally.","test":"Regional stepped-wedge implementation with the audit's pathway intervals as outcomes, treatment rate and performance status at first treatment as safety and secondary measures.","maturity":"speculative","actor":"policy","cost":"medium","horizonYears":4},{"id":"idea-fund-federated-learning-consortium","kind":"idea","name":"A federated learning consortium of cancer centres that jointly own the models","aka":[],"tldr":"Hospitals could train shared AI models on all their patients' scans and records without any data leaving the building, and jointly own the results, if someone built and governed the network.","summary":"A consortium of cancer centres and trial groups operating a federated learning infrastructure (models travel, data stay) for pathology, radiology and multimodal outcome prediction, with a governance agreement that gives members joint ownership of trained models, shared validation protocols and a route to regulatory submission. Owkin's federated networks and the EU's several federated health data projects show technical feasibility; the missing piece is a durable, member-owned institution with IP terms that reward data contribution rather than data extraction. Prospective validation of consortium models in member trials closes the loop with the AI validation bottleneck.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Secrecy and intellectual property block collaboration): Danchev et al., Evaluation of data sharing after implementation of the ICMJE data sharing statement requirement (JAMA Netw Open 2021)","url":"https://doi.org/10.1001/jamanetworkopen.2020.33972"}],"tags":[],"related":["idea-multimodal-foundation-model","idea-fund-trial-data-trust"],"cancers":[],"sections":[],"technologies":["digital-pathology-ai","pathology-foundation-model","radiology-ai-screening"],"targets":[],"drugs":[],"companies":["owkin"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-ip-collaboration","b-data-silos","b-ai-validation"],"keyPapers":["paper-danchev-jama-netw-open"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A member-owned federated consortium of twenty centres trains models that outperform single-centre models on held-out external validation for at least three clinical tasks within three years, and at least one consortium model enters a prospective clinical trial.","rationale":"Federated training has matched centralised training in published pathology and radiology tasks; the barrier to scale is governance and IP, not algorithms. Member ownership addresses the concern that centres give away data value to vendors.","test":"Constitute the consortium with a governance charter, run three federated training tasks against single-centre baselines and pre-register external validation.","maturity":"early-clinical","actor":"engineering","cost":"medium","horizonYears":3},{"id":"idea-fund-implementation-quota","kind":"idea","name":"A fixed share of trial-group funding for getting proven care to patients","aka":[],"tldr":"Proven treatments, genomic tests and timely referrals routinely fail to reach the patients who qualify for them. Public trial networks such as the NCTN groups, EORTC and the UK NIHR portfolio would have to spend at least 10% of their funding on cluster-randomised or stepped-wedge trials of how to close that gap, cheap studies that use routine data.","summary":"Public trial networks (the NCTN groups, EORTC, UK NIHR portfolio) would be required to allocate at least 10% of funding to implementation trials: cluster-randomised or stepped-wedge studies of how to raise guideline-concordant care, genomic testing rates, timely referral, geriatric assessment and survivorship follow-up. These trials are cheap per patient, use routine data and address a gap that observational studies put at tens of thousands of avoidable deaths a year in high-income countries alone.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Funding follows fashion, not burden): Carter & Nguyen, A comparison of cancer burden and research spending (BMC Cancer 2012)","url":"https://doi.org/10.1186/1471-2407-12-526"}],"tags":[],"related":["nccn","esmo-guidelines","idea-fund-payer-funded-pragmatic-trials"],"cancers":[],"sections":[],"technologies":["geriatric-assessment","cgp"],"targets":[],"drugs":[],"companies":["swog","ecog-acrin","curie-nki-eortc"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-funding-allocation","b-care-fragmentation"],"keyPapers":["paper-sun-bmc-cancer"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Trial networks that spend 10% on implementation trials increase guideline-concordant care for at least two measurable indicators (for example biomarker testing before first-line therapy, adjuvant therapy completion) by 10 percentage points in participating regions within four years.","rationale":"Implementation science has a track record in cardiovascular medicine (statin and blood-pressure programmes) and in HIV; in oncology, the gap between proven and delivered care is well documented but seldom the object of a funded trial because no drug sponsor benefits.","test":"One network runs the quota for a full funding cycle and compares indicator improvement and cost per additional patient correctly treated with a matched network that does not.","maturity":"speculative","actor":"policy","cost":"medium","horizonYears":4},{"id":"idea-fund-patient-burden-review-criterion","kind":"idea","name":"A formal patient-burden score in grant peer review","aka":[],"tldr":"Add a scored criterion to grant review that asks how much suffering the proposal addresses and how soon, judged partly by patients, and give it real weight.","summary":"Peer review currently scores significance, innovation and approach, which reward novelty and technical elegance. A burden criterion (deaths, DALYs and unmet need in the target population, plausible time to patient impact) is scored separately by a panel that includes trained patient reviewers and carries 20% of the total. The Patient-Centered Outcomes Research Institute and the US Department of Defense cancer programmes already include consumer reviewers; this makes burden an explicit, weighted term.","asOf":"2026-09-08","links":[{"label":"CDMRP (US DoD medical research programmes)","url":"https://cdmrp.health.mil/"}],"tags":[],"related":["idea-fund-burden-weighted-portfolio","idea-fund-portable-patient-consent"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-funding-allocation","b-patient-voice"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Introducing a 20% burden criterion shifts the funded portfolio towards high-burden, near-term questions within two cycles without lowering the mean scientific quality score of funded awards.","rationale":"Where consumer reviewers sit on panels (DoD CDMRP, PCORI) funded portfolios differ measurably from science-only panels, and investigators report designing more patient-relevant studies. Explicit weights are needed because informal patient input is discounted when it conflicts with scientific enthusiasm.","test":"Score one review round twice, with and without the burden criterion, and compare the two hypothetical funded sets on burden alignment and scientific score; then run it live for a cycle.","maturity":"speculative","actor":"policy","cost":"small","horizonYears":2},{"id":"idea-tr2-prospective-retrospective-path","kind":"idea","name":"A formal regulatory route for validating a biomarker on archived trial samples","aka":[],"tldr":"Completed trials have stored samples. Testing a new biomarker on them with the plan written in advance is nearly as good as a new trial and far cheaper, but regulators have no clear route to accept it.","summary":"The prospective-retrospective design (Simon, Paik and Hayes) uses archived samples from a completed randomised trial with a pre-specified analysis plan to validate a predictive biomarker. It rescued KRAS testing for anti-EGFR antibodies and Oncotype DX. Regulators accept it case by case. A published guidance with requirements (sample availability above a threshold, pre-registered analysis plan, independent statistical execution) would make the route predictable and encourage sponsors to bank and share samples.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Biomarkers are not validated or standardised): Fernandez et al., Examination of low ERBB2 protein expression in breast cancer tissue (JAMA Oncology 2022)","url":"https://doi.org/10.1001/jamaoncol.2021.7239"}],"tags":[],"related":["idea-tr2-failed-trial-biobank","tailorx","rxponder"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":["oncotype-dx"],"companies":[],"institutions":[],"pathways":[],"terms":["companion-diagnostic-term"],"trials":[],"people":[],"bottlenecks":["b-biomarker-validation","b-negative-results"],"keyPapers":["paper-fernandez-jama-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Guidance will double the number of biomarker label changes supported by prospective-retrospective analyses within five years and cut the average time from biomarker hypothesis to label from six years to three.","rationale":"The design is accepted in the methodological literature and has produced several practice changes; the barrier is regulatory uncertainty and sample access.","test":"Draft and publish guidance; track submissions and outcomes; compare with the preceding five years.","maturity":"early-clinical","actor":"regulator","cost":"small","horizonYears":2},{"id":"idea-moon-lynch-vaccine-phase3","kind":"idea","name":"A frameshift neoantigen vaccine for Lynch syndrome carriers as the first preventive cancer vaccine approval","aka":[],"tldr":"People with Lynch syndrome have a very high lifetime cancer risk from a predictable set of mutations. Vaccinate them against those shared mutations before cancer appears.","summary":"Mismatch repair deficiency produces recurrent frameshift neoantigens shared across Lynch-associated tumours, and pilot vaccines have shown immunogenicity in carriers and in mice reduced tumour incidence. The proposal is to take a multi-epitope frameshift vaccine (mRNA or viral vector, possibly with a checkpoint-sparing adjuvant) into a randomised prevention trial in carriers with a surrogate endpoint of adenoma and early-cancer incidence at colonoscopy, positioning it as the first preventive cancer vaccine registration for a hereditary syndrome.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Inherited risk is mostly unidentified): Childers et al., National estimates of genetic testing in women with breast or ovarian cancer (JCO 2017)","url":"https://doi.org/10.1200/JCO.2017.73.6314"}],"tags":[],"related":["idea-interception-vaccines"],"cancers":["colorectal","endometrial"],"sections":[],"technologies":["shared-antigen-vaccine","neoantigen-mrna-vaccine"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["msi","neoantigen"],"trials":[],"people":[],"bottlenecks":["b-hereditary-risk","b-prevention-adoption"],"keyPapers":["paper-childers-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Vaccination reduces incident advanced adenomas and cancers in Lynch carriers by at least 40% over five years compared with surveillance alone.","rationale":"Predictable shared antigens, a defined high-risk population with regular endoscopic surveillance providing a fast surrogate, and mature vaccine platforms make this the most tractable preventive vaccine in oncology.","test":"Phase 2b/3 randomised placebo-controlled trial in about 1,500 carriers with colonoscopy-based endpoints; interim immunological and adenoma readouts at two years.","maturity":"early-clinical","actor":"research","cost":"large","horizonYears":8},{"id":"idea-tr2-hrd-functional-standard","kind":"idea","name":"A functional test for homologous recombination deficiency validated across laboratories","aka":[],"tldr":"Tests for 'HRD', which decide who gets PARP inhibitors, rely on genomic scars that reflect the tumour's past, not its present. A test of current DNA-repair function would be better, but needs standardising.","summary":"Genomic scar assays (for example the Myriad myChoice score) predict PARP inhibitor benefit imperfectly and remain positive after resistance develops. Functional assays (RAD51 foci formation on tissue) measure current repair capacity and have shown promise in retrospective series. A consortium to standardise the RAD51 assay (antibodies, scoring, reference tissue) and validate it prospectively in a PARP inhibitor trial would give a dynamic, mechanism-based biomarker.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Biomarkers are not validated or standardised): Fernandez et al., Examination of low ERBB2 protein expression in breast cancer tissue (JAMA Oncology 2022)","url":"https://doi.org/10.1001/jamaoncol.2021.7239"}],"tags":[],"related":["hrd","parp-inhibitor","bh3-profiling"],"cancers":["ovarian"],"sections":[],"technologies":["hrd-testing"],"targets":["parp","brca"],"drugs":["olaparib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-biomarker-validation"],"keyPapers":["paper-fernandez-jama-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A standardised functional HRD assay will identify PARP inhibitor benefit in patients scored HRD-negative by genomic scars and will predict lack of benefit in scar-positive tumours that have restored repair, improving the hazard ratio for benefit in the assay-positive group by at least 20% over scar-based selection.","rationale":"Functional assays track the phenotype that the drug exploits; scars are a fossil record. Analogous functional testing (BH3 profiling) has predicted venetoclax response.","test":"Run the standardised assay on archived samples from a PARP inhibitor maintenance trial with prespecified analysis; if positive, embed prospectively in the next trial.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":4},{"id":"idea-fund-biomarker-validation-fund","kind":"idea","name":"A fund for prospective validation of academic biomarkers and companion diagnostics","aka":[],"tldr":"Thousands of tests that could predict who benefits from a treatment are published and never validated. A fund would pay for the boring but essential confirmation studies in independent patient groups.","summary":"A fund that pays for locked-down assay development, analytical validation and prospective or prospective-retrospective clinical validation of academic biomarkers with strong signals (predictive signatures, ctDNA thresholds, imaging or pathology AI scores), using banked samples from completed randomised trials under standard access agreements and independent statistical analysis. Diagnostics are far less profitable than drugs, so companies rarely take on validation of academic markers, and academic groups lack money for the multi-centre studies regulators and guidelines require. Prioritisation favours biomarkers that would spare patients ineffective treatment or de-escalate therapy.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The valley of death between lab and product): Butler, Translational research: crossing the valley of death (Nature 2008)","url":"https://doi.org/10.1038/453840a"}],"tags":[],"related":["idea-fund-trial-biospecimen-commons","idea-ai-her2-low-scoring"],"cancers":[],"sections":[],"technologies":["companion-diagnostic","mrd-testing","digital-pathology-ai"],"targets":[],"drugs":["oncotype-dx","signatera"],"companies":[],"institutions":[],"pathways":[],"terms":["companion-diagnostic-term","ppv"],"trials":[],"people":[],"bottlenecks":["b-translational-valley","b-biomarker-validation"],"keyPapers":["paper-butler-nature"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A biomarker validation fund of $30 million a year moves at least ten academic biomarkers per five years to guideline-endorsed or regulator-recognised status, compared with very few today, with at least three leading to treatment de-escalation or avoidance in practice.","rationale":"The tests that changed practice (Oncotype DX, MammaPrint, MSI, PD-L1 in specific contexts) all required prospective-retrospective validation on trial cohorts; the NCI's Biomarker, Imaging and Quality of Life Studies Funding Program and EORTC's SPECTA show the path exists but is small. Access to trial samples and independent analysis are the bottlenecks money can fix.","test":"Fund validation of five biomarkers on banked randomised-trial samples and compare time to guideline consideration and regulatory recognition with matched unfunded biomarkers.","maturity":"speculative","actor":"philanthropy","cost":"medium","horizonYears":4},{"id":"idea-moon-funded-second-opinion","kind":"idea","name":"A funded expert second opinion for every new high-stakes or rare cancer diagnosis","aka":[],"tldr":"Anyone diagnosed with a rare or complex cancer gets an automatic remote review by a specialist centre, paid for by the health system, before treatment starts.","summary":"Second opinions change diagnosis or management in a substantial minority of rare cancer cases (sarcoma, lymphoma subtyping, neuroendocrine tumours) and pathology discordance for rare tumours is well documented. Reference-centre networks (French NETSARC, EURACAN) show the model. The proposal is an entitlement to a remote expert review, delivered through virtual tumour boards, funded per case, with turnaround within 10 working days and the report returned to both the local team and the patient in plain language.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Patients lack understanding, navigation and agency): Basch et al., Overall survival results of a trial assessing patient-reported outcomes for symptom monitoring during routine cancer treatment (JAMA 2017)","url":"https://doi.org/10.1001/jama.2017.7156"}],"tags":[],"related":[],"cancers":["sarcoma","neuroendocrine","dlbcl"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-patient-voice","b-rare-cancers"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Systematic expert review changes management in over 20% of rare-cancer cases and improves guideline concordance and survival in sarcoma and lymphoma compared with unreviewed care.","rationale":"Expertise is concentrated; patients are not. Moving information is cheaper than moving patients, and review at diagnosis is when it changes the most.","test":"Regional pragmatic trial randomising rare-cancer diagnoses to automatic review versus opt-in; primary endpoint rate of major management change and 2-year outcomes.","maturity":"early-clinical","actor":"payer","cost":"medium","horizonYears":2},{"id":"idea-fund-organoid-translation-gate","kind":"idea","name":"A funded organoid and PDX panel as the go/no-go gate before IND-enabling money","aka":[],"tldr":"Before any academic compound gets money for pre-trial studies, it would have to show activity in a standard panel of patient-derived tumour models run by an independent centre, so weak candidates are stopped early.","summary":"A central facility maintains a standardised, molecularly characterised panel of patient-derived organoids and xenografts across cancer types (drawing on EurOPDX, the NCI Patient-Derived Models Repository and Human Cancer Models Initiative collections) and tests every candidate nominated for IND-enabling funding in a blinded, pre-registered protocol with clinically relevant exposure. Results are published regardless of outcome. Funding for toxicology and CMC is contingent on passing pre-agreed activity criteria. This replaces the variable, investigator-run efficacy evidence that currently supports translational decisions.","asOf":"2026-09-08","links":[{"label":"NCI Patient-Derived Models Repository","url":"https://pdmr.cancer.gov/"}],"tags":[],"related":["cancer-models","idea-fund-replication-set-aside","idea-fund-ind-enabling-fund","idea-organoid-guided-adc"],"cancers":[],"sections":[],"technologies":["organoids","pdx-models","functional-drug-testing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-translational-valley","b-preclinical-models"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Candidates that pass an independent, blinded PDX/organoid gate have a phase 2 objective response or progression-free survival signal at least twice as often as historical academic candidates that were advanced on investigator-generated data alone.","rationale":"Retrospective studies show PDX and organoid response tracks patient response for many drug classes; NCI's PDMR and EurOPDX exist but are not used as a formal gate. Independent, blinded testing addresses the reproducibility and selection biases that inflate academic efficacy claims.","test":"Gate one translational fund's candidates for three years, publishing pass and fail results, and compare downstream clinical signals with the fund's prior ungated cohort.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":3},{"id":"idea-fund-organ-preservation-programme","kind":"idea","name":"A funded programme of organ-preservation trials to avoid radical surgery","aka":[],"tldr":"For some cancers, drugs and radiotherapy can now cure without removing the organ, sparing patients a stoma, a lost voice or a removed bladder. A dedicated programme would run the trials to prove where this is safe.","summary":"A trials programme testing non-operative and organ-preserving strategies against standard radical surgery: watch-and-wait after total neoadjuvant therapy in rectal cancer, immunotherapy-only in mismatch-repair-deficient tumours (following the dostarlimab rectal cancer results), bladder preservation with chemoradiotherapy and immunotherapy, larynx preservation, breast surgery omission after exceptional response, and oesophageal active surveillance. These trials are hard to fund because they remove a procedure rather than add a drug, but their quality-of-life value is large. The programme would include patient-reported outcomes and survivorship endpoints as co-primary, and shared surveillance protocols.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Surgery and radiotherapy cure most, get least): Sullivan et al., Global cancer surgery (Lancet Oncology Commission 2015)","url":"https://doi.org/10.1016/S1470-2045(15)00223-5"}],"tags":[],"related":["idea-fund-surgical-trials-network","idea-fund-omission-deescalation-trials"],"cancers":["colorectal","urothelial","head-and-neck","esophageal"],"sections":[],"technologies":[],"targets":[],"drugs":["dostarlimab","pembrolizumab"],"companies":[],"institutions":[],"pathways":[],"terms":["msi","neoadjuvant-adjuvant"],"trials":["azur-1","nct05855200","nct06062420","nct06256588","nct06567782"],"people":["myriam-chalabi"],"bottlenecks":["b-surgery-radiation-innovation","b-toxicity-qol"],"keyPapers":["paper-cercek-dostarlimab-rectal-nejm-2022","paper-sullivan-lancet-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A dedicated programme completes at least five randomised or well-controlled organ-preservation trials within seven years, at least three of which establish non-inferior survival with substantially better patient-reported function, changing guidelines in those indications.","rationale":"The OPRA and dostarlimab rectal cancer studies, the bladder-preservation trimodality data and the larynx-preservation trials show the biology allows organ preservation in selected patients; the barrier is the trials, which no company will fund and which surgical culture has been slow to run.","test":"Launch three trials in the first two years with pre-registered non-inferiority margins and patient-reported co-primary endpoints; track accrual and publication.","maturity":"being-tested-at-scale","actor":"research","cost":"large","horizonYears":5},{"id":"idea-tr2-negative-results-journal","kind":"idea","name":"A funder-backed, indexed journal of negative and inconclusive cancer results","aka":[],"tldr":"Create a proper, indexed journal that publishes failed experiments and trials quickly, with fees paid by funders so that there is no barrier to reporting failure.","summary":"Previous attempts (the Journal of Negative Results in BioMedicine, which ceased in 2017) lacked funder backing and prestige. A journal owned by a consortium of major cancer funders, indexed in PubMed, with rapid methods-focused review, no publication charge, and citation in funders' progress reports would create a credible venue. Rigour of methods, not direction of result, is the acceptance criterion.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Failures are hidden): Anderson et al., Compliance with results reporting at ClinicalTrials.gov (NEJM 2015)","url":"https://doi.org/10.1056/NEJMsa1409364"}],"tags":[],"related":["pubmed-europepmc","cruk","idea-tr2-preclinical-negative-registry"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-negative-results"],"keyPapers":["paper-anderson-n-engl-j-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"The journal publishes at least 300 negative or inconclusive oncology papers per year by year three, and citation analysis shows that these papers are cited in subsequent grant applications and protocols.","rationale":"Publication bias is partly a venue problem: authors report that no journal wants a null. Funder ownership addresses the prestige and cost barriers together.","test":"Launch with commitments from three funders; monitor submissions, time to decision, and citations at three years.","maturity":"speculative","actor":"philanthropy","cost":"small","horizonYears":2},{"id":"idea-acc-pooled-procurement-radiotherapy","kind":"idea","name":"A Gavi-style pooled purchaser for radiotherapy equipment and service","aka":[],"tldr":"Countries buying radiotherapy machines one at a time pay high prices and get poor service. A single global buyer negotiating for dozens of machines a year could cut prices and demand long-term support.","summary":"Gavi and the Global Fund demonstrated that aggregated demand and multi-year volume guarantees lower prices, stabilise supply, and shape products. Radiotherapy has no equivalent: each ministry negotiates alone, with limited technical capacity, and often receives a machine without a bunker, staff, or service plan. A pooled purchaser (hosted, for instance, alongside the IAEA's Rays of Hope) would set standard specifications, bundle service and training, and publish prices.","asOf":"2026-09-08","links":[{"label":"IAEA Rays of Hope","url":"https://www.iaea.org/services/rays-of-hope"}],"tags":[],"related":[],"cancers":[],"sections":["radiation"],"technologies":[],"targets":[],"drugs":[],"companies":["varian","elekta"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-global-access","b-drug-pricing"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Pooled procurement will reduce the delivered cost per treatment unit, including ten years of service, by at least 30% against the median bilateral price and shorten install-to-first-patient time to under twelve months.","rationale":"Aggregation works when the product is standardisable and demand is predictable; radiotherapy capital needs in LMICs are both, and the global vendor base is small enough for volume commitments to matter.","test":"Commission a market-shaping analysis and a first pooled tender for ten machines across three countries with published unit prices and installed-to-operational timelines compared with recent bilateral purchases.","maturity":"speculative","actor":"policy","cost":"large","horizonYears":5},{"id":"idea-moon-federated-rwe-network","kind":"idea","name":"A global federated real-world evidence network at regulatory grade","aka":[],"tldr":"Connect hospital records across countries so that questions about how treatments work in real patients can be answered in weeks without moving the data, to a standard regulators accept.","summary":"Real-world evidence is fragmented, of variable quality and rarely accepted for decisions beyond safety. Federated analytics (OHDSI, DARWIN EU, Flatiron-style curated networks) demonstrate feasibility. The proposal is a global federated oncology network: common data model with oncology extensions, automated quality scoring, pre-registered analysis protocols executed locally with only aggregates shared, external control arm generation for rare indications, and a regulatory framework specifying when network evidence can support label expansions, pricing revisions and post-approval commitments.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Weak real-world evidence and registries): Gyawali, Hey & Kesselheim, Assessment of the clinical benefit of cancer drugs receiving accelerated approval (JAMA Intern Med 2019)","url":"https://doi.org/10.1001/jamainternmed.2019.0462"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["tempus","foundation-medicine"],"institutions":[],"pathways":[],"terms":["real-world-evidence"],"trials":[],"people":[],"bottlenecks":["b-real-world-evidence","b-data-silos"],"keyPapers":["paper-gyawali-jama-intern-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Network-generated evidence supports at least ten regulatory or reimbursement decisions in five years and reproduces trial results in emulation studies with high fidelity.","rationale":"Trial emulation has shown real-world data can reproduce randomised results when design is rigorous; federation solves privacy and sovereignty and scale simultaneously.","test":"Run twenty pre-registered trial emulations across the network and compare with the trials; then submit external control evidence for a rare indication.","maturity":"early-clinical","actor":"data","cost":"large","horizonYears":4},{"id":"idea-fund-global-academic-phase-one-network","kind":"idea","name":"A global first-in-human network for academic cancer trials with single ethics review","aka":[],"tldr":"Academic first-in-human cancer trials recruit slowly because each hospital repeats ethics and regulatory review. Twenty to thirty academic phase 1 units across Europe, North America and Asia would share protocol templates, one mutually recognised review, a joint safety committee and harmonised contracts, so a trial opens at every site within weeks and rare molecular subtypes can be pooled.","summary":"Twenty to thirty academic phase 1 oncology units across Europe, North America and Asia agree common protocols templates, a single mutually-recognised ethics and scientific review, a shared safety committee and harmonised contracts, so an academic first-in-human trial approved by the network opens at all sites within weeks. The EU Clinical Trials Regulation and US single-IRB rules already allow much of this; the missing part is an organisation that operates it for academic sponsors. The network also concentrates rare molecular subtypes and rare cancers, where single-site academic trials never accrue.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The valley of death between lab and product): Butler, Translational research: crossing the valley of death (Nature 2008)","url":"https://doi.org/10.1038/453840a"}],"tags":[],"related":["idea-fund-public-nonprofit-cro","idea-fund-translational-institutes-gmp"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["curie-nki-eortc"],"institutions":["royal-marsden","gustave-roussy","mskcc"],"pathways":[],"terms":["basket-umbrella-platform"],"trials":[],"people":[],"bottlenecks":["b-translational-valley","b-regulatory-fragmentation","b-trial-enrolment"],"keyPapers":["paper-butler-nature"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Academic first-in-human trials run through the network accrue at least three times faster than comparable single-institution academic trials and reach a recommended phase 2 dose within eighteen months in the majority of cases.","rationale":"Industry phase 1 trials open globally through CRO networks; academic ones do not, and rare-cancer academic trials routinely close for slow accrual. The EORTC and the Children's Oncology Group show that academic multinational early-phase trials work when infrastructure is shared.","test":"Run five academic first-in-human trials through a pilot network of ten units and compare activation time and accrual rate with matched single-centre trials.","maturity":"speculative","actor":"regulator","cost":"medium","horizonYears":4},{"id":"idea-fund-global-cancer-fund","kind":"idea","name":"A Global Fund for cancer care in low- and middle-income countries","aka":[],"tldr":"Copy the model that transformed HIV, TB and malaria care: a pooled international fund that pays for radiotherapy machines, pathology labs and essential cancer medicines where there are none.","summary":"A replenishment-based multilateral financing facility, governed with recipient countries, that funds radiotherapy capacity (building on IAEA Rays of Hope), pathology and diagnostic networks, pooled procurement of essential oncology medicines at negotiated prices, and workforce training. Allocation would follow burden and readiness formulas. Cancer now kills more people in LMICs than HIV, TB and malaria combined, but has no comparable financing vehicle; philanthropic and bilateral efforts are fragmented.","asOf":"2026-09-08","links":[{"label":"IAEA Rays of Hope","url":"https://www.iaea.org/services/rays-of-hope"},{"label":"The Global Fund","url":"https://www.theglobalfund.org/"}],"tags":[],"related":["idea-fund-lmic-burden-match","idea-fund-lmic-radiotherapy-finance"],"cancers":["cervical","breast-hr-positive","hcc"],"sections":[],"technologies":["imrt-igrt","brachytherapy"],"targets":[],"drugs":[],"companies":[],"institutions":["iarc","tata-memorial"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-funding-allocation","b-global-access"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A pooled fund disbursing over a billion dollars a year raises radiotherapy capacity in recipient countries by at least 50% and essential-medicine availability above 80% within five years, with measurable improvement in stage-adjusted survival for cervical and breast cancer within ten.","rationale":"The Global Fund and Gavi show that pooled procurement, predictable financing and country-led allocation can deliver complex health interventions at scale; radiotherapy and generic chemotherapy are cost-effective by any standard, and price falls of 90% for HIV drugs followed pooled purchasing.","test":"A five-country pilot with a fund of a few hundred million dollars, pre-registered indicators for capacity, availability and stage-adjusted survival, compared with matched non-participating countries.","maturity":"speculative","actor":"policy","cost":"large","horizonYears":5},{"id":"idea-moon-negative-results-ledger","kind":"idea","name":"A global ledger of negative results and failed compounds with mandatory deposition","aka":[],"tldr":"Every failed cancer drug, experiment and trial gets recorded in one open ledger, so nobody repeats a failure that has already cost years and millions.","summary":"Most preclinical negatives are never published, most discontinued compounds vanish with their data, and terminated trials often report nothing. The proposal is a ledger with structured entries (target, compound, model, endpoint, result, reason for stopping) required as a condition of public funding, journal publication and regulatory submission, with a safe harbour for industry deposition of discontinued asset data, and incentives (citations, credit) for negative-result deposition. Discontinued compounds with clean safety could be listed for repurposing.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Failures are hidden): Anderson et al., Compliance with results reporting at ClinicalTrials.gov (NEJM 2015)","url":"https://doi.org/10.1056/NEJMsa1409364"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-negative-results","b-reproducibility","b-ip-collaboration"],"keyPapers":["paper-anderson-n-engl-j-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Within five years the ledger holds tens of thousands of negatives and measurably reduces duplicated preclinical programmes and trials of already-failed hypotheses, and yields repurposing candidates.","rationale":"Failure is the most common outcome and the least shared; a structured, required ledger corrects the publication bias that inflates hypotheses.","test":"Pilot with two funders and one company: measure deposition compliance, downstream citations and surveys of investigators who changed plans after consulting the ledger.","maturity":"speculative","actor":"policy","cost":"medium","horizonYears":3},{"id":"idea-reg-isotope-supply-observatory","kind":"idea","name":"A global medical isotope supply observatory with forecasts and shortage alerts","aka":[],"tldr":"Nobody publishes how much cancer isotope is made, where, or when supply will fall short. A public observatory would let hospitals and investors plan.","summary":"Supply and demand for lutetium-177, actinium-225, iodine-131 and their precursors are opaque; producers guard volumes, and shortages surface only when clinics cancel doses. The proposal is an observatory, hosted by the IAEA or OECD NEA with WHO, that collects confidential production and capacity data from producers under aggregation rules, publishes quarterly supply-demand balances and five-year forecasts, and issues shortage alerts to clinics and regulators. It would also track trial-stage demand so producers can invest ahead of approvals.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Manufacturing cost and time for living and radioactive medicines): Hernandez, Prasad & Gellad, Total costs of chimeric antigen receptor T-cell immunotherapy (JAMA Oncology 2018)","url":"https://doi.org/10.1001/jamaoncol.2018.0977"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["radioligand-therapy","targeted-alpha-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-manufacturing-cell-therapy","b-data-silos"],"keyPapers":["paper-hernandez-jama-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Publication of forecasts is followed by earlier capacity investment decisions (measured by announced projects relative to forecast shortfalls) and a fall in unanticipated clinic-level shortages within three years.","rationale":"Transparent supply data (as in energy and food markets) reduce boom-bust investment and allow health systems to plan; the molybdenum-99 experience showed that opaque supply led to repeated crises.","test":"Establish the observatory for lutetium-177 first, publish two years of quarterly balances, and evaluate accuracy of forecasts and changes in shortage reports.","maturity":"speculative","actor":"data","cost":"small","horizonYears":2},{"id":"idea-moon-global-open-trials-os","kind":"idea","name":"A global open trials operating system any hospital can plug into","aka":[],"tldr":"Build the shared software, legal templates and data standards that let any hospital in the world join a cancer trial in weeks instead of years, the way the internet let any computer join the network.","summary":"Trial start-up takes many months per site because every sponsor, country and hospital reinvents contracts, ethics submissions, data capture and monitoring. The proposal is an open-source, openly governed trials operating system: standard master agreements, a single global ethics dossier format accepted by participating regulators, e-consent and eligibility modules, mCODE-based data capture from electronic records, risk-based remote monitoring and open protocol templates, with certification of sites and a fund to connect hospitals in low- and middle-income countries.","asOf":"2026-09-08","links":[{"label":"Clinical Trials Transformation Initiative","url":"https://ctti-clinicaltrials.org/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["ai-trial-matching"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-enrolment","b-regulatory-fragmentation","b-trial-diversity"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Sites on the operating system open trials in under 60 days at a fifth of current start-up cost, and the share of global trial enrolment from middle-income countries doubles within five years.","rationale":"Open standards and shared infrastructure transformed payments, logistics and the web; trials remain artisanal. Regulatory convergence (ICH, reliance pathways) makes a shared dossier plausible now.","test":"Deploy across 100 hospitals in ten countries with five sponsors; compare start-up time, cost per patient and enrolment diversity against matched conventional sites.","maturity":"speculative","actor":"engineering","cost":"large","horizonYears":5},{"id":"idea-bio2-rapid-autopsy-commons","kind":"idea","name":"A global rapid tissue donation network for metastatic disease","aka":[],"tldr":"Almost all cancer deaths are caused by spread, yet metastatic tissue is rarely studied because rapid autopsy programmes exist at only a handful of centres. A funded 20-site network with one protocol, one consent framework and open sample access would collect donated tissue within hours of death.","summary":"Rapid autopsy programmes at a handful of centres have produced disproportionate insight into metastatic evolution and treatment resistance, but they are small, precariously funded and not interoperable. A funded 20-site network with a shared protocol, single consent framework, common data commons and open sample access would industrialise the most information-dense sample type in oncology.","asOf":"2026-09-08","links":[{"label":"Cancer Grand Challenges","url":"https://cancergrandchallenges.org"}],"tags":[],"related":["tcga-gdc","cbioportal","genie"],"cancers":[],"sections":[],"technologies":["single-cell-spatial","wes-wgs","proteomics"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["charles-swanton"],"bottlenecks":["b-metastasis-biology","b-preclinical-models","b-data-silos"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A shared-protocol network producing 500 multi-site metastatic donations per year yields at least ten validated metastasis-specific dependencies within five years that are absent from primary-tumour datasets.","rationale":"Large-scale primary tumour atlases transformed cancer biology because scale plus openness beat individual excellence. Metastasis has never had an equivalent: existing metastatic sequencing is mostly single-site biopsy material and lacks the paired multi-organ sampling that organotropism and resistance questions require.","test":"Fund a three-site pilot to demonstrate short warm-ischaemia protocols, harmonised consent and open data release; measure donations per year, organs per donor and external data requests served.","maturity":"early-clinical","actor":"philanthropy","cost":"large","horizonYears":5},{"id":"idea-bio1-undruggable-market-commitment","kind":"idea","name":"A guaranteed purchase prize for the first drug against a named hard target","aka":[],"tldr":"Governments promised in advance to buy vaccines that did not yet exist, and they got made. The same promise could be made for a drug against a target everyone has given up on.","summary":"Advance market commitments worked for pneumococcal vaccines and shaped COVID-19 vaccine supply. Applied to undruggable oncology targets, a public or philanthropic funder would commit to purchase a defined volume at a defined price for the first agent meeting a pre-specified efficacy bar against a designated target such as KRAS G12D in pancreatic cancer or gain-of-function mutant p53, with access conditions attached.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The undruggable drivers): Dang et al., Drugging the 'undruggable' cancer targets (Nature Reviews Cancer 2017)","url":"https://doi.org/10.1038/nrc.2017.36"}],"tags":[],"related":[],"cancers":["pancreatic"],"sections":[],"technologies":[],"targets":["kras","tp53"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-undruggable-targets","b-incentive-misalignment","b-funding-allocation"],"keyPapers":["paper-dang-nat-rev-cancer"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A committed purchase guarantee of sufficient size measurably increases the number of active industrial programmes against the designated target within three years of announcement.","rationale":"Investment in high-risk targets is limited by uncertain revenue rather than by scientific interest; demand-side instruments change that calculation without picking a technical approach.","test":"Announce one pilot commitment with a clear technical specification and independent adjudication, and count programme starts, patent filings and consortium formation against matched control targets over three years.","maturity":"speculative","actor":"policy","cost":"large","horizonYears":8},{"id":"idea-reg-guideline-fast-track-repurposed","kind":"idea","name":"A guideline fast track for repurposed drugs with phase 3 evidence but no manufacturer","aka":[],"tldr":"Guidelines usually wait for a drug to be licensed for a use before recommending it. For old drugs no one will license, guidelines should act directly on trial evidence.","summary":"Guideline bodies (NCCN, ESMO, NICE) do recommend off-label uses but often slowly and inconsistently for interventions without a sponsor to submit evidence. The proposal is a standing fast-track procedure in major guideline organisations, triggered automatically by publication of a registration-quality randomised trial of an off-patent drug, with a decision within six months, an explicit statement of the recommendation's reimbursement implications, and a mechanism for payers to adopt it in the absence of a label.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (No incentive to repurpose cheap drugs): Pantziarka et al., The Repurposing Drugs in Oncology (ReDO) Project (ecancer 2014)","url":"https://doi.org/10.3332/ecancer.2014.442"}],"tags":[],"related":["nccn","esmo-guidelines"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["esmo","asco"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-generic-repurposing","b-knowledge-diffusion"],"keyPapers":["paper-pantziarka-ecancermedicalscience"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Fast-tracked repurposed interventions reach guideline recommendation within six months of publication (versus a historical median of two or more years) and prescribing uptake within two years exceeds 50% of eligible patients.","rationale":"For off-patent drugs, guidelines rather than labels are the practical gateway to routine use and reimbursement; making the pathway explicit removes an arbitrary disadvantage relative to sponsored drugs.","test":"Audit the time from publication to guideline inclusion for the last ten positive repurposing trials; implement the fast track in one guideline body and measure the next five.","maturity":"speculative","actor":"clinic","cost":"small","horizonYears":2},{"id":"idea-fund-health-impact-fund-oncology","kind":"idea","name":"A Health Impact Fund pilot that pays for measured health gain instead of price","aka":[],"tldr":"Companies could choose to sell a new cancer drug at cost worldwide and instead be paid from a pooled fund according to how much health it actually delivers.","summary":"The Health Impact Fund proposal: an optional, government-financed pool that pays registered products annually for ten years in proportion to their measured health impact (quality-adjusted life years gained across all countries), on condition that the product is sold at the cost of manufacture everywhere. For oncology this rewards drugs that deliver large gains to many patients, including in low-income countries, rather than drugs that extract high prices from few. An oncology-only pilot with a few billion dollars and two or three products would test measurement feasibility and industry appetite.","asOf":"2026-09-08","links":[{"label":"Health Impact Fund","url":"https://healthimpactfund.org/"}],"tags":[],"related":["idea-fund-conditional-transferable-voucher","idea-fund-global-access-licensing-royalties"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-incentive-misalignment","b-global-access","b-drug-pricing"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"In a pilot, at least two oncology products register, health impact can be measured with acceptable uncertainty using registry and sales data, and registered products reach patients in low- and middle-income countries at volumes an order of magnitude above comparable priced products.","rationale":"The proposal has been developed in detail by economists and philosophers over fifteen years and is endorsed by several Nobel laureates; the pieces (impact measurement, cost-of-goods auditing, tiered access) exist separately. Oncology has strong outcome data and stark access inequalities, making it a fair test.","test":"A government-philanthropy consortium funds a five-year pilot with a small number of products and pre-registered impact measurement methodology; success is completed measurement, access volumes and industry willingness to register further products.","maturity":"speculative","actor":"policy","cost":"large","horizonYears":6},{"id":"idea-moon-literacy-first-design-standard","kind":"idea","name":"A health-literacy certification standard for oncology portals, letters and apps","aka":[],"tldr":"Cancer information tools must meet a tested standard: reading age around 12, main languages of the population, audio versions and clear numbers, or they are not certified for use.","summary":"Patient letters, portals and apps are written for the people who build them. A certification (like accessibility standards WCAG) for health literacy would specify reading level, numeracy formats (natural frequencies, icon arrays), translation coverage matched to the served population, and testing with low-literacy users. Health systems and regulators would require certification for patient-facing oncology tools.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Patients lack understanding, navigation and agency): Basch et al., Overall survival results of a trial assessing patient-reported outcomes for symptom monitoring during routine cancer treatment (JAMA 2017)","url":"https://doi.org/10.1001/jama.2017.7156"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-patient-voice","b-trial-diversity"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Certified tools raise comprehension and portal use among patients with lower education and non-dominant languages and narrow the gap in trial awareness and adherence.","rationale":"Accessibility standards changed the web because they were checkable and required; health literacy standards exist in guidance but are not enforced.","test":"Certify a portal and letter set in one system; compare comprehension and engagement across education strata before and after, and against a control system.","maturity":"speculative","actor":"engineering","cost":"small","horizonYears":2},{"id":"idea-bio1-negative-preclinical-repository","kind":"idea","name":"A home for the animal and organoid experiments that failed","aka":[],"tldr":"Failed laboratory experiments are rarely published, so other teams repeat them. A searchable place to deposit them would save years of duplicated work.","summary":"A structured repository for negative or null preclinical results, with a minimal reporting template (model, agent, dose, endpoint, effect size, confidence interval), digital object identifiers so deposits are citable, and funder credit for deposition. Existing journals for negative results have failed because they carry no career value; funder mandates and citable deposits change that calculus.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Lab models that fail to predict what happens in patients): Wong, Siah & Lo, Estimation of clinical trial success rates (Biostatistics 2019)","url":"https://doi.org/10.1093/biostatistics/kxx069"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["cruk","nci"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-preclinical-models","b-negative-results","b-reproducibility"],"keyPapers":["paper-wong-biostatistics"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A funder-mandated repository accumulates enough deposits in three years that documented duplicate-effort avoidance and meta-analytic corrections to published effect sizes can be demonstrated.","rationale":"Meta-research consistently shows that a large fraction of preclinical oncology findings do not replicate; the missing data are not lost, they are unpublished and sitting on hard drives.","test":"One large funder requires deposition as a condition of final report sign-off for three years; measure deposit rate, reuse, and effect-size shifts in updated meta-analyses.","maturity":"speculative","actor":"philanthropy","cost":"small","horizonYears":3},{"id":"idea-reg-middle-income-negotiation-bloc","kind":"idea","name":"A joint price negotiation bloc for middle-income countries, modelled on Beneluxa","aka":[],"tldr":"Small European countries have started negotiating cancer drug prices together. A bloc of large middle-income countries would have far more bargaining power.","summary":"Beneluxa, the Nordic Pharmaceutical Forum and the Valletta Declaration group pool HTA and negotiation among European countries with modest results but proof of feasibility. Middle-income countries (Brazil, Mexico, Colombia, South Africa, Indonesia, Thailand, Egypt and others) negotiate alone and often pay list prices comparable to high-income countries for oncology drugs. The proposal is a formal negotiation bloc with a shared HTA secretariat, common evidence dossiers, and joint tenders or price agreements for new oncology medicines, backed by the PAHO Strategic Fund model for procurement.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Prices and value): Prasad, De Jesús & Mailankody, The high price of anticancer drugs: origins, implications, barriers, solutions (Nat Rev Clin Oncol 2017)","url":"https://doi.org/10.1038/nrclinonc.2017.31"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-drug-pricing","b-global-access"],"keyPapers":["paper-prasad-nat-rev-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Bloc members achieve net prices for new oncology medicines at least 30% below what they paid individually for comparable launches, and time from approval to public availability falls.","rationale":"Bargaining power scales with volume and with credible willingness to walk away; a bloc of several hundred million people can offer both, and a shared HTA cuts each member's assessment costs.","test":"Convene five middle-income countries to run three joint negotiations for new oncology medicines over two years and compare achieved prices with prior individual agreements for similar products.","maturity":"speculative","actor":"policy","cost":"small","horizonYears":3},{"id":"idea-fund-compulsory-combination-access","kind":"idea","name":"A legal right to obtain marketed cancer drugs at cost for combination trials","aka":[],"tldr":"If a company refuses to supply its approved drug for a well-designed independent trial combining it with a rival's drug, the law would let the trial buy it at manufacturing cost, with results shared back.","summary":"A research-access provision, analogous to compulsory licensing but for trial supply: an independent scientific committee can certify an academic or non-profit combination trial as in the public interest, after which the patent holder must supply the drug at a regulated cost-of-goods price or license a generic maker to do so, in exchange for full access to the trial's data and a right to use results in labelling. The provision only bites when voluntary agreement fails and so mostly changes bargaining positions. It addresses the documented pattern of companies declining to supply comparators or partners for trials that might disadvantage their product.","asOf":"2026-09-08","links":[{"label":"FDA guidance on codevelopment of two or more investigational drugs","url":"https://www.fda.gov/regulatory-information/search-fda-guidance-documents/codevelopment-two-or-more-new-investigational-drugs-use-combination"}],"tags":[],"related":["idea-fund-combination-patent-pool","idea-fund-antitrust-safe-harbour","idea-fund-head-to-head-mandate"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-ip-collaboration","b-combination-space"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Introducing a certified research-access right increases the number of cross-company combination and head-to-head academic trials started per year by at least half in the jurisdiction, with the right actually invoked in fewer than one in five cases because voluntary supply improves.","rationale":"Research exemptions in patent law exist in most jurisdictions but do not cover supply; the mere existence of compulsory licensing has repeatedly lowered prices in negotiations without being used. Trials such as STAMPEDE and the RT-IO platforms have been delayed or reshaped by supply refusals.","test":"Enact in one jurisdiction with a five-year sunset and track combination and comparative trial starts, supply refusals reported to the committee, and invocations.","maturity":"speculative","actor":"policy","cost":"small","horizonYears":3},{"id":"idea-acc-28-day-diagnosis-standard","kind":"idea","name":"A legislated, publicly reported 28-day standard from urgent referral to diagnosis","aka":[],"tldr":"Set a legal limit: anyone referred with suspected cancer should be told within 28 days whether they have it. Publish how every hospital performs each month.","summary":"England's Faster Diagnosis Standard requires that 75% of patients referred urgently are told they have cancer or do not within 28 days, with monthly public reporting by trust. Whatever the debate on the threshold, the combination of a defined interval, a named responsible organisation, and public data has focused management attention on diagnostic pathways. Most countries have no equivalent. The proposal is to adopt and adapt it, with the threshold set by local capacity and tightened over time.","asOf":"2026-09-08","links":[{"label":"NHS England Faster Diagnosis Standard (archived copy)","url":"https://web.archive.org/web/20251231165538/https://www.england.nhs.uk/cancer/faster-diagnosis/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-care-fragmentation","b-early-detection"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Health systems introducing a published diagnosis-interval standard will reduce the 90th-percentile referral-to-diagnosis interval by at least 30% within three years.","rationale":"Public reporting of waiting times has repeatedly changed hospital behaviour where the measure is simple and attributable; the diagnostic interval is both.","test":"Compare interval distributions before and after introduction in an adopting jurisdiction, and against a neighbouring system without the standard.","maturity":"being-tested-at-scale","actor":"policy","cost":"medium","horizonYears":3},{"id":"idea-data-ai-liability-safe-harbour","kind":"idea","name":"A liability framework for clinical AI: safe harbour for clinicians, liability for makers","aka":[],"tldr":"Make clear who is responsible when an AI tool contributes to a mistake: protect doctors who use approved tools as intended, and hold makers responsible for the tool's performance.","summary":"Liability uncertainty holds hospitals and clinicians back from adopting AI: the clinician may bear responsibility for a tool they cannot inspect. The proposal is legislation or regulatory guidance establishing a safe harbour for clinicians who follow a registered, validated model within its labelled use, coupled with product-liability accountability for developers for performance within the labelled use, and a no-fault compensation scheme for patients harmed by AI errors, as exists for vaccines in several countries.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (AI that is built but not validated or deployed): Wu et al., How medical AI devices are evaluated: limitations and recommendations from an analysis of FDA approvals (Nature Medicine 2021)","url":"https://doi.org/10.1038/s41591-021-01312-x"}],"tags":[],"related":["idea-data-clinical-ai-model-registry"],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-ai-validation"],"keyPapers":["paper-wu-nat-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A clear liability framework will increase adoption of validated AI tools by clinicians and reduce defensive overriding, without an increase in patient harm, in jurisdictions that adopt it versus those that do not.","rationale":"Liability shields (Good Samaritan laws, vaccine injury compensation) have changed professional behaviour where uncertainty deterred beneficial action; surveys of clinicians rank liability among the top barriers to AI use.","test":"Compare AI adoption and override rates in a jurisdiction that adopts the framework with matched jurisdictions over three years; track claims and compensation cases.","maturity":"speculative","actor":"policy","cost":"small","horizonYears":3},{"id":"idea-moon-adult-late-effects-registry","kind":"idea","name":"A lifelong late-effects registry linked to every treatment for adult survivors","aka":[],"tldr":"Children treated for cancer are followed for decades in a study that has changed how they are treated. Adults have nothing similar. Build it.","summary":"The Childhood Cancer Survivor Study transformed paediatric protocols by quantifying late cardiac, second-cancer and endocrine effects. Adult survivors, now over 18 million in the US alone, lack systematic long-term follow-up linked to treatment exposures, so late effects of immunotherapy, antibody-drug conjugates and modern radiotherapy are unknown. The proposal is a national registry linking treatment records, PROs and administrative outcomes for all adult survivors with consent, with open access for research.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Toxicity and quality of life are undervalued): Di Maio et al., Symptomatic toxicities experienced during anticancer treatment: agreement between patient and physician reporting (JCO 2015)","url":"https://doi.org/10.1200/JCO.2014.57.9334"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["karolinska","nci"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol","b-survivorship"],"keyPapers":["paper-di-maio-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Within ten years the registry quantifies late effects for at least twenty modern regimens and leads to at least three changes in guideline dosing or surveillance.","rationale":"Late effects are invisible in trials that end at five years; only linked long-term data reveal them, and the paediatric precedent shows the payoff.","test":"Build in one country with existing registries (Nordic model) and demonstrate linkage completeness and first late-effect estimates within three years.","maturity":"early-clinical","actor":"data","cost":"medium","horizonYears":5},{"id":"idea-tr1-live-trial-slot-api","kind":"idea","name":"A live 'seats available' feed for trial slots, like airline inventory","aka":[],"tldr":"Trial registries say a study is 'recruiting' long after it stopped, and never say whether a slot is actually open this week. A live feed of open slots per arm and site would let clinicians refer with confidence.","summary":"Sponsors and sites publish, via a standard API, per-arm and per-site slot availability updated at least weekly (open, waitlist, closed, expected reopening), consumed by matching tools, genomic report generators and the public registry. Incentive: registries flag trials whose status has not been confirmed within 30 days as 'status unverified'.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Trials enrol too few, too slowly): Unger et al., Systematic review of barriers to cancer trial participation (JNCI 2019)","url":"https://doi.org/10.1093/jnci/djy221"}],"tags":[],"related":["clinicaltrials-gov"],"cancers":[],"sections":[],"technologies":["ai-trial-matching"],"targets":[],"drugs":[],"companies":["cancer-commons"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-enrolment","b-data-silos"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Referrals made against live slot data will convert to enrolment at a higher rate and fewer patients will be referred to closed arms, measured by referral-outcome tracking at participating centres.","rationale":"Stale status is a leading cause of failed referrals and of clinician distrust of matching tools. Inventory visibility solved analogous problems in travel and retail.","test":"Pilot with three sponsors and one regional referral network; compare referral-to-enrolment conversion and wasted referrals against the prior year.","maturity":"speculative","actor":"engineering","cost":"medium","horizonYears":2},{"id":"idea-prev-live-stage-dashboard","kind":"idea","name":"A live national dashboard of stage at diagnosis as the scorecard for early detection","aka":[],"tldr":"You cannot manage what you do not measure quickly. Publishing stage at diagnosis by cancer and region every quarter, not years later, would show whether detection efforts are working.","summary":"Registry stage data typically lag two to three years. Propose near-real-time staging capture from pathology and multidisciplinary-team systems feeding a public dashboard, with region-level early-stage proportions and route to diagnosis, so screening and symptom-pathway interventions can be evaluated within a year. England's Rapid Cancer Registration Dataset shows feasibility.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The hardest cancers are found late): Crosby et al., Early detection of cancer (Science 2022)","url":"https://doi.org/10.1126/science.aay9040"}],"tags":[],"related":["seer"],"cancers":[],"sections":["early-detection"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["stage-shift","tnm-staging"],"trials":[],"people":[],"bottlenecks":["b-early-detection","b-data-silos"],"keyPapers":["paper-crosby-science"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Quarterly stage reporting with under six months' lag is achievable for at least 90% of cases and shortens the evaluation cycle of detection interventions from five years to under two.","rationale":"Fast feedback is what let COVID dashboards drive policy; cancer detection has no equivalent.","test":"Build in one national registry; compare completeness and lag against gold-standard registration.","maturity":"early-clinical","actor":"data","cost":"small","horizonYears":2},{"id":"idea-acc-chemo-stockout-early-warning","kind":"idea","name":"A live stock-out map for essential chemotherapy drugs","aka":[],"tldr":"Hospitals in poorer countries often run out of basic, cheap chemotherapy for weeks. A shared live map of stock levels would let buyers and donors act before a child's treatment is interrupted.","summary":"Stock-outs of cisplatin, methotrexate, asparaginase, vincristine, and other generic cytotoxics are common in public hospitals across Africa and parts of Asia, and are a leading cause of treatment abandonment and cure-rate loss in curable cancers. Consumption data exists in hospital pharmacies but is not shared. A lightweight reporting system (SMS or app) feeding a regional dashboard, with a buffer-stock fund and a pre-negotiated emergency supplier, would turn reactive shortages into managed ones.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Most of the world has almost no cancer care): WHO fact sheet, Cancer","url":"https://www.who.int/news-room/fact-sheets/detail/cancer"}],"tags":[],"related":[],"cancers":["all-leukemia","hodgkin-lymphoma"],"sections":["chemotherapy"],"technologies":["cytotoxic-chemotherapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-global-access","b-data-silos"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Districts reporting into a stock-out early-warning system with an emergency buffer will reduce chemotherapy stock-out days per year by at least 60% and reduce documented treatment interruptions.","rationale":"Malaria and HIV programmes cut stock-outs sharply with the same tools (logistics management information systems and buffer stocks). Oncology has never had a programme-level supply chain.","test":"Twelve-month pilot in one country with monthly stock-out days, interruption episodes in paediatric ALL and Hodgkin protocols, and cost per averted interruption as endpoints.","maturity":"speculative","actor":"data","cost":"small","horizonYears":2},{"id":"idea-tr2-failure-taxonomy","kind":"idea","name":"A machine-readable taxonomy of why cancer drugs fail","aka":[],"tldr":"Drugs fail for distinct reasons: wrong target, drug never reached it, unacceptable toxicity, unselected population or poor trial design. A shared machine-readable taxonomy applied to every discontinued oncology programme in public pipeline databases would show where the system breaks, as AstraZeneca and Pfizer's own attrition analyses did.","summary":"Analyses of attrition (for example those published by AstraZeneca and Pfizer on their own pipelines) show that failure reasons are learnable but rarely recorded consistently. A shared taxonomy (target biology, exposure, safety, efficacy in unselected population, biomarker failure, design, commercial) applied to every discontinued oncology programme in public pipeline databases would enable system-level diagnosis and comparison across sponsors and decades.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Failures are hidden): Anderson et al., Compliance with results reporting at ClinicalTrials.gov (NEJM 2015)","url":"https://doi.org/10.1056/NEJMsa1409364"}],"tags":[],"related":["idea-tr2-termination-reports","idea-tr2-target-failure-index"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-negative-results","b-translational-valley"],"keyPapers":["paper-anderson-n-engl-j-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Applying the taxonomy to a decade of discontinuations will show that at least a third of efficacy failures were preceded by inadequate target-validation or exposure evidence, quantifying an avoidable loss.","rationale":"Aviation and surgery improved by classifying failure. Pharma's 'five Rs' framework (right target, tissue, safety, patient, commercial) is a start that has not been applied openly.","test":"Curate 500 discontinued oncology programmes with two independent coders; publish inter-rater reliability and the distribution of causes.","maturity":"speculative","actor":"data","cost":"small","horizonYears":2},{"id":"idea-acc-portable-treatment-summary","kind":"idea","name":"A machine-readable treatment summary handed to every patient and readable by any hospital","aka":[],"tldr":"Patients moving between hospitals often carry paper folders or nothing. A standard electronic summary of diagnosis, treatments, and doses that any system can read would stop repeated tests and dangerous gaps.","summary":"Cancer care crosses institutions, regions, and countries, and treatment history is frequently lost or reconstructed from memory. A standard summary (diagnosis, stage, molecular results, regimens with cumulative doses, radiotherapy fields and doses, key toxicities, follow-up plan) in an interoperable format such as HL7 FHIR mCODE, generated automatically and held by the patient, would make continuity possible. The technical standards exist; the missing pieces are mandates and defaults.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Fragmented care and guideline gaps): Hanna et al., Mortality due to cancer treatment delay: systematic review and meta-analysis (BMJ 2020)","url":"https://doi.org/10.1136/bmj.m4087"}],"tags":[],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-care-fragmentation","b-data-silos","b-survivorship"],"keyPapers":["paper-hanna-bmj"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Regions requiring a standard summary at each transition will reduce duplicated imaging and pathology by at least 20% and reduce cumulative-dose errors (for instance, anthracycline over-exposure) to near zero.","rationale":"Discharge summaries and immunisation records show that standardised, patient-held documents reduce errors and duplication when they are the default output of the system rather than an extra task.","test":"Implementation in two health systems with measurement of duplicate tests, dose errors, and time to reconstruct history in receiving hospitals.","maturity":"early-clinical","actor":"data","cost":"medium","horizonYears":3},{"id":"idea-prev-mced-pretest-decision-aid","kind":"idea","name":"A mandatory decision aid before any multi-cancer blood test","aka":[],"tldr":"People are told a blood test can find fifty cancers, but not how many false alarms or how much is unknown. A short, tested decision aid before the test would make consent real.","summary":"People are told a blood test can find fifty cancers but not how many false alarms or how much is unknown, so this idea requires a standardised, regulator-approved decision aid before any multi-cancer blood test. The aid would quantify false positives, unresolved positives, overdiagnosis uncertainty and the absence of outcome evidence, since consumer marketing of MCEDs has run ahead of trials. Decision aids improve knowledge and reduce overuse in PSA screening, and MCEDs carry greater uncertainty. A 2,000-person RCT in a screening-age population would measure informed choice and uptake. Speculative in maturity, it addresses the bottlenecks Overdiagnosis and false alarms, Patients lack understanding, navigation and agency, and Misinformation and unproven therapies.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Overdiagnosis and false alarms): Welch & Black, Overdiagnosis in cancer (JNCI 2010)","url":"https://doi.org/10.1093/jnci/djq099"}],"tags":[],"related":[],"cancers":[],"sections":["early-detection"],"technologies":["mced"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-overdiagnosis","b-patient-voice","b-misinformation"],"keyPapers":["paper-welch-j-natl-cancer-inst"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"The decision aid improves knowledge scores by at least 20 points and reduces uptake among low-risk individuals without reducing uptake among high-risk individuals.","rationale":"Decision aids improve knowledge and reduce overuse in PSA screening; MCEDs carry greater uncertainty.","test":"Run a 2,000-person RCT in a screening-age population.","maturity":"speculative","actor":"regulator","cost":"small","horizonYears":2},{"id":"idea-tr1-mandatory-older-adult-cohort","kind":"idea","name":"A mandatory over-70s cohort with geriatric assessment in every pivotal trial","aka":[],"tldr":"Most people with cancer are over 65, but trials mostly enrol younger, fitter people. Requiring a group of older patients, assessed for frailty, in every big trial would show whether the drug works and is safe for those most likely to receive it.","summary":"Registrational trials include a pre-specified cohort or stratum of patients aged 70 and over, enrolled in proportion to disease incidence, with baseline geriatric assessment (function, cognition, comorbidity, falls, nutrition) recorded, and with efficacy, toxicity and dose modification reported by frailty category. FDA's Project Silver and the older-adults guidance support inclusion; the proposal makes it a quantitative requirement.","asOf":"2026-09-08","links":[{"label":"FDA: Inclusion of Older Adults in Cancer Clinical Trials","url":"https://www.fda.gov/regulatory-information/search-fda-guidance-documents/inclusion-older-adults-cancer-clinical-trials"},{"label":"FDA Oncology Center of Excellence: Project Silver (archived copy)","url":"https://web.archive.org/web/20250120094403/https://www.fda.gov/about-fda/oncology-center-excellence/project-silver"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["geriatric-assessment"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-diversity","b-aging-comorbidity","b-dose-optimisation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Trials with an older-adult cohort will find clinically relevant differences in toxicity or dosing in a meaningful fraction of agents, leading to label guidance for frail patients at approval rather than years later.","rationale":"Older patients have different pharmacokinetics, more comorbidity and different goals; post-approval real-world toxicity is often higher than trial data predicted. Geriatric-assessment-guided care reduced toxicity in randomised trials.","test":"Compare the frequency of age- or frailty-specific label statements at approval for drugs with and without a mandated cohort, and real-world discontinuation rates in older patients.","maturity":"early-clinical","actor":"regulator","cost":"medium","horizonYears":3},{"id":"idea-moon-patient-experience-label","kind":"idea","name":"A mandatory patient-experience section in every cancer drug label and approval","aka":[],"tldr":"The official information about a new cancer drug must include what patients on the trial actually reported about side-effects and daily life, not only survival curves.","summary":"The FDA Oncology Center of Excellence's Project Patient Voice began publishing patient-reported symptom data from trials, but labels remain silent on patient-reported outcomes for most drugs. The proposal is a required, standardised patient-experience section (PRO-CTCAE symptom frequency, physical function trajectory, time toxicity) in every oncology label and public assessment report, and a voting patient member on advisory committees with access to the same data.","asOf":"2026-09-08","links":[{"label":"FDA Project Patient Voice","url":"https://www.fda.gov/about-fda/oncology-center-excellence/project-patient-voice"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-patient-voice","b-regulatory-fragmentation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Labels with patient-experience sections change prescribing towards better-tolerated regimens when efficacy is similar and increase sponsors' collection of high-quality PRO data in registrational trials.","rationale":"Sponsors collect what regulators read. Making patient experience a labelled claim gives it commercial value and standardises how it is measured.","test":"Regulator pilots the section for all approvals over two years; survey prescribers and measure uptake of PRO instruments in subsequent pivotal protocols.","maturity":"early-clinical","actor":"regulator","cost":"small","horizonYears":3},{"id":"idea-data-silent-trial-before-deployment","kind":"idea","name":"A mandatory silent (shadow) trial before any cancer AI goes live","aka":[],"tldr":"Before an AI tool is allowed to influence care at a hospital, it would run invisibly alongside clinicians for months so its real-world performance at that site is known first.","summary":"Shadow deployment (the model runs on live data but its outputs are hidden and compared with clinicians and outcomes) is standard practice at a few pioneering centres but not required. The proposal makes a pre-specified silent trial (minimum case numbers, pre-declared performance thresholds, subgroup analysis, comparison with local clinicians) a condition of go-live at each site, reported to the registry, as the AI equivalent of laboratory method verification before a new assay is used.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (AI that is built but not validated or deployed): Wu et al., How medical AI devices are evaluated: limitations and recommendations from an analysis of FDA approvals (Nature Medicine 2021)","url":"https://doi.org/10.1038/s41591-021-01312-x"}],"tags":[],"related":["idea-data-drift-monitoring-standard"],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-ai-validation"],"keyPapers":["paper-wu-nat-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Site-level silent trials will identify locally unacceptable performance in a meaningful share of deployments that passed regulatory clearance, preventing harm and building trust at sites where the tool passes.","rationale":"Clinical laboratories must verify every new assay locally before use, because performance depends on local conditions; AI has the same dependence and no equivalent rule.","test":"Require silent trials for all AI deployments in one hospital network for two years; report the proportion failing local thresholds and the reasons.","maturity":"early-clinical","actor":"clinic","cost":"small","horizonYears":1},{"id":"idea-tr1-tumour-board-trial-line-item","kind":"idea","name":"A mandatory trial line in every tumour board recommendation","aka":[],"tldr":"Every time a team of specialists meets to plan a patient's treatment, they would have to record whether a trial exists for that patient and, if so, why it was or was not offered.","summary":"Multidisciplinary tumour boards and molecular tumour boards add a required structured field to their recommendation: matched trials considered (with identifiers), offered yes/no, and reason if not. A trial coordinator pre-populates the field from a matching tool before the meeting. The field is auditable and the offer rate reported quarterly by service.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Trials enrol too few, too slowly): Unger et al., Systematic review of barriers to cancer trial participation (JNCI 2019)","url":"https://doi.org/10.1093/jnci/djy221"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["ai-trial-matching"],"targets":[],"drugs":[],"companies":[],"institutions":["mskcc","royal-marsden","gustave-roussy"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-enrolment"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Making trial consideration a documented step raises the trial offer rate from the typical single digits to over 20 percent of board-discussed patients within a year, and enrolment rises in proportion.","rationale":"Checklists change behaviour where the omission is habitual rather than deliberate. Surgical safety checklists and the 'sepsis six' work through the same mechanism. Tumour boards already have the structure; only the field is missing.","test":"Before-after with contemporaneous control services in two cancer centres; outcome is documented trial offers and enrolments per 100 board discussions.","maturity":"speculative","actor":"clinic","cost":"small","horizonYears":1},{"id":"idea-data-living-llm-oncology-benchmark","kind":"idea","name":"A monthly-updated benchmark for AI answers to oncology questions with citation accuracy","aka":[],"tldr":"Test the large language models doctors and patients are already using against a continually refreshed set of cancer questions, scoring not just correct answers but whether the sources they cite are real and support the claim.","summary":"Clinicians and patients use general-purpose language models for oncology questions; evaluations are static, quickly outdated and rarely check citations. The proposal is a living benchmark: new questions each month drawn from recent practice changes, expert-graded answers, and scoring of citation validity and support, with public leaderboards and per-cancer breakdowns, run by an independent academic consortium.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Knowledge reaches practice too slowly): Morris, Wooding & Grant, The answer is 17 years, what is the question (JRSM 2011)","url":"https://doi.org/10.1258/jrsm.2011.110180"}],"tags":[],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-knowledge-diffusion","b-ai-validation","b-misinformation"],"keyPapers":["paper-morris-j-r-soc-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Public, living evaluation will drive measurable improvement in citation accuracy and currency of oncology answers across models within a year, and will identify failure modes (outdated standards, hallucinated trials) that static benchmarks miss.","rationale":"Public benchmarks have driven progress in every area of machine learning; medical question benchmarks exist but are static and do not test currency, which is the key oncology failure.","test":"Run the benchmark monthly for a year on the major models; publish trends; check whether model releases show improvement on the citation and currency metrics.","maturity":"early-clinical","actor":"research","cost":"small","horizonYears":1},{"id":"idea-bio1-adaptive-therapy-platform","kind":"idea","name":"A multi-cancer platform trial of adaptive (dose-holiday) therapy","aka":[],"tldr":"Instead of hitting a tumour with the maximum dose until it stops working, adjust the dose to keep the tumour small and let drug-sensitive cells suppress resistant ones. Test this properly across several cancers.","summary":"Adaptive therapy, in which dosing is modulated on a tumour burden marker to maintain a stable population of sensitive cells, extended time to progression in a pilot of abiraterone in prostate cancer. It has not been tested at scale or outside prostate. A platform trial would run adaptive versus continuous dosing arms in prostate (PSA), ovarian (CA-125) and melanoma (ctDNA) simultaneously with a shared evolutionary modelling core.","asOf":"2026-09-08","links":[{"label":"Zhang et al., adaptive therapy pilot in prostate cancer (Nat Commun 2017)","url":"https://www.nature.com/articles/s41467-017-01968-5"}],"tags":[],"related":["idea-desmoid-intermittent-dosing"],"cancers":["prostate","ovarian","melanoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["moffitt"],"pathways":[],"terms":["basket-umbrella-platform"],"trials":[],"people":[],"bottlenecks":["b-tumor-heterogeneity","b-dose-optimisation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Adaptive dosing at least doubles time to progression compared with continuous maximum tolerated dosing in at least one of three cancer settings while reducing cumulative drug exposure by 40 percent or more.","rationale":"Evolutionary theory and the prostate pilot agree that maintaining a sensitive population imposes a fitness cost on resistant cells; the failure of continuous dosing to prevent resistance is universal.","test":"Randomised phase 2 platform with 100 patients per disease cohort, primary endpoint time to progression, secondary cumulative dose and quality of life; pre-specified mathematical model calibration per patient.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":5},{"id":"idea-data-national-cancer-data-space","kind":"idea","name":"A national cancer data space with one legal front door","aka":[],"tldr":"Instead of asking twenty hospitals for permission, a researcher would apply once to a single national body that can grant access to all cancer records under one set of rules.","summary":"The European Health Data Space regulation (2025) creates health data access bodies that grant permits for secondary use across all holders in a member state. The proposal is a cancer-specific instance: one permit authority, one data catalogue, one set of standard extraction pipelines (OMOP and mCODE), and statutory deadlines for holders to comply. England's NHS Research Secure Data Environment network and Finland's Findata are working precedents; the US has no equivalent.","asOf":"2026-09-08","links":[{"label":"European Health Data Space","url":"https://health.ec.europa.eu/ehealth-digital-health-and-care/european-health-data-space_en"},{"label":"Findata","url":"https://findata.fi/en/"}],"tags":[],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-data-silos","b-real-world-evidence"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A single-permit cancer data space cuts the median time from research question to approved dataset from more than a year to under 90 days and increases the number of multi-centre real-world studies per year at least threefold.","rationale":"Findata reduced permit times to weeks; the bottleneck in most countries is not technology but the need to negotiate with each data controller separately. Statutory duty to provide data, with a single authority, removes the negotiation.","test":"Track permit time, dataset delivery time and study output for one cancer-focused access body over three years versus the previous multi-controller process in the same country; publish the comparison.","maturity":"early-clinical","actor":"policy","cost":"large","horizonYears":5},{"id":"idea-gbc-national-incidental-cancer-pathway","kind":"idea","name":"A national incidental gallbladder cancer pathway: histology for every gallbladder, referral within two weeks, re-resection by eight","aka":[],"tldr":"About six in every thousand gallbladders removed for stones contain cancer. A written pathway that sends every specimen to the pathologist, refers every T1b or deeper cancer to a liver surgeon within two weeks and books the second operation within eight would turn a lottery into a system.","summary":"Incidental cancer is 0.6 percent of cholecystectomies (Pyo 2020). In the Netherlands only 24 percent of eligible patients were re-resected (2020); in the UK CAPBIL cohort 67.7 percent had liver resection (2026), with the reasons for the rest unknown. Observational data favour re-resection at four to eight weeks (Ethun 2017) though a 2026 individual patient data meta-analysis found timing did not change survival, so the pathway should prioritise completion over speed. Selective histology policies risk missing cancers (Khan 2021 systematic review). A national pathway with audit, the model the NHS uses for other two-week-wait cancers, needs no new drug and could be measured through existing registries.","asOf":"2026-09-24","links":[{"label":"de Savornin Lohman et al.: re-resection rate 24 percent in the Netherlands (Ann Surg Oncol 2020)","url":"https://europepmc.org/article/MED/31741109"},{"label":"CAPBIL: 67.7 percent liver resection across 24 UK centres (Br J Surg 2026)","url":"https://europepmc.org/article/MED/42013358"},{"label":"Khan et al.: selective versus routine histology of cholecystectomy specimens, systematic review (Asian Pac J Cancer Prev 2021)","url":"https://europepmc.org/article/MED/33773526"}],"tags":["gallbladder-evidence"],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["incidental-gallbladder-cancer","radical-cholecystectomy"],"trials":["opt-in"],"people":[],"bottlenecks":["b-care-fragmentation","b-knowledge-diffusion"],"keyPapers":["paper-pyo-incidental-gallbladder-cancer-meta-analysis-jcm-2020","paper-de-savornin-lohman-re-resection-incidental-gallbladder-cancer-aso-2020","paper-mcclements-capbil-incidental-gallbladder-cancer-bjs-2026","paper-ethun-re-resection-timing-incidental-gallbladder-cancer-jama-surg-2017","paper-selvakumar-revision-surgery-timing-ipd-meta-analysis-hpb-2026"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A mandated pathway (routine histology, two-week referral of T1b or deeper incidental cancers to a hepatobiliary multidisciplinary team, re-resection within eight weeks where fit) will raise the proportion of eligible patients re-resected to above 80 percent and be associated with longer disease-free survival at national level.","rationale":"The intervention with the largest observed survival association in incidental gallbladder cancer is completing the radical operation; the largest documented failure is not reaching it.","test":"Stepped-wedge implementation across hepatobiliary networks with registry-linked outcomes (re-resection rate, interval, R0 rate, disease-free survival), benchmarked against the CAPBIL 2014 to 2022 baseline.","maturity":"early-clinical","actor":"clinic","cost":"small","horizonYears":4},{"id":"idea-acc-national-late-effects-registry","kind":"idea","name":"A national late-effects registry linking treatment exposures to outcomes decades later","aka":[],"tldr":"We know surprisingly little about what happens to cancer survivors twenty years on. Linking their treatment records to later health records would show which treatments cause which problems and who needs watching.","summary":"Childhood cancer survivor cohorts (CCSS in the US, BCCSS in the UK, DCOG-LATER in the Netherlands) transformed understanding of late effects. Adult survivors have no equivalent at scale. A national registry linking cancer registry treatment data (including radiotherapy doses and cumulative drug doses) to hospital, prescribing, and mortality records would generate late-effect risks for modern therapies, including immunotherapy and targeted agents, whose long-term effects are unknown.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Survivorship and late effects are neglected): NCI Office of Cancer Survivorship statistics","url":"https://cancercontrol.cancer.gov/ocs/statistics"}],"tags":[],"related":["seer"],"cancers":[],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-real-world-evidence","b-data-silos"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Within five years, linked registry data will quantify late cardiovascular, endocrine, and second-cancer risks for at least ten contemporary regimens with sufficient precision to change surveillance guidelines.","rationale":"Nordic and Dutch linkage studies show that registry linkage yields robust late-effect estimates at low cost relative to cohort studies.","test":"Establish linkage in one country with strong registries, publish first risk estimates within three years, and track adoption into surveillance guidelines.","maturity":"early-clinical","actor":"data","cost":"medium","horizonYears":5},{"id":"idea-fund-public-nonprofit-cro","kind":"idea","name":"A national non-profit contract research organisation for academic oncology trials","aka":[],"tldr":"Running an early trial properly requires monitors, data managers, safety reporting and regulatory filings that universities cannot afford from commercial providers. A public not-for-profit would do this work at cost.","summary":"A publicly-owned or non-profit CRO providing sponsor-level services (protocol development, regulatory submissions, monitoring, pharmacovigilance, data management, statistics) to academic phase 1 and 2 oncology trials at cost, funded partly by a core grant and partly by fees charged to grants. Academic trials fail or stall for operational, not scientific, reasons; commercial CRO fees consume a large share of academic trial budgets. Precedents include the UK's NIHR clinical research network infrastructure, the EORTC headquarters model for European academic trials, and NCI's CTEP for investigational agents.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The valley of death between lab and product): Butler, Translational research: crossing the valley of death (Nature 2008)","url":"https://doi.org/10.1038/453840a"}],"tags":[],"related":["idea-fund-translational-institutes-gmp","idea-fund-global-academic-phase-one-network"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["curie-nki-eortc"],"institutions":["nci"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-translational-valley","b-trial-design"],"keyPapers":["paper-reproducibility-project-cancer-biology-elife-2021","paper-butler-nature"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Academic trials supported by a non-profit CRO complete recruitment and report results at least 30% faster than academic trials using commercial or in-house ad hoc support, at lower total cost per patient.","rationale":"EORTC and the German and UK cooperative trials units show that shared professional infrastructure lifts completion rates and quality; a non-profit CRO extends this from cooperative-group phase 3 to the early-phase academic trials where the valley of death is deepest.","test":"Fund a pilot CRO to sponsor twenty academic phase 1/2 oncology trials and compare start-up time, recruitment velocity, protocol deviations and reporting time against a matched set of contemporaneous academic trials.","maturity":"speculative","actor":"policy","cost":"large","horizonYears":4},{"id":"idea-bio2-national-mrd-platform","kind":"idea","name":"A national platform trial that every ctDNA-positive patient can join","aka":[],"tldr":"Blood tests can now find leftover cancer months before scans, but most patients who test positive have nothing to enrol in. One standing trial per country would fix that.","summary":"MRD-guided intervention has proved feasible in bladder cancer and colorectal cancer, but each trial rebuilds the same infrastructure: assay contracts, testing schedules, referral pathways and consent. A standing national platform (one master protocol, shared control arm, rolling arms contributed by any sponsor, registry-based follow-up) converts a scattered set of underpowered studies into a permanent engine for the MRD setting.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Dormant cells and minimal residual disease): Tie et al., ctDNA analysis guiding adjuvant therapy in stage II colon cancer (NEJM 2022)","url":"https://doi.org/10.1056/NEJMoa2200075"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["mrd-testing","ai-trial-matching"],"targets":[],"drugs":[],"companies":["ecog-acrin"],"institutions":["nci","cruk"],"pathways":[],"terms":["basket-umbrella-platform","mrd"],"trials":["imvigor011","dynamic","circulate-japan"],"people":[],"bottlenecks":["b-dormancy-mrd","b-trial-design","b-trial-enrolment"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A national MRD platform doubles the proportion of ctDNA-positive patients enrolled in an interventional trial within three years and reduces the cost per randomised patient by half compared with standalone MRD trials.","rationale":"Platform infrastructure has repeatedly outperformed serial standalone trials in speed and cost, as seen in adaptive platforms in breast cancer and in pandemic therapeutics. The MRD setting is unusually well suited because the eligibility test is a single blood assay.","test":"Stand up the platform in one tumour type with two arms and a shared control, and measure enrolment rate, time from positive test to randomisation, and cost per randomised patient against historical standalone MRD trials.","maturity":"being-tested-at-scale","actor":"policy","cost":"large","horizonYears":5},{"id":"idea-bio1-rapid-autopsy-network","kind":"idea","name":"A national rapid research autopsy network for end-stage cancer","aka":[],"tldr":"When patients who agreed in advance die of cancer, sampling every tumour within hours reveals how the disease evolved and escaped every drug. Few hospitals can do this today.","summary":"Programmes such as PEACE (UK) and CASCADE (Australia) recruit patients in life for post-mortem multi-site sampling within six hours. The proposal is to fund a standing network with 24-hour on-call pathology, consent embedded in oncology clinics, and a common sample and data model, so that terminal clonal architecture becomes a routine, shareable dataset rather than a rarity.","asOf":"2026-09-08","links":[{"label":"PEACE study (NCT03004755)","url":"https://clinicaltrials.gov/study/NCT03004755"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["wes-wgs","single-cell-spatial"],"targets":[],"drugs":[],"companies":[],"institutions":["francis-crick","peter-mac","cruk"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-tumor-heterogeneity","b-metastasis-biology"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A network processing 500 rapid autopsies a year yields, within five years, a catalogue of metastatic clonal architectures and resistance mechanisms that identifies at least ten recurrent, druggable terminal dependencies not visible in diagnostic biopsies.","rationale":"Terminal disease is the disease that kills; it is almost never sequenced. Rapid autopsy cohorts have already revealed polyclonal seeding, metastasis-to-metastasis spread and convergent resistance evolution.","test":"Fund three regional hubs with a shared protocol for two years; measure consent rate, time-to-sampling, sample quality, and the number of novel resistance mechanisms per 100 cases versus the published rate from progression biopsies.","maturity":"early-clinical","actor":"philanthropy","cost":"medium","horizonYears":4},{"id":"idea-data-radiotherapy-dose-repository","kind":"idea","name":"A national repository of radiotherapy dose plans linked to outcomes","aka":[],"tldr":"Radiotherapy machines record exactly how much dose every organ received, but the data are thrown away. Collect them and link to toxicities and cures to learn the safest, most effective doses.","summary":"Every treated patient has a DICOM-RT plan with voxel-level dose to tumour and organs at risk. Pooled with outcomes, this supports data-driven dose constraints, toxicity models and quality benchmarking. The Netherlands and the English Radiotherapy Dataset have partial national data; the proposal makes automated plan deposition (DICOM-RT structures and dose) plus registry linkage universal, with governed access for research and quality improvement.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Data silos): AACR Project GENIE","url":"https://www.aacr.org/professionals/research/aacr-project-genie/"}],"tags":[],"related":[],"cancers":[],"sections":["ai-computation","radiation"],"technologies":["imrt-igrt","proton-therapy"],"targets":[],"drugs":[],"companies":["varian","elekta"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-data-silos","b-surgery-radiation-innovation","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A national dose-outcome repository will yield updated normal-tissue tolerance models within three years and reduce grade 3 or higher toxicity in at least one common site through revised constraints within five.","rationale":"Radiotherapy is one of the most data-rich treatments and the least analysed; QUANTEC constraints rest on small series decades old. Dose-outcome modelling is a mature methodology waiting for data.","test":"Deposit plans from ten centres for one disease (for example head and neck) and model dysphagia and xerostomia against dose; compare with existing constraints and validate prospectively.","maturity":"early-clinical","actor":"clinic","cost":"medium","horizonYears":3},{"id":"idea-moon-mrd-weather-service","kind":"idea","name":"A national residual-disease weather service: serial blood tests for every curatively treated patient, pooled","aka":[],"tldr":"After surgery or curative treatment, everyone gets regular blood tests for leftover cancer DNA, and the pooled results power forecasts of who will relapse and trials of acting early.","summary":"Circulating tumour DNA detects molecular residual disease months before imaging, and trials such as DYNAMIC and IMvigor011 show it can guide adjuvant decisions. Uptake is piecemeal and results are not pooled. The proposal is a national programme offering serial MRD testing to all patients treated with curative intent for high-risk cancers, with data flowing to a shared platform that continuously estimates relapse risk, feeds MRD-triggered trial randomisation, and reports test performance by tumour type and assay.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Dormant cells and minimal residual disease): Tie et al., ctDNA analysis guiding adjuvant therapy in stage II colon cancer (NEJM 2022)","url":"https://doi.org/10.1056/NEJMoa2200075"}],"tags":[],"related":["idea-ctdna-escalation-tnbc"],"cancers":["colorectal","urothelial","tnbc"],"sections":[],"technologies":["mrd-testing","liquid-biopsy"],"targets":[],"drugs":["signatera"],"companies":[],"institutions":[],"pathways":[],"terms":["mrd","ctdna"],"trials":["dynamic","imvigor011"],"people":[],"bottlenecks":["b-dormancy-mrd","b-real-world-evidence"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Universal MRD surveillance with pooled analytics increases the proportion of relapses detected at molecular stage to over 70%, enables MRD-triggered trials that improve cure rates, and reduces unnecessary adjuvant therapy in MRD-negative patients.","rationale":"Early intervention on minimal disease is more likely to cure than treating bulk relapse; assays are validated and the marginal cost of testing is falling. Pooling turns each patient into evidence.","test":"Regional programme in colorectal, bladder and breast cancer with embedded randomised MRD-triggered treatment and de-escalation arms; endpoints molecular-stage detection rate and disease-free survival.","maturity":"early-clinical","actor":"data","cost":"large","horizonYears":5},{"id":"idea-fund-rt-io-platform","kind":"idea","name":"A neutral platform trial for radiotherapy plus immunotherapy combinations","aka":[],"tldr":"Radiotherapy may make immunotherapy work better, but the trials to test this are scattered and often small. One shared platform, run by radiotherapy groups with drugs supplied by several companies, would settle it faster.","summary":"A master protocol operated by academic radiotherapy groups (through a neutral sponsor) in which multiple companies' immunotherapies are tested in combination with standardised radiotherapy schedules, doses and target volumes across defined indications (oligometastatic disease, locally advanced head and neck, lung, bladder), with a shared control arm and pre-specified translational sampling. Existing RT-IO trials use inconsistent radiotherapy, making negative and positive results hard to interpret. Radiotherapy groups have the trial infrastructure but no access to drugs; companies have drugs but do not prioritise radiotherapy combinations, so the pairing is a natural public-private platform.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Surgery and radiotherapy cure most, get least): Sullivan et al., Global cancer surgery (Lancet Oncology Commission 2015)","url":"https://doi.org/10.1016/S1470-2045(15)00223-5"}],"tags":[],"related":["radiation-plus-io","idea-fund-neutral-platform-sponsor","idea-fund-radiotherapy-trials-infrastructure"],"cancers":[],"sections":[],"technologies":["sbrt","checkpoint-inhibitor","imrt-igrt"],"targets":[],"drugs":["durvalumab","pembrolizumab","nivolumab"],"companies":[],"institutions":[],"pathways":[],"terms":["abscopal-effect","oligometastatic","basket-umbrella-platform"],"trials":[],"people":["kevin-harrington"],"bottlenecks":["b-surgery-radiation-innovation","b-ip-collaboration","b-combination-space"],"keyPapers":["paper-sullivan-lancet-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A neutral RT-IO platform evaluates at least six immunotherapy agents with standardised radiotherapy within four years and produces at least one positive signal warranting phase 3 and at least two clear negatives, at a per-agent cost below a third of stand-alone RT-IO trials.","rationale":"PACIFIC showed the value of sequencing immunotherapy after chemoradiotherapy; many subsequent trials with poorly standardised radiotherapy have been negative or uninterpretable. Platform designs have worked in glioblastoma and breast cancer; combining them with radiotherapy quality assurance is the missing step.","test":"Launch the platform in one indication with three agents and a shared control, and report activation time, standardisation compliance and per-agent cost against recent stand-alone trials.","maturity":"early-clinical","actor":"research","cost":"large","horizonYears":4},{"id":"idea-data-neutral-ai-evaluator","kind":"idea","name":"A neutral public evaluator for cancer AI, on the model of NIST","aka":[],"tldr":"Create an independent public body whose job is to test cancer AI tools against each other on locked-away data and publish the scores, so hospitals can buy on evidence.","summary":"Hospitals cannot compare AI vendors; each presents its own validation. A publicly funded evaluator, running the sequestered benchmarks, publishing head-to-head results, subgroup performance and robustness tests, and updating as models change, would make procurement evidence-based and give regulators an independent data source. Models exist in NIST's testing programmes and the UK's AI evaluation initiatives.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (AI that is built but not validated or deployed): Wu et al., How medical AI devices are evaluated: limitations and recommendations from an analysis of FDA approvals (Nature Medicine 2021)","url":"https://doi.org/10.1038/s41591-021-01312-x"}],"tags":[],"related":["idea-data-sequestered-prospective-benchmarks"],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-ai-validation"],"keyPapers":["paper-wu-nat-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Publication of independent head-to-head results will shift procurement toward better-performing models and cause under-performing products to leave the market within three years.","rationale":"Independent testing works where buyers cannot verify claims themselves (cars, appliances, biometrics); cancer AI has exactly this information asymmetry.","test":"Fund the evaluator to test one task (mammography AI) across all vendors; survey procurement decisions in the following two years for reference to the results.","maturity":"speculative","actor":"policy","cost":"medium","horizonYears":3},{"id":"idea-reg-manufacturing-slot-exchange","kind":"idea","name":"A neutral slot exchange so unused CAR-T manufacturing slots go to the next patient","aka":[],"tldr":"Patients wait weeks for a manufacturing slot while other slots go unused when a patient drops out. A shared booking system would match spare slots to waiting patients.","summary":"CAR-T manufacturing slots are allocated per product and per treatment centre, and cancellations (patient deterioration, failed apheresis) leave slots empty while patients at other centres wait. The proposal is a neutral, regulator-sanctioned exchange, run by a registry organisation, where manufacturers post real-time slot availability and treatment centres release and claim slots across products and sites, with priority rules agreed by clinicians. It resembles organ allocation and airline seat inventory systems.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Manufacturing cost and time for living and radioactive medicines): Hernandez, Prasad & Gellad, Total costs of chimeric antigen receptor T-cell immunotherapy (JAMA Oncology 2018)","url":"https://doi.org/10.1001/jamaoncol.2018.0977"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["car-t"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-manufacturing-cell-therapy","b-care-fragmentation"],"keyPapers":["paper-hernandez-jama-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"An exchange reduces median time from referral to apheresis by at least a week and increases slot utilisation above 90%, reducing the proportion of eligible patients who never reach infusion.","rationale":"The queue is a matching problem; the current fragmentation means aggregate capacity exceeds aggregate demand in many months while individual patients still wait. Slot utilisation data are already collected by manufacturers.","test":"Pilot the exchange in one country with two manufacturers and ten centres for a year; compare referral-to-apheresis interval and slot utilisation with the prior year.","maturity":"speculative","actor":"data","cost":"small","horizonYears":2},{"id":"idea-reg-nonprofit-marketing-authorisation-holder","kind":"idea","name":"A non-profit company to hold marketing authorisations for repurposed cancer drugs","aka":[],"tldr":"Someone must legally own a drug's licence to update its label and monitor safety. A non-profit could do this for old drugs proven to work in cancer that no company wants.","summary":"Regulatory systems assume a commercial marketing authorisation holder who files variations, maintains pharmacovigilance and supplies the product. For repurposed generics, no such holder has an incentive to act. Non-profit developers (Medicines Development for Global Health, DNDi, Cures Within Reach) have shown that non-profits can hold authorisations and run pharmacovigilance. The proposal is a non-profit oncology authorisation holder, funded by the repurposing fund and payers, that files new-indication applications, holds labels for repurposed generics, contracts manufacturing from generic makers, and runs the required safety monitoring.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (No incentive to repurpose cheap drugs): Pantziarka et al., The Repurposing Drugs in Oncology (ReDO) Project (ecancer 2014)","url":"https://doi.org/10.3332/ecancer.2014.442"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-generic-repurposing","b-regulatory-fragmentation"],"keyPapers":["paper-pantziarka-ecancermedicalscience"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"The non-profit holder secures labelled oncology indications for at least three repurposed drugs within five years and maintains supply at generic prices, with pharmacovigilance meeting regulatory standards.","rationale":"The gap is institutional rather than scientific or financial: someone must be the accountable holder. A purpose-built non-profit fills the role at low cost and removes the dependence on unwilling commercial holders.","test":"Incorporate the entity, take on one repurposed indication with completed phase 3 evidence, and file in two regions; report time to approval and running costs.","maturity":"speculative","actor":"philanthropy","cost":"medium","horizonYears":4},{"id":"idea-reg-nonprofit-generic-chemo-manufacturer","kind":"idea","name":"A non-profit manufacturer for generic cancer drugs in chronic shortage","aka":[],"tldr":"Cheap, essential chemotherapy drugs like cisplatin run out because making them is not profitable enough. A non-profit maker could guarantee supply at a fair price.","summary":"The 2023 US shortages of cisplatin and carboplatin, and recurrent shortages of methotrexate, vincristine and other generic oncology drugs, arise from thin margins, concentrated manufacturing and quality failures at single plants. Civica Rx, a non-profit founded by US health systems, has shown that a mission-driven manufacturer with long-term hospital contracts can stabilise supply of generic hospital injectables. The proposal is a non-profit oncology generics manufacturer or a Civica oncology division, with multi-year purchase commitments from health systems and dual-sourced active ingredients, initially for the ten most shortage-prone oncology injectables.","asOf":"2026-09-08","links":[{"label":"Civica Rx","url":"https://civicarx.org/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["cytotoxic-chemotherapy","platinum"],"targets":[],"drugs":["carboplatin","paclitaxel"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-drug-pricing","b-global-access"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Health systems contracting with the non-profit manufacturer experience at least 80% fewer shortage days for covered oncology drugs and pay prices within 20% of prevailing generic prices.","rationale":"Shortages are a market failure of under-investment in redundancy for low-margin products; a manufacturer whose objective is supply reliability rather than margin, backed by demand guarantees, corrects the incentive.","test":"Fund production of five shortage-prone oncology injectables with commitments from 50 hospitals and track shortage days and prices against national shortage data for three years.","maturity":"early-clinical","actor":"philanthropy","cost":"large","horizonYears":3},{"id":"idea-cost-nonprofit-generic-oncology","kind":"idea","name":"A non-profit manufacturer for shortage-prone generic chemotherapy","aka":[],"tldr":"Cisplatin and carboplatin cost a few dollars a dose yet ran short across the US in 2023 because too few makers found them worth producing; a non-profit maker with long-term hospital contracts would keep them on the shelf.","summary":"Civica Rx showed that a hospital-owned non-profit can manufacture and stock essential generics under long-term, fixed-price contracts, stabilising supply of sterile injectables. Oncology generics (platinums, fluorouracil, methotrexate, vincristine) are cheap, old and shortage-prone because thin margins push manufacturers out. A dedicated oncology line, funded by hospital consortia and philanthropy, would hold safety stock and dual-source active ingredients. The saving is not the drug price but the avoided cost of substitution, delay and dearer alternatives when a shortage hits.","asOf":"2026-09-10","links":[{"label":"Civica Rx","url":"https://civicarx.org/"},{"label":"FDA: drug shortages","url":"https://www.fda.gov/drugs/drug-safety-and-availability/drug-shortages"}],"tags":[],"related":[],"cancers":[],"sections":["chemotherapy"],"technologies":["cytotoxic-chemotherapy","platinum"],"targets":[],"drugs":["cisplatin","carboplatin"],"companies":["civica-rx"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-drug-pricing","b-global-access"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A non-profit oncology generics supplier holding six months of inventory for the ten most shortage-prone cytotoxics will cut shortage days for those drugs among member hospitals by more than 80% within three years.","rationale":"The 2023 platinum shortage forced dose changes and substitutions in most US cancer centres; the fix is a supply model, not a scientific one.","test":"Member hospitals report shortage days, substitutions and spending on alternatives, compared with non-member hospitals in the same regions.","maturity":"early-clinical","actor":"philanthropy","cost":"large","horizonYears":4},{"id":"idea-fund-nonprofit-pharma","kind":"idea","name":"A non-profit pharmaceutical company for the cancers markets ignore","aka":[],"tldr":"Build a drug company that does not need profits, modelled on the ones that developed new tuberculosis and sleeping-sickness drugs, to take on rare, paediatric and undruggable cancers.","summary":"A product development partnership (PDP) for oncology, on the model of the Drugs for Neglected Diseases initiative, TB Alliance and Medicines for Malaria Venture: philanthropic and public core funding, in-licensing of shelved or academic assets, virtual development through contract organisations, trials run with academic networks, and pricing at cost plus a margin reinvested in the pipeline. Target areas are those where the commercial case is weak but the science is ready: paediatric solid tumours, rare fusion-driven cancers, repurposed generics, and de-escalation regimens. The PDP can also be the licensee of last resort for assets that companies abandon.","asOf":"2026-09-08","links":[{"label":"Drugs for Neglected Diseases initiative","url":"https://dndi.org/"},{"label":"TB Alliance","url":"https://www.tballiance.org/"}],"tags":[],"related":["idea-fund-amc-paediatric-rare","idea-fund-shelved-asset-escrow","idea-fund-repurposing-indication-exclusivity"],"cancers":["neuroblastoma","sarcoma","cholangiocarcinoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-incentive-misalignment","b-rare-cancers","b-translational-valley"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"An oncology PDP funded at $100 to $200 million a year brings at least three products to registration within a decade in indications with no commercial programme, at development costs under a third of industry averages.","rationale":"DNDi has delivered multiple approved treatments (fexinidazole for sleeping sickness among them) and TB Alliance delivered pretomanid, at a fraction of industry costs, by combining donor funding with in-licensing and academic trial networks. Oncology has large philanthropic flows but no comparable development vehicle.","test":"Seed a PDP with two in-licensed assets and one repurposing programme; success at year five is one asset in a registration trial and a documented cost per phase.","maturity":"speculative","actor":"philanthropy","cost":"large","horizonYears":8},{"id":"idea-tr2-combination-utility","kind":"idea","name":"A non-profit phase 1b combination unit that any drug owner can use","aka":[],"tldr":"Build a shared, not-for-profit clinical unit that runs early combination trials to a standard recipe, so that small companies and academics can test pairs without building their own trial machinery.","summary":"Early combination trials repeat the same work: pharmacokinetic interaction, overlapping toxicity, dose finding. A utility unit with standard protocols, pre-negotiated site contracts and a fixed price per arm (analogous to a contract research organisation but mission-driven and data-open) would lower the barrier for combinations that no single company will sponsor, especially those pairing drugs from different owners.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Too many combinations to test): Palmer & Sorger, Combination cancer therapy can confer benefit via patient-to-patient variability without drug additivity or synergy (Cell 2017)","url":"https://doi.org/10.1016/j.cell.2017.11.009"}],"tags":[],"related":["cruk","royal-marsden","icr-london","idea-tr2-public-combination-formulary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-combination-space","b-translational-valley"],"keyPapers":["paper-palmer-cell"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"The unit will run combination phase 1b arms at less than half the cost and time of industry-sponsored equivalents and will publish every result, positive or negative, within a year of completion.","rationale":"Shared infrastructure works elsewhere in science (synchrotrons, sequencing centres). The UK Experimental Cancer Medicine Centres show the model at national scale.","test":"Fund a unit for five years with a mandate of twenty combination arms; audit cost, time and publication rate against matched industry trials.","maturity":"speculative","actor":"philanthropy","cost":"large","horizonYears":4},{"id":"idea-acc-paediatric-palliative-in-every-childhood-unit","kind":"idea","name":"A paediatric palliative care team in every childhood cancer unit","aka":[],"tldr":"Children with cancer, and their families, need symptom relief and support from diagnosis, not only at the end. Every children's cancer unit should have a palliative team, and most in poorer countries have none.","summary":"Paediatric palliative care improves symptom control and family outcomes and does not shorten life, yet most childhood cancer units globally lack a dedicated team, and referral is often late. Integrating a small team (nurse, doctor with training, psychosocial support) into every paediatric oncology unit, with early involvement for high-risk diagnoses, is feasible at modest cost and is a stated aim of the WHO Global Initiative for Childhood Cancer.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Pain relief and palliative care are unavailable to most): WHO fact sheet, Palliative care","url":"https://www.who.int/news-room/fact-sheets/detail/palliative-care"}],"tags":[],"related":[],"cancers":["all-leukemia","neuroblastoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-palliative","b-rare-cancers","b-global-access"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Units with an integrated paediatric palliative team will improve parent-reported symptom control and reduce intensive interventions in the last week of life, with no reduction in curative-intent treatment completion.","rationale":"Adult early palliative care evidence and paediatric cohort studies point the same direction; the gap is workforce and funding.","test":"Implementation in 20 units across income levels with parent-reported outcomes, end-of-life care intensity, and staff wellbeing as endpoints.","maturity":"early-clinical","actor":"philanthropy","cost":"medium","horizonYears":3},{"id":"idea-acc-funded-navigator-per-diagnosis","kind":"idea","name":"A paid patient navigator for every new cancer diagnosis, reimbursed as a service","aka":[],"tldr":"Every newly diagnosed patient gets a named person whose job is to get them through appointments, tests, paperwork and money problems. Insurers should pay for it because it prevents delays and dropouts.","summary":"Patient navigation programmes improve time to treatment and completion, particularly for disadvantaged groups, and randomised evidence exists. In the US, Medicare began paying for principal illness navigation services in 2024, creating a reimbursement route. Elsewhere navigation depends on charity funding. The proposal is to make navigation a reimbursed service from diagnosis to end of treatment, with standard training, caseloads, and outcome reporting.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Fragmented care and guideline gaps): Hanna et al., Mortality due to cancer treatment delay: systematic review and meta-analysis (BMJ 2020)","url":"https://doi.org/10.1136/bmj.m4087"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-care-fragmentation","b-patient-voice","b-trial-diversity"],"keyPapers":["paper-hanna-bmj"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Universal funded navigation will reduce time from diagnosis to first treatment by at least 20% and reduce the gap in treatment completion between the most and least deprived quintiles by half.","rationale":"Navigation addresses the practical barriers (transport, scheduling, understanding, cost) that cause delays; it works best when it is a paid role rather than a volunteer one.","test":"A payer-level pilot in two regions with time to treatment, completion, emergency visits, and cost offsets as endpoints against matched non-pilot regions.","maturity":"being-tested-at-scale","actor":"payer","cost":"medium","horizonYears":3},{"id":"idea-tr2-combination-patent-pool","kind":"idea","name":"A patent pool for combination method-of-use claims","aka":[],"tldr":"Companies fear that testing a combination will hand a competitor a patent. A shared pool where combination patents are cross-licensed by default would remove the fear.","summary":"Method-of-use patents on combinations create a hold-up problem: whoever runs the trial may end up owing royalties to the other party or blocking them. Patent pools solved similar problems in DVD and telecoms standards. An oncology combination pool, entered voluntarily with fair, reasonable and non-discriminatory terms, would make combination discovery pre-competitive.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Too many combinations to test): Palmer & Sorger, Combination cancer therapy can confer benefit via patient-to-patient variability without drug additivity or synergy (Cell 2017)","url":"https://doi.org/10.1016/j.cell.2017.11.009"}],"tags":[],"related":["idea-tr2-combination-template-agreement"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-combination-space","b-ip-collaboration"],"keyPapers":["paper-palmer-cell"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Pool members will initiate at least 50% more cross-company combination trials in the three years after joining than in the three years before.","rationale":"Pre-competitive consortia (the Structural Genomics Consortium, TransCelerate) have shown that pharma will pool where IP fear is removed and the benefit is shared.","test":"Convene a pool with five sponsors and a neutral administrator; track combination trial initiations and licensing disputes over three years.","maturity":"speculative","actor":"industry","cost":"small","horizonYears":3},{"id":"idea-data-patient-held-cancer-record","kind":"idea","name":"A patient-held cancer record that travels across providers and borders","aka":[],"tldr":"Patients would carry their full cancer history, scans and test results in a standard digital bundle they control and can hand to any doctor anywhere.","summary":"Patients see multiple providers across systems and countries; records do not follow them. A FHIR-based, patient-held record (International Patient Summary plus mCODE bundle, images via DICOMweb links) stored in a patient-controlled vault would make the patient the integration point. Apple Health records, the EU patient summary, and Blue Button show pieces exist; oncology-specific completeness (staging, regimens, genomics, imaging) is missing.","asOf":"2026-09-08","links":[{"label":"International Patient Summary (HL7)","url":"https://hl7.org/fhir/uv/ips/"}],"tags":[],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":["patient-data-vault"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-data-silos","b-care-fragmentation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Patients with a complete portable record will experience fewer repeated tests and faster second opinions, and consented export from these vaults will become a significant source of research data.","rationale":"Where patients hold the record, fragmentation between providers stops being a technical problem; the patient becomes the consent and integration authority.","test":"Provide the record to 500 patients with metastatic disease seen across two or more systems; measure repeat imaging, time to second opinion, and patient-reported burden versus matched controls.","maturity":"early-clinical","actor":"patients","cost":"medium","horizonYears":3},{"id":"idea-moon-patient-held-cancer-record","kind":"idea","name":"A patient-owned, portable complete cancer record in a standard format","aka":[],"tldr":"Your entire cancer history, including scans, pathology, genomics and treatments, lives in a record you control and can share in one click with any hospital, trial or second-opinion service.","summary":"Records are trapped in institutional systems; patients carry paper and CDs to second opinions. The mCODE (minimal Common Oncology Data Elements) FHIR standard now defines the core cancer data set. The proposal is a patient-held record service that pulls mCODE data from every provider under patient consent, stores it under the patient's control, and exposes it to trial-matching, research donation and clinicians the patient chooses. Regulators would require providers to export mCODE on request.","asOf":"2026-09-08","links":[{"label":"mCODE initiative","url":"https://mcodeinitiative.org/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["patient-data-vault"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-patient-voice","b-data-silos"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Patients with portable records obtain second opinions and trial matches faster, experience fewer duplicated tests, and contribute to research at higher rates than those without.","rationale":"Banking and travel solved portability with standards and legal rights of access; oncology has the standard and, in many jurisdictions, the legal right, but no product. The patient is the only actor with a consistent interest in the complete record.","test":"Pilot with three health systems and one trial-matching service: measure completeness of assembled records, time to second opinion, duplicated imaging and consent-to-research rates versus controls.","maturity":"early-clinical","actor":"data","cost":"medium","horizonYears":3},{"id":"idea-fund-neutral-platform-sponsor","kind":"idea","name":"A permanent neutral non-profit sponsor for multi-company platform trials","aka":[],"tldr":"Platform trials that test several companies' drugs against one shared control arm, such as I-SPY 2, Lung-MAP, GBM AGILE and STAMPEDE, are each built from scratch by determined individuals. A permanent non-profit sponsor holding the protocol, control arm, statistics and data, with a standard entry contract for companies, would cut the launch of a new platform from years to months.","summary":"A permanent, funded, non-profit organisation that acts as regulatory sponsor and operator for master protocols in which multiple companies contribute agents, on the model of QuantumLeap Healthcare Collaborative (I-SPY 2), the Lung-MAP public-private partnership, GBM AGILE and the UK's STAMPEDE. The sponsor holds the protocol, the shared control arm, the statistical engine and the data, and offers companies a standard entry contract with pre-agreed rights to use platform results for registration. Each platform today is built from scratch by heroic individuals; institutionalising the function lowers the cost and time of adding a new disease platform from years to months.","asOf":"2026-09-08","links":[{"label":"I-SPY Trials (QuantumLeap Healthcare Collaborative)","url":"https://www.ispytrials.org/"},{"label":"Lung-MAP","url":"https://www.lung-map.org/"}],"tags":[],"related":["idea-fund-combination-patent-pool","idea-fund-control-arm-commons","idea-fund-rt-io-platform"],"cancers":["glioblastoma","pancreatic","tnbc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["swog"],"institutions":[],"pathways":[],"terms":["basket-umbrella-platform"],"trials":[],"people":[],"bottlenecks":["b-ip-collaboration","b-combination-space","b-trial-design"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A standing neutral sponsor launches at least five new disease platforms within four years, each enrolling multiple company-owned agents, and reduces per-agent evaluation cost and time by at least a third relative to stand-alone phase 2 trials of the same agents.","rationale":"I-SPY 2 graduated several agents to phase 3 and informed approvals at a fraction of stand-alone trial cost; GBM AGILE and Lung-MAP demonstrate industry willingness to participate under neutral sponsorship. The bottleneck is the absence of a durable institution, not of willing companies.","test":"Fund the sponsor for five years with a mandate to launch platforms in three under-served indications; report agents evaluated, time to activation and cost per agent against historical stand-alone trials.","maturity":"being-tested-at-scale","actor":"philanthropy","cost":"medium","horizonYears":3},{"id":"idea-moon-supportive-care-platform-trial","kind":"idea","name":"A permanent platform trial for supportive-care interventions inside cooperative groups","aka":[],"tldr":"Instead of one-off small studies, run a standing trial that continuously tests new treatments for side-effects, adding and dropping arms as evidence arrives.","summary":"Supportive-care trials are typically small, single-question and slow. Platform designs have accelerated oncology drug development (I-SPY, STAMPEDE). The proposal is a standing platform in the cooperative groups for symptom interventions (nausea, neuropathy, fatigue, mucositis, dermatologic toxicity), with common PRO endpoints, shared control arms and adaptive randomisation, embedded in routine care to keep costs low.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Toxicity and quality of life are undervalued): Di Maio et al., Symptomatic toxicities experienced during anticancer treatment: agreement between patient and physician reporting (JCO 2015)","url":"https://doi.org/10.1200/JCO.2014.57.9334"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["basket-umbrella-platform"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol","b-trial-design"],"keyPapers":["paper-di-maio-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"The platform tests three times as many interventions per year as the current portfolio at lower cost per question and produces practice-changing results within three years of launch.","rationale":"Shared infrastructure and common endpoints are exactly what supportive care lacks; the cooperative groups already have the sites and the patients.","test":"Launch with four arms in two symptom domains and compare throughput, cost per completed comparison and time to guideline change against the preceding decade of supportive-care trials.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":4},{"id":"idea-fund-surgical-trials-network","kind":"idea","name":"A permanently funded international network for randomised cancer surgery trials","aka":[],"tldr":"Surgery cures more cancer than any drug, yet most operations have never been compared in a proper trial. A standing network of hospitals, with core funding, would run those trials continuously.","summary":"A surgical oncology trials network with core funding for trial units, research nurses and data managers at fifty to one hundred hospitals, standing ethics and contracting arrangements, surgeon credentialling and quality assurance (video review, specimen audit), and a pipeline of pragmatic randomised trials on extent of resection, lymphadenectomy, minimally invasive versus open approaches, timing relative to systemic therapy and organ preservation. The UK's NIHR surgical trials centres, GlobalSurg, the Dutch DCCG and the JCOG surgical groups show that surgeons will randomise when infrastructure exists; the network makes this permanent and international, with priority to questions where practice varies most.","asOf":"2026-09-08","links":[{"label":"GlobalSurg Collaborative","url":"https://globalsurg.org/"},{"label":"IDEAL Collaboration","url":"https://www.ideal-collaboration.net/"}],"tags":[],"related":["idea-fund-non-drug-trial-quota","idea-fund-surgical-video-registry","idea-fund-organ-preservation-programme"],"cancers":[],"sections":[],"technologies":["robotic-surgery","sentinel-node"],"targets":[],"drugs":[],"companies":["jcog","alliance-oncology"],"institutions":["royal-marsden","ncc-japan"],"pathways":[],"terms":[],"trials":[],"people":["kitagawa-yuko","sano-takeshi","chaturvedi-pankaj"],"bottlenecks":["b-surgery-radiation-innovation","b-trial-enrolment"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A funded network completes at least ten adequately powered randomised surgical trials per five years with more than 80% accrual to target, compared with the current pattern of frequent under-accrual, and at least half change guideline recommendations.","rationale":"Where surgical trial infrastructure has been funded, landmark results followed: the LACC trial on minimally invasive radical hysterectomy, the JCOG gastric lymphadenectomy trials, the Dutch TME trial, and the CLASS and COLOR laparoscopic colectomy trials all changed practice worldwide. The scarcity is of infrastructure and funding, not of questions or willing surgeons.","test":"Fund the network for one five-year cycle with a portfolio of five trials and audit accrual, completion and guideline impact against surgical trials run without network support in the same period.","maturity":"early-clinical","actor":"policy","cost":"large","horizonYears":5},{"id":"idea-tr2-perpetual-platforms","kind":"idea","name":"A perpetual platform trial in every major cancer, funded as infrastructure","aka":[],"tldr":"Instead of starting a new trial for every drug pair, keep one always-open trial per cancer that new arms can join and leave, sharing the same control group.","summary":"STAMPEDE (prostate) and I-SPY 2 (breast) showed that a standing master protocol with a shared control arm can test a succession of treatments for a fraction of the cost and time of separate trials. Yet most common cancers still have no perpetual platform. The proposal is a ten-year, ring-fenced infrastructure grant per tumour type (lung, colorectal, pancreas, ovary, bladder, glioma, myeloma and others) so that the platform outlives any single sponsor or investigator.","asOf":"2026-09-08","links":[{"label":"STAMPEDE trial","url":"http://www.stampedetrial.org/"},{"label":"I-SPY trials","url":"https://www.ispytrials.org/"}],"tags":[],"related":["cruk","nci"],"cancers":["pancreatic","glioblastoma","ovarian","urothelial"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["basket-umbrella-platform"],"trials":["stampede"],"people":[],"bottlenecks":["b-combination-space","b-trial-design"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Cancers with a funded perpetual platform will evaluate at least three times as many combination arms per year, at less than half the per-arm cost, compared with matched cancers relying on stand-alone trials, within five years of funding.","rationale":"STAMPEDE randomised over 10,000 men across ten arms with a single control population and changed standard of care three times. Shared controls, standing ethics approval and pre-built data pipelines remove the fixed costs that make combination trials slow.","test":"Fund platforms in two cancers without one (for example pancreas and glioma) and compare arms opened, accrual rate and cost per randomised patient against the two prior years of conventional trials in the same disease.","maturity":"being-tested-at-scale","actor":"philanthropy","cost":"large","horizonYears":5},{"id":"idea-fund-phase-zero-fund","kind":"idea","name":"A phase 0 fund to test academic compounds in humans with microdoses and imaging","aka":[],"tldr":"Before investing in a full trial, give a few patients a tiny dose of a new compound and use scans and blood tests to see whether it reaches the tumour and hits its target. Fund these small studies as a matter of routine.","summary":"Phase 0 (exploratory IND) studies use microdoses or short courses to measure pharmacokinetics, target engagement (via PET tracers, tumour biopsies or pharmacodynamic markers) and biodistribution before committing to IND-enabling toxicology at full scale. They are cheap, fast and answer the question that kills most academic compounds late: does it get where it needs to go and do what it should in people? A dedicated fund pays for radiolabelling, tracer synthesis, phase 0 unit costs and biopsy-based pharmacodynamics for academic assets, with a rule that assets failing target engagement are dropped and published.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The valley of death between lab and product): Butler, Translational research: crossing the valley of death (Nature 2008)","url":"https://doi.org/10.1038/453840a"}],"tags":[],"related":["idea-fund-ind-enabling-fund","idea-fund-fast-grants-oncology","idea-fund-academic-radiopharma-pipeline"],"cancers":[],"sections":[],"technologies":["immuno-pet","pet","liquid-biopsy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["suv"],"trials":[],"people":[],"bottlenecks":["b-translational-valley","b-preclinical-models"],"keyPapers":["paper-butler-nature"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Routing academic candidates through funded phase 0 studies kills at least 30% before IND-enabling investment and raises the phase 2 success rate of those that proceed compared with the historical academic pipeline, at a cost per candidate under $1 million.","rationale":"Regulatory frameworks for exploratory INDs exist in the US and EU; the NCI ran a phase 0 programme demonstrating feasibility with a PARP inhibitor. Immuno-PET and radiolabelled small molecules now allow direct measurement of tumour delivery for many modalities, including antibodies and ADCs.","test":"Fund phase 0 studies for ten academic assets and compare downstream attrition and cost with a matched historical cohort that went straight to IND-enabling work.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":2},{"id":"idea-data-patient-explainers-per-recommendation","kind":"idea","name":"A plain-language explainer for every guideline recommendation, in every major language","aka":[],"tldr":"For each treatment recommendation in the guidelines, publish a short explanation patients can read in their own language: what it is, why it is recommended, and what the evidence says.","summary":"Patient information is written separately from guidelines and lags them. The proposal generates and expert-verifies a patient explainer for each recommendation in a computable guideline (using the structured evidence and plain-language summaries), checked for reading age, translated into at least 20 languages, and updated automatically when the recommendation changes. ESMO patient guides and NCCN patient guidelines are precedents but are updated slowly.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Knowledge reaches practice too slowly): Morris, Wooding & Grant, The answer is 17 years, what is the question (JRSM 2011)","url":"https://doi.org/10.1258/jrsm.2011.110180"}],"tags":[],"related":["cancer-gov-pdq","idea-data-computable-living-guidelines"],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-knowledge-diffusion","b-misinformation","b-patient-voice"],"keyPapers":["paper-morris-j-r-soc-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Patients given recommendation-level explainers will report higher understanding and shared decision-making scores, and will be less likely to follow misinformation, than those receiving general information leaflets.","rationale":"Decision aids improve knowledge and reduce decisional conflict in randomised trials; tying them to the live guideline solves the currency problem that plagues static leaflets.","test":"Randomise patients at decision points in two cancers to explainers versus standard leaflets; measure knowledge, decisional conflict and use of unproven treatments.","maturity":"speculative","actor":"patients","cost":"small","horizonYears":2},{"id":"idea-data-plain-language-summary-mandate","kind":"idea","name":"A plain-language summary of every cancer trial result within a year","aka":[],"tldr":"Every cancer trial would have to publish a short, clear summary that patients can understand, within twelve months of results, in one public place.","summary":"The EU Clinical Trials Regulation requires lay summaries within 12 months of trial end, but compliance is incomplete, quality varies and there is no US equivalent. The proposal is a global requirement (via ICMJE, registries and funders) that every interventional oncology trial deposit a plain-language summary meeting a readability standard, machine-tagged to the trial record, translated into major languages, and hosted centrally with the structured results.","asOf":"2026-09-08","links":[{"label":"EU CTR lay summary guidance","url":"https://health.ec.europa.eu/medicinal-products/clinical-trials/clinical-trials-regulation-eu-no-5362014_en"}],"tags":[],"related":["clinicaltrials-gov","eudract-ctis"],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-knowledge-diffusion","b-patient-voice","b-misinformation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Universal plain-language summaries will raise patient awareness of trial results and be used by more than a quarter of patients making treatment decisions in surveyed populations within five years.","rationale":"Patients report that they cannot find or understand trial results; the EU regulation shows the requirement is enforceable, and structured hosting makes summaries discoverable.","test":"Audit compliance and readability of EU lay summaries in oncology; pilot central hosting and translation for one year and measure access and patient-reported use.","maturity":"being-tested-at-scale","actor":"regulator","cost":"small","horizonYears":2},{"id":"idea-acc-metronomic-lmic-platform-trial","kind":"idea","name":"A platform trial of very-low-cost metronomic chemotherapy in LMIC common cancers","aka":[],"tldr":"Frequent tiny doses of cheap old chemotherapy pills have shown surprising benefit in some cancers. A single large trial network in India and Africa could find out where this works and where it does not.","summary":"Metronomic regimens (low-dose oral methotrexate, cyclophosphamide, celecoxib) cost a few dollars a month and need no infusion. Tata Memorial trials showed a survival benefit for metronomic maintenance in head and neck cancer, but evidence in other tumours is thin and mostly single-centre. A multi-country platform trial with a shared control arm, adding and dropping regimens and tumour types, would generate definitive answers and could be run largely by nurses.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Most of the world has almost no cancer care): WHO fact sheet, Cancer","url":"https://www.who.int/news-room/fact-sheets/detail/cancer"}],"tags":[],"related":[],"cancers":["head-and-neck","cervical","tnbc"],"sections":[],"technologies":["cytotoxic-chemotherapy"],"targets":[],"drugs":[],"companies":[],"institutions":["tata-memorial"],"pathways":[],"terms":["basket-umbrella-platform"],"trials":[],"people":[],"bottlenecks":["b-global-access","b-generic-repurposing","b-trial-design"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"In at least two of five common LMIC tumour types, a metronomic regimen will improve overall survival over best supportive care or standard palliative chemotherapy at less than 5% of the drug cost.","rationale":"Head-and-neck results and the biology of anti-angiogenic and immunomodulatory low-dose schedules give a plausible mechanism; the drugs are on every essential medicines list.","test":"Run a phase 3 platform across the National Cancer Grid and African partner sites with overall survival and quality of life as endpoints, with pre-specified futility stopping per arm.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":5},{"id":"idea-fund-intraoperative-imaging-trials","kind":"idea","name":"A pragmatic trial network for intraoperative margin tools, paid on margin reduction","aka":[],"tldr":"Tools that show surgeons where the tumour ends during the operation could cut the number of patients who need a second operation, but none has been properly tested at scale. A network would run those trials and pay on results.","summary":"A standing network of surgical centres running randomised, pragmatic trials of fluorescence-guided surgery agents, intraoperative specimen imaging, optical and mass-spectrometry margin probes and AI-based margin prediction, with positive-margin and re-operation rates as primary endpoints and payer contracts that reimburse devices on demonstrated margin reduction. Several agents and devices are approved or near approval, but adoption is slow because evidence is single-centre and payers are unconvinced. The network would also standardise pathology margin assessment, which varies enough to confound trials.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Surgery and radiotherapy cure most, get least): Sullivan et al., Global cancer surgery (Lancet Oncology Commission 2015)","url":"https://doi.org/10.1016/S1470-2045(15)00223-5"}],"tags":[],"related":["idea-fund-device-and-technique-translation-fund","idea-fund-surgical-trials-network"],"cancers":["breast-hr-positive","head-and-neck","prostate"],"sections":[],"technologies":["fluorescence-guided-surgery","optical-imaging"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-surgery-radiation-innovation","b-translational-valley"],"keyPapers":["paper-sullivan-lancet-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"The network completes randomised trials of at least five intraoperative margin technologies within four years, at least two of which reduce positive margins or re-operation by a third in breast, head and neck or prostate surgery and are adopted under outcome-based payment.","rationale":"Re-operation rates after breast-conserving surgery run at a fifth in many systems; positive margins predict recurrence in most solid tumours. Pegulicianine and other agents have shown margin detection in trials, but comparative evidence across technologies and payment models is absent.","test":"Launch two randomised trials in breast and head and neck surgery with margin primary endpoints and a pilot outcome-based payment contract with one payer.","maturity":"early-clinical","actor":"clinic","cost":"medium","horizonYears":4},{"id":"idea-reg-statin-hcc-prevention-trial","kind":"idea","name":"A pragmatic trial of statins to prevent liver cancer in people with cirrhosis","aka":[],"tldr":"People with cirrhosis have a high risk of liver cancer, and those who happen to take statins seem to get it less often. A proper trial would settle whether statins should be prescribed for prevention.","summary":"Large observational studies and meta-analyses associate statin use with substantially lower hepatocellular carcinoma incidence in cirrhosis and chronic hepatitis, with plausible mechanisms (reduced portal pressure, anti-fibrotic and anti-proliferative effects), and small randomised trials of simvastatin in cirrhosis show improved portal haemodynamics. No adequately powered prevention trial with cancer incidence as the endpoint has been completed. The proposal is a pragmatic randomised trial of atorvastatin or simvastatin versus placebo in compensated cirrhosis with HCC incidence as the primary outcome, run through hepatology networks and registries.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (No incentive to repurpose cheap drugs): Pantziarka et al., The Repurposing Drugs in Oncology (ReDO) Project (ecancer 2014)","url":"https://doi.org/10.3332/ecancer.2014.442"}],"tags":[],"related":[],"cancers":["hcc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-generic-repurposing","b-prevention-adoption"],"keyPapers":["paper-pantziarka-ecancermedicalscience"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Statin therapy reduces the 5-year incidence of hepatocellular carcinoma in compensated cirrhosis by at least 30% relative to placebo.","rationale":"Cirrhosis is one of the few settings where a very high-risk population is already under surveillance, making a prevention trial feasible with a few thousand patients; the drug is safe, cheap and already indicated in many of these patients for cardiovascular reasons.","test":"Randomised placebo-controlled trial of about 3,000 patients with compensated cirrhosis followed for five years with ultrasound surveillance; HCC incidence primary endpoint.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":7},{"id":"idea-data-precompetitive-cancer-foundation-model","kind":"idea","name":"A pre-competitive consortium to train a shared multimodal cancer foundation model","aka":[],"tldr":"Companies, hospitals and funders would form a consortium, like the Structural Genomics Consortium or IMI, to train one multimodal AI on scans, slides, genomes and outcomes from millions of patients by federated training across dozens of health systems, with the data never leaving the hospitals. Members would share the base model and compete on applications built on it.","summary":"The existing idea of patient-level multimodal foundation models for treatment selection depends on data no single organisation holds. The proposal is the governance and infrastructure to build one as shared infrastructure: a consortium (like the Structural Genomics Consortium or IMI) with federated training across dozens of health systems, pre-agreed data-use terms, open or consortium-licensed weights, a neutral host, and evaluation on sequestered prospective data. Members compete on applications built on top, not on the base model.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (AI that is built but not validated or deployed): Wu et al., How medical AI devices are evaluated: limitations and recommendations from an analysis of FDA approvals (Nature Medicine 2021)","url":"https://doi.org/10.1038/s41591-021-01312-x"}],"tags":[],"related":["idea-multimodal-foundation-model","idea-data-federated-learning-imaging"],"cancers":[],"sections":["ai-computation"],"technologies":["pathology-foundation-model","digital-pathology-ai"],"targets":[],"drugs":[],"companies":["owkin","tempus","paige","pathai"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-ai-validation","b-data-silos","b-ip-collaboration"],"keyPapers":["paper-wu-nat-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A consortium-trained multimodal model on data from more than a million patients will outperform any single-organisation model on held-out prospective prediction tasks, and shared access will produce more validated clinical applications within five years than proprietary efforts.","rationale":"Pre-competitive consortia have worked in genomics (SNP Consortium), structural biology and drug safety; the base-model layer is the natural pre-competitive layer for cancer AI because its value grows with data no one company can assemble.","test":"Convene ten health systems and five companies; train a first model on two modalities federatedly; benchmark against members' internal models on sequestered data; publish.","maturity":"speculative","actor":"industry","cost":"large","horizonYears":5},{"id":"idea-fund-target-validation-consortium","kind":"idea","name":"A pre-competitive consortium to validate or kill academic targets before licensing","aka":[],"tldr":"Companies and public funders would jointly pay for standardised experiments that confirm or refute new cancer targets, sharing all results openly, so nobody wastes years on a target that does not hold up.","summary":"A consortium modelled on the NIH Accelerating Medicines Partnership and Open Targets in which companies, funders and academic centres pool money to run standardised, blinded target validation (genetic dependency across large cell panels, in vivo knock-out in relevant models, human genetic and expression evidence, tool-compound pharmacology) on nominated academic oncology targets, with all data released publicly. Companies then compete downstream on chemistry and biology. This raises the quality of what enters the valley and removes duplicated validation efforts inside every company.","asOf":"2026-09-08","links":[{"label":"Accelerating Medicines Partnership","url":"https://www.nih.gov/research-training/accelerating-medicines-partnership-amp"},{"label":"Open Targets","url":"https://www.opentargets.org/"}],"tags":[],"related":["depmap","open-targets","idea-fund-precompetitive-undruggable-consortium","idea-fund-replication-set-aside"],"cancers":[],"sections":[],"technologies":["crispr-screens","pdx-models"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-translational-valley","b-reproducibility","b-ip-collaboration"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Targets that pass consortium validation progress to lead optimisation at twice the rate of unvalidated academic targets, and published consortium negative results reduce industry programmes started on refuted targets within two years of release.","rationale":"AMP has produced widely used open datasets in Alzheimer's disease and type 2 diabetes and is credited with shifting industry target choice; Open Targets and DepMap are already the first stop for oncology target triage. The remaining gap is standardised in vivo validation with open release.","test":"Pilot with five companies and two funders on twenty nominated targets; release results and track downstream programme starts and licensing of validated versus refuted targets over three years.","maturity":"early-clinical","actor":"industry","cost":"medium","horizonYears":4},{"id":"idea-data-target-trial-emulation-standard","kind":"idea","name":"A pre-registered standard for emulating trials with real-world data","aka":[],"tldr":"When researchers use hospital records to ask 'would drug A have beaten drug B in a trial', they should follow a published recipe and register their plan first, so the answer can be trusted.","summary":"Target trial emulation (specifying the hypothetical randomised trial, then mimicking it in observational data) is the accepted framework for causal inference from real-world data, but the rigour of oncology emulations is inconsistent. The proposal is a formal standard: a protocol template (eligibility, treatment strategies, assignment, time zero, outcomes, causal contrast, analysis plan), mandatory pre-registration, and a requirement to report a positive control emulation of a known RCT in the same dataset, adopted by regulators and journals as a condition of considering RWE.","asOf":"2026-09-08","links":[{"label":"RCT-DUPLICATE","url":"https://www.rctduplicate.org/"}],"tags":[],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["real-world-evidence","hazard-ratio"],"trials":[],"people":[],"bottlenecks":["b-real-world-evidence","b-trial-design"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Emulations that follow the standard and pass a positive-control calibration will agree with subsequent randomised trials on the direction of effect in more than 85 percent of cases, versus roughly 60 percent for unstandardised observational oncology studies.","rationale":"The RCT-DUPLICATE project showed that carefully designed emulations can reproduce RCT results when design elements are matched; the failures came from avoidable design flaws such as immortal time bias. A standard forces the fixes.","test":"Apply the standard prospectively to ten oncology questions with ongoing RCTs; lock the emulation results before the trials read out; compare.","maturity":"early-clinical","actor":"regulator","cost":"small","horizonYears":3},{"id":"idea-bio1-undruggable-open-consortium","kind":"idea","name":"A precompetitive consortium for the twenty hardest cancer targets","aka":[],"tldr":"No single company will spend a decade on a target that might be impossible. A shared, openly published effort across the twenty hardest targets spreads that risk.","summary":"The Structural Genomics Consortium showed that open chemical probes, published without patent restrictions, accelerate whole fields. The proposal is an oncology equivalent focused on the undruggable list (MYC, mutant p53, non-G12C RAS, fusion transcription factors, phosphatases), with pooled funding from several companies and funders, mandatory open data, milestone-based go/no-go, and freedom to operate for downstream drug development.","asOf":"2026-09-08","links":[{"label":"Structural Genomics Consortium","url":"https://www.thesgc.org/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["icr-london","broad-institute","cruk"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-undruggable-targets","b-ip-collaboration","b-funding-allocation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A ten-year consortium produces validated chemical probes for at least five of twenty designated undruggable targets, and probe availability measurably increases the number of independent publications and programmes on those targets.","rationale":"The economics of individually funded undruggable programmes are unattractive because failure is likely and the science is generalisable; pooling makes the expected value positive for each contributor.","test":"A five-year pilot with three targets and four funders, benchmarked against matched targets developed conventionally on probe delivery, publication count and downstream programme starts.","maturity":"speculative","actor":"philanthropy","cost":"large","horizonYears":10},{"id":"idea-moon-neuropathy-prevention-programme","kind":"idea","name":"A prevention programme for chemotherapy nerve damage: SARM1 inhibitors, cooling and compression","aka":[],"tldr":"Nerve damage from taxanes and platinum is common, often permanent and has no approved preventive. Test the most promising candidates head to head in one programme.","summary":"Chemotherapy-induced peripheral neuropathy affects a large share of patients treated with taxanes, platinum or bortezomib and drives dose reduction. SARM1, an executioner of axon degeneration, is validated genetically in mouse models and inhibitors are in early clinical development for other neuropathies; HDAC6 inhibitors and cryotherapy or compression of hands and feet have supportive data. The proposal is a multi-arm platform trial in adjuvant breast and colorectal cancer comparing candidate preventives against placebo with a patient-reported neuropathy endpoint (EORTC CIPN20) and quantitative sensory testing.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Toxicity and quality of life are undervalued): Di Maio et al., Symptomatic toxicities experienced during anticancer treatment: agreement between patient and physician reporting (JCO 2015)","url":"https://doi.org/10.1200/JCO.2014.57.9334"}],"tags":[],"related":[],"cancers":["breast-hr-positive","colorectal","multiple-myeloma"],"sections":[],"technologies":["cytotoxic-chemotherapy","platinum"],"targets":[],"drugs":["paclitaxel"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol"],"keyPapers":["paper-di-maio-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"At least one intervention reduces moderate-to-severe patient-reported neuropathy at 12 months by an absolute 15 percentage points without compromising chemotherapy dose delivery or disease-free survival.","rationale":"Axon degeneration has defined molecular executioners; cooling has already shown signals; the population is large and homogeneous, making trials fast and cheap relative to oncology drugs.","test":"Phase 2/3 platform trial in adjuvant taxane and oxaliplatin regimens with pre-specified futility and dose-delivery safety monitoring.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":5},{"id":"idea-data-standard-of-care-api","kind":"idea","name":"A public API serving the current standard of care for any cancer, stage and biomarker","aka":[],"tldr":"A free web service where any app or hospital system can ask 'what is the recommended treatment for this exact situation today' and get a cited, versioned answer.","summary":"Developers of patient apps, trial-matching tools and decision support each hand-encode standards of care and let them rot. A public API over the computable guidelines and evidence graph, returning current recommendations with evidence grades, citations and version identifiers for a structured query (cancer, stage, biomarkers, line), would make currency a solved problem for the ecosystem, in the way that drug-interaction databases became shared infrastructure.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Knowledge reaches practice too slowly): Morris, Wooding & Grant, The answer is 17 years, what is the question (JRSM 2011)","url":"https://doi.org/10.1258/jrsm.2011.110180"}],"tags":[],"related":["idea-data-computable-living-guidelines","idea-data-open-evidence-knowledge-graph"],"cancers":[],"sections":["ai-computation"],"technologies":["ai-trial-matching"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-knowledge-diffusion","b-ai-validation"],"keyPapers":["paper-morris-j-r-soc-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Within three years, the majority of new oncology software products will consume the API rather than hand-encode standards, and the currency of recommendations in those products will match the guidelines within days.","rationale":"Shared infrastructure APIs (maps, payments, drug databases) are consumed universally once reliable; oncology standards of care are a natural candidate and have never been offered this way.","test":"Publish the API for two diseases; count integrations and measure the recommendation currency of consuming products versus non-consuming products after one year.","maturity":"speculative","actor":"engineering","cost":"medium","horizonYears":2},{"id":"idea-tr2-organoid-matrix-atlas","kind":"idea","name":"A public atlas of drug-pair responses across a thousand patient-derived organoids","aka":[],"tldr":"Build a large, openly shared dataset of how tumour organoids respond to drug pairs, so that anyone can look up which combinations might work for which tumour type.","summary":"Existing combination screens use cell lines (NCI ALMANAC, AZ-DREAM). Organoids preserve more of the patient's tumour biology but no large public pairwise dataset exists. A consortium screening 1,000 characterised organoids (with genomics, transcriptomics and, where available, donor outcome) against a matrix of 100 approved and late-stage drugs would be the training set for every in silico combination model.","asOf":"2026-09-08","links":[{"label":"Cancer Models (HCMI)","url":"https://www.cancer.gov/ccg/research/functional-genomics/hcmi"}],"tags":[],"related":["cancer-models","depmap","idea-tr2-synergy-ranking-engine"],"cancers":[],"sections":[],"technologies":["organoids","functional-drug-testing","wes-wgs"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-combination-space","b-preclinical-models","b-data-silos"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Models trained on the atlas will predict clinical combination outcomes (randomised phase 2 success) with better calibration than models trained on cell-line matrices alone, measured against the next fifty combination readouts.","rationale":"Data scale drove progress in every predictive field. The Human Cancer Models Initiative built the organoids; nobody has systematically screened them in combination.","test":"Screen the first 200 organoids across 50 drugs in full pairwise matrices, release the data, and run an open prediction challenge scored on held-out organoids and on existing clinical combination results.","maturity":"preclinical-evidence","actor":"philanthropy","cost":"large","horizonYears":4},{"id":"idea-moon-ai-cancer-answer-audit","kind":"idea","name":"A public benchmark and audit of chatbot answers to cancer questions","aka":[],"tldr":"Patients now ask AI assistants about their cancer. Test those assistants regularly on real questions, publish the scores, and certify the ones that meet the bar.","summary":"Large language models are becoming a primary source of medical information; studies show variable accuracy, occasional dangerous advice and inconsistent sourcing on oncology questions. The proposal is an independent, continuously updated benchmark of patient-style cancer questions (treatment options, side-effects, alternative therapies, prognosis) scored by oncologists and patients for accuracy, safety, sourcing and readability, with public leaderboards and a certification mark for assistants that meet thresholds and disclose limitations.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Misinformation and unproven therapies): Johnson et al., Cancer misinformation and harmful information on Facebook and other social media (JNCI 2022)","url":"https://doi.org/10.1093/jnci/djab141"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-misinformation","b-ai-validation"],"keyPapers":["paper-johnson-j-natl-cancer-inst"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Public auditing raises the accuracy and safety of assistant answers to cancer questions across vendors within a year, and certified assistants are preferred by patient organisations.","rationale":"Benchmarks drive model behaviour in AI development; making the oncology benchmark public and patient-facing turns that pressure toward safety.","test":"Run the benchmark quarterly on major assistants for a year; measure score trajectories and adoption of the certification by patient organisations and health systems.","maturity":"early-clinical","actor":"data","cost":"small","horizonYears":1},{"id":"idea-moon-biomarker-validation-utility","kind":"idea","name":"A public biomarker validation utility with pre-diagnostic biobanks and blinded testing","aka":[],"tldr":"Thousands of cancer biomarkers are published; almost none reach patients because nobody validates them fairly. Create a public service that tests any candidate blind against stored samples.","summary":"Biomarker failure stems from small discovery sets, spectrum bias and absence of blinded validation on prospectively collected samples. Cohorts with pre-diagnostic samples (UK Biobank, PLCO, national screening biobanks) and trial biorepositories exist but access is slow and fragmented. The proposal is a funded utility: a governed catalogue of pre-diagnostic and trial samples with outcomes, a standard blinded validation protocol (PRoBE design), rapid access for academic and commercial developers at cost, and public reporting of all results including failures.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Biomarkers are not validated or standardised): Fernandez et al., Examination of low ERBB2 protein expression in breast cancer tissue (JAMA Oncology 2022)","url":"https://doi.org/10.1001/jamaoncol.2021.7239"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["liquid-biopsy","proteomics"],"targets":[],"drugs":[],"companies":[],"institutions":["nci"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-biomarker-validation","b-reproducibility"],"keyPapers":["paper-fernandez-jama-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"The utility validates or refutes at least 100 candidate biomarkers in five years, and biomarkers passing it show performance in clinical use within a third of the historical time and with markedly less performance decay.","rationale":"Early Detection Research Network experience shows blinded validation kills most candidates quickly and cheaply; a shared utility makes that the default rather than the exception.","test":"Fund the utility and run the first 20 blinded validations; measure throughput, time to result, and concordance of validated performance with later clinical performance.","maturity":"early-clinical","actor":"data","cost":"large","horizonYears":5},{"id":"idea-fund-dollars-per-death-dashboard","kind":"idea","name":"A public dashboard of research money per death for every cancer","aka":[],"tldr":"A simple website that shows, every year, how much research money each cancer receives compared with how many people it kills, so the gaps are impossible to ignore.","summary":"Combine machine-readable grant data (NIH RePORTER, the International Cancer Research Partnership, UKRI Gateway to Research, EU CORDIS, and charity annual reports) with mortality and DALY data to publish research dollars per death, per DALY and per incident case, by cancer type and by Common Scientific Outline category (biology, prevention, detection, treatment, survivorship). Include a trend line and a 'what would burden-weighted look like' comparison. Cheap, because most of the data are already public; the value is the persistent, cited visibility.","asOf":"2026-09-08","links":[{"label":"NIH RePORTER","url":"https://reporter.nih.gov/"},{"label":"International Cancer Research Partnership","url":"https://www.icrpartnership.org/"}],"tags":[],"related":["globocan","seer","idea-fund-burden-weighted-portfolio","idea-fund-white-space-map"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-funding-allocation","b-knowledge-diffusion"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Annual publication of a widely-cited dollars-per-death ranking shifts relative funding: within five years the coefficient of variation of spend per death across the 15 most common cancers falls measurably, and funders cite the dashboard in strategy documents.","rationale":"League tables change behaviour when they are public and persistent: hospital mortality reporting, university rankings and the Access to Medicine Index all altered institutional priorities. Cancer-specific funding gap analyses appear as one-off papers and are forgotten; a living dashboard is not.","test":"Build the dashboard from public sources in under a year; measure media citations, funder strategy citations and changes in spend allocation over three cycles against a pre-registered prediction of no change.","maturity":"speculative","actor":"data","cost":"small","horizonYears":1},{"id":"idea-tr1-site-equity-index","kind":"idea","name":"A public equity index for trial sites and sponsors, tied to funding","aka":[],"tldr":"Rank hospitals and companies each year on how well their trial participants match the people with the disease in their area, and use the ranking when deciding who gets public research money and trial contracts.","summary":"An independent body computes, for each site and sponsor, participation-to-prevalence ratios by race, ethnicity, age, sex and rurality across their oncology trials, publishes the index annually, and public funders and cooperative groups weight site selection and grant scoring by it. Sponsors use it in site selection.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Trials do not represent the people who get cancer): Loree et al., Disparity of race reporting and representation in trials leading to cancer drug approvals (JAMA Oncology 2019)","url":"https://doi.org/10.1001/jamaoncol.2019.1870"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["nci","asco"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-diversity","b-incentive-misalignment"],"keyPapers":["paper-loree-jama-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Public ranking with funding consequences will raise representativeness at low-ranked sites more than internal reporting does, by making equity a competitive metric.","rationale":"Public quality rankings changed hospital behaviour in surgery and infection control; trial equity currently has no comparable visible metric.","test":"Publish the index for two years; compare change in representativeness between sites in the bottom quartile and those above.","maturity":"speculative","actor":"policy","cost":"small","horizonYears":2},{"id":"idea-moon-generics-for-cancer-fund","kind":"idea","name":"A public fund and label pathway to trial generic drugs against cancer","aka":[],"tldr":"Cheap old drugs such as aspirin, statins, metformin and beta-blockers show hints of cancer benefit but no company will pay for the trials. Create a public fund and a way to update their labels.","summary":"Repurposing candidates with plausible mechanisms and observational signals rarely reach definitive trials because generic status removes the commercial incentive; the aspirin adjuvant trials (ADD-ASPIRIN) are a rare exception. The proposal is a dedicated public fund for pragmatic, registry-embedded randomised trials of generics in defined cancer indications, coupled with a regulatory pathway allowing third parties (academic groups, health systems) to obtain label updates, and payer commitments to reimburse on positive results.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (No incentive to repurpose cheap drugs): Pantziarka et al., The Repurposing Drugs in Oncology (ReDO) Project (ecancer 2014)","url":"https://doi.org/10.3332/ecancer.2014.442"}],"tags":[],"related":[],"cancers":["colorectal","breast-hr-positive","prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["cruk"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-generic-repurposing","b-incentive-misalignment"],"keyPapers":["paper-pantziarka-ecancermedicalscience"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"The fund completes at least ten definitive repurposing trials in a decade and delivers at least two new indications with population-level mortality impact at negligible drug cost.","rationale":"The candidate list is long, the drugs are safe and cheap, and pragmatic trial designs make each question affordable; the missing element is an owner with an incentive.","test":"Fund five trials in the first tranche (for example beta-blockers in early breast cancer, statins in high-risk prostate cancer, metformin in specific contexts) with pre-registered designs and registry follow-up.","maturity":"early-clinical","actor":"policy","cost":"large","horizonYears":6},{"id":"idea-tr1-public-de-escalation-trial-fund","kind":"idea","name":"A public fund for trials that test less treatment","aka":[],"tldr":"No company will pay to find out whether six months of its drug works as well as twelve. A dedicated public fund would pay for those trials, which save patients side effects and health systems money.","summary":"A ring-fenced fund (national research agency or philanthropic) that only supports randomised non-inferiority trials of shorter duration, lower dose, fewer cycles, omitted components or less frequent dosing of approved therapies, with a standing statistical and design core and pre-agreed non-inferiority margins co-developed with patients. Precedents: PERSEPHONE (6 vs 12 months trastuzumab), SOLD, and low-dose abiraterone; funders such as the UK NIHR HTA programme and the Anticancer Fund have supported some.","asOf":"2026-09-08","links":[{"label":"The Anticancer Fund","url":"https://www.anticancerfund.org/"},{"label":"NIHR","url":"https://www.nihr.ac.uk/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":["trastuzumab","pembrolizumab"],"companies":[],"institutions":["cruk"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-design","b-toxicity-qol","b-incentive-misalignment"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Each dollar invested in de-escalation trials will return multiples in avoided treatment cost within five years of read-out, and at least a third of funded trials will change guidelines.","rationale":"The incentive gap is structural: de-escalation reduces revenue. The trials are cheap relative to the drug spend they interrogate, and several have already changed practice.","test":"Fund ten trials over five years and audit guideline changes, avoided drug costs and patient-reported toxicity differences against the fund's outlay.","maturity":"being-tested-at-scale","actor":"philanthropy","cost":"large","horizonYears":5},{"id":"idea-reg-global-repurposing-fund","kind":"idea","name":"A public fund that pays for phase 3 trials of cheap, off-patent drugs against cancer","aka":[],"tldr":"Old drugs like aspirin, statins and beta-blockers show hints of fighting cancer, but no company will pay to prove it. A dedicated public fund should.","summary":"The ReDO project (Anticancer Fund) catalogues hundreds of off-patent drugs with anticancer signals; almost none have reached a definitive trial. Public funders have run a few (Add-Aspirin, ALASCCA, MA.32 metformin), and the UK, Belgium and the EU have discussed repurposing frameworks. The proposal is a dedicated international fund (order of $200-300 million a year, from NIHR, NCI, EU and philanthropy) with an independent prioritisation panel, a standing trial network, and a requirement that funded trials be designed to support regulatory label updates and guideline inclusion.","asOf":"2026-09-08","links":[{"label":"Anticancer Fund ReDO project (page moved; nearest live section)","url":"https://www.anticancerfund.org/en/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-generic-repurposing","b-funding-allocation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"The fund completes at least ten definitive repurposing trials in its first decade, of which at least two produce practice-changing survival benefits at a cost per life-year gained under $5,000.","rationale":"Repurposed generics have no sponsor because the returns cannot be captured; the expected value to health systems is enormous even at a low hit rate because the drugs cost almost nothing to deliver once proven.","test":"Capitalise the fund, select the first five trials through open prioritisation, and report time to enrolment, cost per trial and results against a pre-registered portfolio plan.","maturity":"early-clinical","actor":"philanthropy","cost":"large","horizonYears":6},{"id":"idea-fund-academic-sponsor-indemnity-pool","kind":"idea","name":"A public indemnity pool so universities can sponsor first-in-human cancer trials","aka":[],"tldr":"Universities often refuse to be the legal sponsor of a first-in-human trial because they cannot afford the insurance and liability. A shared public insurance pool would remove that block.","summary":"A government- or funder-backed indemnity and insurance pool that covers no-fault compensation and sponsor liability for academic and non-profit sponsored early-phase oncology trials meeting defined quality standards (independent scientific review, GMP product, approved protocol), priced at cost and open to any accredited institution. Sponsor liability and insurance premiums are a frequently cited reason academic legal offices decline to sponsor first-in-human trials of academic products, especially cell and gene therapies, pushing teams to license early on poor terms or to abandon assets. Several countries operate national no-fault schemes for trial injury; extending them to cover sponsor indemnity for academic early-phase trials is a small, cheap change with a large unblocking effect.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The valley of death between lab and product): Butler, Translational research: crossing the valley of death (Nature 2008)","url":"https://doi.org/10.1038/453840a"}],"tags":[],"related":["idea-fund-global-academic-phase-one-network","idea-fund-public-nonprofit-cro","idea-fund-hospital-exemption-registry"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-translational-valley","b-trial-design"],"keyPapers":["paper-butler-nature"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Where a pool exists, the number of academic-sponsored first-in-human oncology trials rises by at least half within three years, and the proportion of academic assets licensed before any human data falls, indicating that institutions retain assets longer and on better terms.","rationale":"Institutions respond to liability exposure: after high-profile gene therapy adverse events, academic sponsorship of first-in-human trials fell sharply where insurance costs rose. Pooling risk across many trials is standard for rare, high-severity events, and the actual claims record of early-phase oncology trials is small relative to premiums charged.","test":"Establish the pool in one country for three years, track academic first-in-human sponsorships, premiums paid and claims, and compare with a neighbouring country without the scheme.","maturity":"speculative","actor":"policy","cost":"medium","horizonYears":2},{"id":"idea-reg-label-divergence-index","kind":"idea","name":"A public index of how the same cancer drug's label differs between countries","aka":[],"tldr":"Nobody keeps track of how differently the same drug is approved and dosed around the world. A public scoreboard would make the differences visible and push regulators to converge.","summary":"For the same oncology drug, the approved indications, biomarker requirements, dosing and line of therapy can differ between FDA, EMA, PMDA, NMPA and others, and the reasons are rarely documented. The proposal is an open, machine-readable dataset that parses approved labels for every oncology drug across at least ten regulators, scores divergence per indication, and publishes the reasons where regulators have stated them. Regulators and sponsors would receive an annual divergence report.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Regulatory divergence between regions): FDA Oncology Center of Excellence, Project Orbis","url":"https://www.fda.gov/about-fda/oncology-center-excellence/project-orbis"}],"tags":[],"related":["fda-approvals"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-regulatory-fragmentation","b-knowledge-diffusion"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Publishing a divergence index is followed within three years by a measurable reduction in the divergence score for new approvals and an increase in the number of harmonising label variations.","rationale":"Measurement changes behaviour; the W.A.I.T. indicator changed the conversation on European access delays. Divergence that is visible must be justified, and much of it has no scientific justification.","test":"Build the index for 50 oncology drugs across ten regulators, publish it, and track divergence scores and harmonising variations annually.","maturity":"speculative","actor":"data","cost":"small","horizonYears":2},{"id":"idea-tr1-trial-desert-map","kind":"idea","name":"A public map of trial deserts to steer where new sites open","aka":[],"tldr":"Combine registry cancer incidence by district with open trial site locations from ClinicalTrials.gov to map the regions where patients live more than an hour from any trial. Sponsors and funders would use it to decide where to open sites and justify site selection in diversity plans.","summary":"An open, regularly updated geospatial dataset joins registry incidence (by county or district) with trial site locations and recruitment status from ClinicalTrials.gov and other registries, producing an index of trial access by disease, with travel-time isochrones and demographic overlays. Sponsors are asked to justify site selection against the map in diversity plans.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Trials do not represent the people who get cancer): Loree et al., Disparity of race reporting and representation in trials leading to cancer drug approvals (JAMA Oncology 2019)","url":"https://doi.org/10.1001/jamaoncol.2019.1870"}],"tags":[],"related":["clinicaltrials-gov","seer","globocan"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["iarc"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-diversity","b-trial-enrolment","b-data-silos"],"keyPapers":["paper-loree-jama-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Regions identified as trial deserts and targeted for new sites will show increased enrolment of rural and minority patients within two years, and site-selection decisions of sponsors using the map will shift toward under-served regions.","rationale":"Site selection is driven by past performance, not by where patients are, reinforcing concentration in the same academic centres. Maps changed resource allocation for pharmacies and emergency services.","test":"Publish the map for the US and one European country; compare geographic distribution of newly opened sites in the following two years with the prior two.","maturity":"speculative","actor":"data","cost":"small","horizonYears":1},{"id":"idea-tr2-reversal-registry","kind":"idea","name":"A public registry of cancer treatments that were later shown not to work","aka":[],"tldr":"Keep a running, well-documented list of cancer practices and approvals that were reversed by later evidence, so the pattern of mistakes is visible and teachable.","summary":"Medical reversals (for example high-dose chemotherapy with stem-cell rescue in breast cancer, several accelerated approvals later withdrawn, bevacizumab in breast cancer) are scattered across the literature. A curated registry with, for each reversal, the original evidence, the reversing trial, the time to reversal, the patients exposed, and the design features that allowed the error would inform regulators and teach trainees.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Failures are hidden): Anderson et al., Compliance with results reporting at ClinicalTrials.gov (NEJM 2015)","url":"https://doi.org/10.1056/NEJMsa1409364"}],"tags":[],"related":["fda-approvals","idea-tr2-failure-taxonomy"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["accelerated-approval"],"trials":[],"people":[],"bottlenecks":["b-negative-results","b-knowledge-diffusion"],"keyPapers":["paper-anderson-n-engl-j-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Analysis of the registry will identify recurring design features (single-arm evidence, surrogate endpoints, small effect sizes) that predict reversal, and regulators will cite these features in subsequent approval decisions.","rationale":"Prasad and colleagues' reviews of reversals in general medicine changed thinking about evidence standards; oncology has enough reversals to learn systematically.","test":"Curate 100 oncology reversals with structured fields; publish the analysis of predictors; monitor citation in regulatory documents.","maturity":"speculative","actor":"data","cost":"small","horizonYears":2},{"id":"idea-data-clinical-ai-model-registry","kind":"idea","name":"A public registry of every AI model used in cancer care","aka":[],"tldr":"Like a trial registry, every AI tool used on real patients would be listed publicly with what it is for, what data it was trained on, how well it performed and which version is running where.","summary":"There is no public record of which AI models are deployed in which hospitals, for what indications, at what versions. The proposal is a mandatory registry (regulator-run or accredited) with a standard model card: intended use, training data summary (sites, years, demographics), validation results by subgroup, version history, deployment sites, and links to post-market performance reports. FDA's list of cleared AI devices is a partial precedent but lacks deployment and performance data.","asOf":"2026-09-08","links":[{"label":"FDA AI-enabled medical devices list","url":"https://www.fda.gov/medical-devices/software-medical-device-samd/artificial-intelligence-enabled-medical-devices"}],"tags":[],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-ai-validation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A public registry will make independent scrutiny possible, reveal the share of deployed models without external validation, and correlate with faster withdrawal of underperforming models.","rationale":"Trial registration transformed accountability in clinical research; AI in care is at the stage trials were before registration, with selective reporting and unknown deployment.","test":"Pilot voluntary registration with 20 hospitals and their vendors for one year; measure completeness and the number of models found to lack external validation; then assess mandatory adoption.","maturity":"speculative","actor":"regulator","cost":"small","horizonYears":2},{"id":"idea-fund-stalled-asset-registry","kind":"idea","name":"A public registry of stalled academic assets and shelved company compounds","aka":[],"tldr":"Thousands of cancer compounds that stopped development for portfolio rather than scientific reasons sit unused in university freezers and company archives. A public catalogue listing each asset's mechanism, stage, data, reason for stopping and licensing contact, with a standard research licence and a brokerage function, would let academic and non-profit developers adopt them.","summary":"A searchable registry where universities and companies list oncology assets that have stopped development (with mechanism, stage reached, available data, reason for stopping and licensing contact), coupled with a standard non-exclusive research licence and a small brokerage function to match assets with academic groups or non-profit developers. NCATS's discontinued assets programme and AstraZeneca's open innovation portal are partial precedents; the National Cancer Institute's NExT programme has taken up some shelved compounds. Most stopped programmes end for portfolio, not scientific, reasons, and their data are otherwise lost.","asOf":"2026-09-08","links":[{"label":"NCI Experimental Therapeutics (NExT) Program","url":"https://next.cancer.gov/"}],"tags":[],"related":["idea-fund-shelved-asset-escrow","idea-fund-nonprofit-pharma","idea-fund-trial-data-trust"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-translational-valley","b-negative-results","b-ip-collaboration"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A registry with standard licences results in at least twenty stalled oncology assets entering new academic or non-profit development within three years, and at least two reaching a new clinical trial.","rationale":"The NCATS pilot with shelved industry compounds led to new indications entering trials within a few years; the constraint was discovery of what existed and negotiation time, both of which a registry with standard terms removes.","test":"Launch with commitments from five companies and ten universities to list assets; count downstream licences and trials over three years.","maturity":"speculative","actor":"data","cost":"small","horizonYears":2},{"id":"idea-data-unanswered-questions-registry","kind":"idea","name":"A public registry of unanswered clinical questions linked to funding calls","aka":[],"tldr":"Keep a public list of the questions doctors and patients most need answered but no trial addresses, and tie research funding to it.","summary":"Guideline panels repeatedly note evidence gaps but the gaps are buried in documents. The James Lind Alliance sets priorities with patients and clinicians but has limited oncology coverage. The proposal creates a structured, open registry of evidence gaps extracted from computable guidelines and living reviews, prioritised by burden and patient input, with funders committing to reference it in calls and trialists to register which gap a trial addresses.","asOf":"2026-09-08","links":[{"label":"James Lind Alliance","url":"https://www.jla.nihr.ac.uk/"}],"tags":[],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["cruk","nci"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-knowledge-diffusion","b-funding-allocation","b-patient-voice"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A gap registry referenced by funders will increase the share of newly funded oncology trials addressing prioritised gaps and reduce redundant trials on already-answered questions.","rationale":"Research waste from redundant and misdirected trials is estimated at a large share of spending; making gaps explicit and prioritised gives funders and trialists a common target.","test":"Extract gaps from ten living reviews; have two funders reference the registry in calls for two years; measure the proportion of funded trials mapping to prioritised gaps versus before.","maturity":"speculative","actor":"philanthropy","cost":"small","horizonYears":2},{"id":"idea-moon-unproven-clinic-registry","kind":"idea","name":"A public registry of unproven cancer clinics and reported outcomes","aka":[],"tldr":"A searchable public record of clinics selling unproven cancer treatments, with the claims they make, the prices, the evidence and the harms reported by patients and doctors.","summary":"Patients spend large sums at clinics offering unproven treatments (high-dose vitamin infusions, unregulated cell therapies, hyperthermia without evidence) and oncologists see the consequences but have nowhere to report them. The proposal is a registry maintained by an independent body, populated by clinician and patient reports and public advertising, with a standard evidence grading and links to regulatory actions, plus a route to notify regulators and platforms.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Misinformation and unproven therapies): Johnson et al., Cancer misinformation and harmful information on Facebook and other social media (JNCI 2022)","url":"https://doi.org/10.1093/jnci/djab141"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["hyperthermia"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["regulatory-agencies"],"trials":[],"people":[],"bottlenecks":["b-misinformation"],"keyPapers":["paper-johnson-j-natl-cancer-inst"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A visible registry reduces spending on listed clinics, increases regulatory enforcement actions, and appears in the top search results for those clinics within a year.","rationale":"Sunlight works where enforcement is slow; consumer protection registries change behaviour in other markets.","test":"Launch with 200 clinics in two countries; measure search visibility, referrals to regulators, and patient-reported awareness in oncology clinics.","maturity":"speculative","actor":"regulator","cost":"small","horizonYears":2},{"id":"idea-tr1-external-control-rulebook","kind":"idea","name":"A public rulebook for when an external or synthetic control arm is acceptable","aka":[],"tldr":"Sometimes a trial cannot randomise, so the new drug is compared with past patients' records. Clear published rules on when that is allowed, and how it must be done, would replace case-by-case guesswork.","summary":"Regulators publish a binding checklist for externally controlled trials: pre-registration of the comparator cohort and analysis before unblinding; target-trial emulation framing; minimum data quality (endpoint ascertainment, line of therapy, index date); quantitative bias analysis and tipping-point reporting; and the settings where it is acceptable (rare disease, effect size large relative to plausible confounding, randomisation infeasible). Submissions meeting the rulebook receive predictable review.","asOf":"2026-09-08","links":[{"label":"FDA Real-World Evidence programme","url":"https://www.fda.gov/science-research/science-and-research-special-topics/real-world-evidence"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["real-world-evidence","accelerated-approval","hazard-ratio"],"trials":[],"people":[],"bottlenecks":["b-trial-design","b-real-world-evidence","b-rare-cancers"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A published rulebook will increase the share of externally controlled oncology submissions that are accepted without a confirmatory-trial demand, while post-approval confirmatory results will not disagree with the external-control estimate more often than they do today for single-arm accelerated approvals.","rationale":"External controls are already used informally and inconsistently. Cases where the historical comparison misled (later overturned by randomised data) share identifiable features (immortal-time bias, mismatched lines of therapy, endpoint drift) that a rulebook can exclude.","test":"Retrospectively apply the draft rulebook to past single-arm approvals with later randomised confirmation; check whether rulebook-compliant cases had smaller estimate discrepancies. Then pilot prospectively for two years.","maturity":"early-clinical","actor":"regulator","cost":"small","horizonYears":2},{"id":"idea-data-evidence-to-adoption-tracker","kind":"idea","name":"A public tracker of how long each country takes to adopt new evidence","aka":[],"tldr":"Measure and publish, for every practice-changing result, how long it takes before most eligible patients in each country and hospital actually receive it.","summary":"The 17-year 'bench to bedside' figure is a slogan, not a measurement. Using structured treatment data and registry linkage, the time from publication to 50 percent uptake among eligible patients can be computed per country, region and centre for each practice change. The proposal funds a public dashboard of these diffusion metrics, updated quarterly, to make slow adoption visible and comparable.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Knowledge reaches practice too slowly): Morris, Wooding & Grant, The answer is 17 years, what is the question (JRSM 2011)","url":"https://doi.org/10.1258/jrsm.2011.110180"}],"tags":[],"related":["seer","globocan"],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-knowledge-diffusion","b-real-world-evidence"],"keyPapers":["paper-morris-j-r-soc-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Publishing diffusion times will reveal variation of years between countries and centres for the same evidence, and centres in the slowest quartile will improve after publication.","rationale":"What is measured and published improves; cancer survival comparisons (EUROCARE, CONCORD) drove national cancer plans, and adoption speed is a more actionable metric.","test":"Compute diffusion curves for ten practice changes since 2015 across five countries with structured data; publish; track whether laggard centres accelerate over the next two years.","maturity":"speculative","actor":"data","cost":"small","horizonYears":2},{"id":"idea-tr2-sponsor-transparency-score","kind":"idea","name":"A public transparency score for every trial sponsor, used by sites and patients","aka":[],"tldr":"Rate sponsors on whether they publish their results, share data and register outcomes honestly. Hospitals and patients can then prefer sponsors that behave well.","summary":"TrialsTracker-style dashboards already compute results-posting rates per sponsor. A composite score (results posting, time to publication, data sharing, outcome-switching audit, protocol availability) published annually and offered to hospital research offices and patient groups as a factor in choosing which trials to host or join would attach a reputational and recruitment cost to opacity.","asOf":"2026-09-08","links":[{"label":"FDAAA TrialsTracker","url":"https://fdaaa.trialstracker.net/"}],"tags":[],"related":["clinicaltrials-gov","idea-tr2-fdaaa-enforcement"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-negative-results","b-patient-voice"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Sponsors in the bottom quartile will improve their score by at least 20 points within two years of publication, and sites adopting the score in feasibility assessments will report using it.","rationale":"Public university rankings on transparency in the UK and Germany produced rapid compliance improvements. Recruitment is the resource sponsors most fear losing.","test":"Publish scores for the top 50 oncology sponsors; survey research offices on use; re-score annually.","maturity":"early-clinical","actor":"data","cost":"small","horizonYears":2},{"id":"idea-moon-public-phase1-factory","kind":"idea","name":"A public-benefit phase 1 factory that takes academic discoveries into first-in-human trials","aka":[],"tldr":"Promising academic cancer discoveries stall because nobody funds the expensive step from lab to first human trial. Build a shared public facility that does exactly that step, repeatedly.","summary":"The translational valley of death lies between validated preclinical results and a funded first-in-human study: manufacturing to clinical grade, toxicology, regulatory filing and early trial costs are beyond most academic groups and unattractive to investors before human data. NCI's NExT programme and some European infrastructures partially address this. The proposal is a purpose-built, publicly funded translation facility with in-house GMP manufacturing for biologics, cell products and small molecules, standing toxicology and regulatory teams, and a clinical unit, selecting projects competitively and retaining a public share of downstream value.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The valley of death between lab and product): Butler, Translational research: crossing the valley of death (Nature 2008)","url":"https://doi.org/10.1038/453840a"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["nci","francis-crick"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-translational-valley","b-funding-allocation"],"keyPapers":["paper-butler-nature"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"The facility moves at least ten academic assets a year into phase 1 at half the cost and time of ad hoc translation and returns value to fund itself within a decade.","rationale":"Translation is a repeatable industrial process wasted when rebuilt for each project; shared infrastructure captures the economies of scale that individual academic groups cannot.","test":"Fund one facility for five years; measure assets translated, time from selection to first patient, cost per asset, and downstream licensing or trials versus historical academic comparators.","maturity":"early-clinical","actor":"policy","cost":"large","horizonYears":5},{"id":"idea-tr2-public-combination-formulary","kind":"idea","name":"A publicly held library of investigational drugs available for academic combination trials","aka":[],"tldr":"A government or charity holds stocks of experimental cancer drugs under standing agreements, so academic doctors can test combinations without negotiating with each company separately.","summary":"NCI's CTEP investigational agent programme has run for decades but covers a narrow set of agents and mostly US sites. A broader, international formulary of investigational and newly approved agents held under pre-agreed terms (including pricing for trial use of approved drugs) would let cooperative groups design combination trials from a menu rather than by bilateral pleading.","asOf":"2026-09-08","links":[{"label":"NCI CTEP","url":"https://ctep.cancer.gov/"}],"tags":[],"related":["nci","ecog-acrin","swog","unicancer","cctg"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-combination-space","b-ip-collaboration"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Cooperative-group combination trials using formulary agents open at least twelve months faster than matched trials requiring bespoke supply negotiation.","rationale":"Drug supply is the single largest cause of delay in academic combination trials. A standing formulary shifts the negotiation to once per drug rather than once per trial.","test":"Expand an existing agent programme to a cohort of twenty agents across five companies, open to non-US cooperative groups, and time the next ten trials against historical controls.","maturity":"early-clinical","actor":"policy","cost":"medium","horizonYears":3},{"id":"lymphoma-ev-radiotherapy-free-early-hodgkin","kind":"idea","name":"A radiotherapy-free cure for early Hodgkin lymphoma that actually holds","aka":["Omitting radiotherapy in early-stage Hodgkin lymphoma","Radiotherapy-free early Hodgkin lymphoma"],"tldr":"Every attempt to drop radiotherapy from early Hodgkin lymphoma on the strength of a clear scan has cost people their remission. Changing the chemotherapy as well is the next attempt.","summary":"There is a second-order problem the trials cannot settle quickly. The late-effect figures that justify omitting radiotherapy come from patients treated with mantle fields up to 2000; modern involved-site radiotherapy delivers a fraction of that dose to a fraction of the volume, and nobody knows what its 40-year risk is. The de-escalation may be chasing a harm that has already shrunk, which is an argument for building the survivorship cohorts rather than against running the trial.","asOf":"2026-10-01","links":[],"tags":["lymphoma-evidence"],"related":["lymphoma-roadmap","idea-chemo-free-hodgkin"],"cancers":["early-stage-classical-hodgkin-lymphoma","hodgkin-lymphoma"],"sections":["radiation","adcs"],"technologies":["radiotherapy","pet-ct","adc"],"targets":["cd30"],"drugs":["brentuximab-vedotin","doxorubicin","bleomycin","vinblastine","dacarbazine"],"companies":[],"institutions":[],"pathways":[],"terms":["deauville-score","abvd-beacopp"],"trials":["radar-hodgkin","hd16","eortc-h10"],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol","b-surgery-radiation-innovation"],"keyPapers":["paper-ghsg-hd16-pet-guided-early-favourable-hodgkin-jco-2019","paper-eortc-h10-pet-adapted-early-hodgkin-jco-2017","paper-schaapveld-second-cancer-risk-40-years-hodgkin-nejm-2015"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Replacing bleomycin with brentuximab vedotin in early-stage Hodgkin lymphoma makes it possible to omit radiotherapy entirely in patients with a Deauville score of 1 to 3 after two cycles, without the loss of tumour control that HD16 and EORTC H10 recorded.","rationale":"The reason to want this is measured: 48.5 per cent of Hodgkin lymphoma survivors developed a second cancer within 40 years in the Dutch cohort, 50 per cent developed cardiovascular disease, and breast cancer risk rose eightfold above 40 Gy to the breast with no plateau. The reason it has not worked is also measured: HD16 lost 7.3 percentage points of five-year progression-free survival when radiotherapy was omitted after a negative scan, and EORTC H10 could not demonstrate non-inferiority in either risk group, with 99.0 against 87.1 per cent in the favourable group. Both trials kept ABVD and changed only the radiotherapy. RADAR changes the chemotherapy too.","test":"RADAR (NCT04685616) is the test: 1,042 patients randomised between ABVD and A2VD with radiotherapy given only for a Deauville score of 4, primary completion listed for September 2030. A positive result needs progression-free survival in the radiotherapy-free group to match the 93 to 99 per cent combined-modality benchmark, not merely to be non-inferior against a wide margin.","maturity":"being-tested-at-scale","actor":"research","cost":"large","horizonYears":5},{"id":"idea-prev-lynch-frameshift-vaccine-rct","kind":"idea","name":"A randomised trial of a shared-antigen vaccine to prevent Lynch syndrome cancers","aka":[],"tldr":"Lynch syndrome tumours share predictable mutations the immune system can target. A vaccine in early trials could be tested to see if it prevents polyps and cancers in carriers.","summary":"Lynch syndrome tumours share predictable frameshift neoantigens the immune system can target, so this idea runs a randomised phase 2/3 of the Nouscom frameshift peptide vaccine Nous-209 in carriers, on a background of aspirin, with adenoma incidence at three years as the primary endpoint and colorectal cancer incidence as secondary. Nous-209 has phase 1b immunogenicity data in Lynch carriers, and carriers have high event rates that make prevention trials feasible. The test is a 600-carrier RCT. At early-clinical maturity it addresses the bottlenecks Inherited risk is mostly unidentified and Prevention we already have is not deployed, and relates to Cancer interception vaccines for high-risk carriers.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Inherited risk is mostly unidentified): Childers et al., National estimates of genetic testing in women with breast or ovarian cancer (JCO 2017)","url":"https://doi.org/10.1200/JCO.2017.73.6314"}],"tags":[],"related":["idea-interception-vaccines"],"cancers":["colorectal","endometrial"],"sections":["prevention","immunotherapy"],"technologies":["shared-antigen-vaccine"],"targets":[],"drugs":[],"companies":["nouscom"],"institutions":[],"pathways":[],"terms":["msi","neoantigen"],"trials":[],"people":[],"bottlenecks":["b-hereditary-risk","b-prevention-adoption"],"keyPapers":["paper-childers-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Vaccination reduces adenoma incidence in Lynch carriers by at least 30% over three years.","rationale":"Frameshift neoantigens in mismatch-repair-deficient tumours are recurrent and immunogenic, and carriers have high event rates that make trials feasible.","test":"600-carrier RCT.","maturity":"early-clinical","actor":"industry","cost":"large","horizonYears":5},{"id":"idea-gbc-randomised-adjuvant-chemoradiation-r1-node-positive","kind":"idea","name":"A randomised trial of adjuvant chemoradiation after margin-positive or node-positive gallbladder cancer resection","aka":[],"tldr":"Radiotherapy after gallbladder cancer surgery rests on one 79-patient trial with no comparison arm and a US insurance database. People whose surgery left cancer at the edge or in the nodes are the ones it might help, and they have never been randomised.","summary":"SWOG S0809 gave chemotherapy then chemoradiation to 79 patients after resection with pT2 to 4, node-positive or margin-positive disease: two-year survival was 65 percent and no worse after R1 (60 percent) than R0 (67 percent) resection. Wang's SEER-Medicare nomogram (1,137 patients) predicts benefit for T2 or N1 or worse, and the NCDB validation found radiotherapy associated with lower mortality in T2 to T4 disease. NCCN lists chemoradiation as an option; the UK does not routinely offer it. POLCAGB tests radiotherapy before surgery in locally advanced disease, but the adjuvant R1 or node-positive question, where local recurrence is a real fraction of failures (14 local, 9 combined of 47 relapses in S0809), has no randomised trial.","asOf":"2026-09-24","links":[{"label":"SWOG S0809 (J Clin Oncol 2015)","url":"https://europepmc.org/article/MED/25964250"},{"label":"Wang et al.: nomogram for adjuvant chemoradiotherapy benefit in resected gallbladder cancer (J Clin Oncol 2011)","url":"https://europepmc.org/article/MED/22067404"}],"tags":["gallbladder-evidence"],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":["sbrt"],"targets":[],"drugs":["capecitabine"],"companies":["swog"],"institutions":["tata-memorial"],"pathways":[],"terms":["chemoradiation","radiotherapy","neoadjuvant-adjuvant"],"trials":["swog-s0809","polcagb","bilcap"],"people":[],"bottlenecks":["b-surgery-radiation-innovation","b-trial-enrolment"],"keyPapers":["paper-swog-s0809-adjuvant-chemoradiation-jco-2015","paper-wang-adjuvant-chemoradiotherapy-nomogram-gallbladder-cancer-jco-2011","paper-giannis-ajcc8-gallbladder-staging-validation-cancers-2021"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"After R1 or node-positive resection of gallbladder cancer, capecitabine-based chemoradiation added to adjuvant systemic therapy improves three-year locoregional recurrence-free survival by at least 15 percentage points without reducing overall survival.","rationale":"Local recurrence contributes to about half of relapses after margin-positive resection in the only prospective series; modern conformal radiotherapy has lower toxicity than the regimens of the SEER era.","test":"Randomised phase 2/3 of adjuvant systemic therapy with or without capecitabine-based chemoradiation in R1 or N+ gallbladder cancer, locoregional recurrence-free survival primary in phase 2 and overall survival in phase 3; about 300 patients, feasible only as an international cooperative-group trial.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":8},{"id":"idea-data-llm-documentation-rct-oncology","kind":"idea","name":"A randomised trial of AI scribes in oncology clinics measuring errors and time","aka":[],"tldr":"AI tools that write clinic notes are spreading fast in cancer clinics. Test them properly: do they save time, do they make mistakes about drugs and doses, and do patients notice a difference?","summary":"Ambient documentation tools built on large language models are being adopted across clinics without randomised evidence, and oncology notes carry high-stakes details (regimens, doses, trial eligibility, goals of care). The proposal is a multi-centre randomised trial of AI scribes versus usual documentation in oncology clinics, with primary outcomes of clinically significant documentation errors (blinded audit), clinician time and burnout, and patient-reported communication quality, plus a secondary analysis of structured data completeness (mCODE elements captured).","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (AI that is built but not validated or deployed): Wu et al., How medical AI devices are evaluated: limitations and recommendations from an analysis of FDA approvals (Nature Medicine 2021)","url":"https://doi.org/10.1038/s41591-021-01312-x"}],"tags":[],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-ai-validation","b-workforce"],"keyPapers":["paper-wu-nat-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"AI scribes will reduce documentation time and burnout but will introduce a non-trivial rate of clinically significant errors in oncology-specific content unless paired with structured verification, and the trial will quantify both.","rationale":"Early observational reports show time savings and occasional hallucinated content; the trade-off in oncology, where a wrong dose or regimen in the note propagates, must be measured rather than assumed.","test":"Randomise 200 oncologists across ten centres for six months; audit 5,000 notes blinded for errors; measure time, burnout and patient experience.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":2},{"id":"idea-data-ai-vs-tumour-board-rct","kind":"idea","name":"A randomised trial of AI-generated treatment recommendations versus tumour boards","aka":[],"tldr":"Test head to head whether an AI that reads the record and the evidence recommends treatments as well as a panel of experts, and whether patients do as well.","summary":"AI systems that propose treatment plans from the record and the literature have been compared with tumour boards only retrospectively, with concordance as the metric. The proposal is a prospective, randomised non-inferiority trial in a defined setting (for example, first-line metastatic NSCLC or colorectal cancer): patients are randomised to have their plan generated by the AI (with clinician sign-off and override) or by the standard board, with guideline concordance, time to treatment, trial enrolment and 12-month outcomes as endpoints, and full provenance logging for every AI recommendation.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (AI that is built but not validated or deployed): Wu et al., How medical AI devices are evaluated: limitations and recommendations from an analysis of FDA approvals (Nature Medicine 2021)","url":"https://doi.org/10.1038/s41591-021-01312-x"}],"tags":[],"related":["idea-data-tumour-board-evidence-assistant","idea-data-provenance-first-decision-support"],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-ai-validation","b-workforce","b-knowledge-diffusion"],"keyPapers":["paper-wu-nat-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"AI-generated plans with clinician sign-off will be non-inferior to tumour boards on guideline concordance and clinical outcomes and superior on time to treatment and trial referral, in the studied settings.","rationale":"Tumour board capacity is a bottleneck and boards show variable concordance; if AI can match them in defined settings, expert time can be redirected to complex cases. The claim is testable only prospectively.","test":"A 600-patient randomised non-inferiority trial in one indication across five centres; pre-registered with concordance, time to treatment and 12-month PFS endpoints.","maturity":"speculative","actor":"research","cost":"medium","horizonYears":3},{"id":"idea-tnbc-adc-sequencing-trial","kind":"idea","name":"A randomised trial of antibody-drug conjugate sequence in metastatic triple-negative breast cancer","aka":[],"tldr":"Three antibody-drug conjugates now used in triple-negative breast cancer carry the same kind of chemotherapy warhead, a topoisomerase inhibitor. Nobody has randomised which to give first or whether the second works after the first; small series suggest it often does not. With two now approved first line, the question decides what a patient gets for the rest of her life.","summary":"Sacituzumab govitecan (SN-38) and datopotamab deruxtecan and trastuzumab deruxtecan (deruxtecan) all deliver topoisomerase I inhibitor payloads; ASCENT-03, ASCENT-04 and TROPION-Breast02 moved the TROP2 conjugates to first line and DESTINY-Breast04 covers the 36.6 percent of triple-negative tumours that are HER2-low. Retrospective series of conjugate after conjugate report short progression-free survival on the second agent, consistent with payload resistance (SLFN11 loss, TOP1 mutation) rather than antigen loss, and the corpus term adc-after-adc-caution records the position. No randomised trial compares TROP2 conjugate then trastuzumab deruxtecan with the reverse, or tests chemotherapy interposition, and the ASCO 2022 biomarker guideline finds no test to guide the choice.","asOf":"2026-09-24","links":[{"label":"TROPION-Breast02 (Ann Oncol 2026)","url":"https://europepmc.org/article/MED/41937088"},{"label":"ASCENT (NEJM 2021)","url":"https://europepmc.org/article/MED/33882206"}],"tags":["tnbc-evidence"],"related":["trop2-adc-roadmap","adc-generations"],"cancers":["tnbc","her2-low-metastatic-breast-cancer"],"sections":[],"technologies":["adc","topoisomerase-inhibitors","trop2-pet"],"targets":["trop2","her2"],"drugs":["sacituzumab-govitecan","datopotamab-deruxtecan","trastuzumab-deruxtecan"],"companies":["gilead","astrazeneca","daiichi-sankyo"],"institutions":[],"pathways":[],"terms":["adc-sequencing","adc-after-adc-caution","her2-low","pfs"],"trials":["ascent","ascent-03","tropion-breast02","destiny-breast04"],"people":[],"bottlenecks":["b-resistance","b-combination-space","b-trial-design"],"keyPapers":["paper-ascent-nejm-2021","paper-tropion-breast02-ann-oncol-2026","paper-destiny-breast04-nejm-2022","paper-asco-biomarkers-metastatic-breast-cancer-guideline-jco-2022"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"In HER2-low metastatic triple-negative breast cancer progressing on a first-line TROP2 antibody-drug conjugate, immediate trastuzumab deruxtecan yields a progression-free survival hazard ratio no better than 0.85 against chemotherapy, and a biomarker of payload resistance (SLFN11 expression or TOP1 alteration in ctDNA) identifies the patients in whom it is inferior.","rationale":"Shared payload biology predicts cross-resistance; the alternative, chemotherapy between conjugates, is cheap and may restore sensitivity, and the choice is made thousands of times a year without evidence.","test":"Randomised phase 3 in HER2-low disease after first-line TROP2 conjugate: trastuzumab deruxtecan versus chemotherapy versus chemotherapy then trastuzumab deruxtecan, progression-free survival primary, with mandatory biopsy or ctDNA at progression for payload resistance markers; a parallel cohort in HER2-zero disease comparing the alternate TROP2 conjugate with chemotherapy.","maturity":"early-clinical","actor":"industry","cost":"large","horizonYears":5},{"id":"idea-data-sequencing-analysis-per-approval","kind":"idea","name":"A real-world sequencing analysis within a year of every new approval","aka":[],"tldr":"Trials tell us a drug works but not where it fits among the others. Commit to answering 'which order' from hospital data within a year of each approval.","summary":"The question clinicians face after approval is sequence: first or second line, before or after the previous standard. Trials rarely address it. The proposal is a funded programme that, for every new oncology approval, runs a pre-registered target trial emulation of sequencing strategies in federated data within 12 months, published in a standard format and fed into guidelines as explicitly graded real-world evidence.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Weak real-world evidence and registries): Gyawali, Hey & Kesselheim, Assessment of the clinical benefit of cancer drugs receiving accelerated approval (JAMA Intern Med 2019)","url":"https://doi.org/10.1001/jamainternmed.2019.0462"}],"tags":[],"related":["idea-data-federated-analytics-network"],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["real-world-evidence","adc-sequencing"],"trials":[],"people":[],"bottlenecks":["b-real-world-evidence","b-knowledge-diffusion","b-combination-space"],"keyPapers":["paper-gyawali-jama-intern-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Systematic sequencing analyses will change guideline sequencing recommendations for at least a quarter of new approvals within two years of approval, and will identify sequences associated with worse survival that were being used in practice.","rationale":"Sequencing analyses of ADCs, CDK4/6 inhibitors and immunotherapy have emerged from academic real-world studies years late; making them systematic and timely is a funding and infrastructure decision.","test":"Run the programme for one year of approvals in one federated network; count analyses delivered on time and guideline citations within 24 months.","maturity":"speculative","actor":"research","cost":"medium","horizonYears":2},{"id":"idea-reg-recovery-style-platform-repurposing","kind":"idea","name":"A RECOVERY-style permanent platform trial of cheap drugs added to cancer care","aka":[],"tldr":"The UK's RECOVERY trial answered questions about dexamethasone and other cheap COVID drugs within months by randomising tens of thousands of ordinary hospital patients with a two-page consent and routine-data follow-up. Cancer needs the same permanent platform to test generics such as statins, metformin, aspirin and propranolol added to standard care.","summary":"RECOVERY enrolled tens of thousands of patients with a two-page consent, minimal data collection and routine-data follow-up, delivering definitive answers on dexamethasone and others within months. Oncology has platform trials (GBM AGILE, STAMPEDE, I-SPY) but none dedicated to repurposed generics across common cancers. The proposal is a perpetual pragmatic platform in one or more national health systems, embedded in routine care, randomising patients with common cancers to standard care with or without a generic candidate (statin, metformin, propranolol, aspirin, vitamin D, low-dose naltrexone, itraconazole and others), with survival from registries as the primary outcome and arms added and dropped on interim analyses.","asOf":"2026-09-08","links":[{"label":"RECOVERY trial","url":"https://www.recoverytrial.net/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["cruk"],"pathways":[],"terms":["basket-umbrella-platform","os"],"trials":[],"people":[],"bottlenecks":["b-generic-repurposing","b-trial-design"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"The platform randomises at least 5,000 patients a year at a per-patient cost under $500 and delivers a definitive answer on at least one candidate every 18 months.","rationale":"The cost of a conventional phase 3 trial, not scientific uncertainty, is why repurposing questions remain open; routine-data platforms cut that cost by an order of magnitude and STAMPEDE showed the design works in oncology.","test":"Fund a two-year set-up in one national system with three initial arms; report enrolment, cost per patient and time to first interim analysis.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":4},{"id":"idea-tr2-preclinical-negative-registry","kind":"idea","name":"A registry for preclinical experiments that did not work","aka":[],"tldr":"Most lab experiments that fail are never written up, so other labs repeat them. A simple, structured registry with a citable record for each failed experiment would stop the waste.","summary":"Negative preclinical findings (a drug that did not work in a model, a target that did not validate, a biomarker that did not predict) have no home. A registry with minimal structured fields (target, model, intervention, readout, result, methods link, raw data), each with a DOI, and integrated into the major databases, would make failures findable. Funders would require deposit for supported projects.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Failures are hidden): Anderson et al., Compliance with results reporting at ClinicalTrials.gov (NEJM 2015)","url":"https://doi.org/10.1056/NEJMsa1409364"}],"tags":[],"related":["pubmed-europepmc","open-targets","idea-tr2-target-failure-index"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-negative-results","b-reproducibility"],"keyPapers":["paper-anderson-n-engl-j-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Within three years, at least 20% of active oncology labs in participating institutions deposit at least one record per year, and surveyed researchers report avoiding at least one planned experiment because of a registry entry.","rationale":"The gene-target level bias is enormous: a handful of targets attract most papers, partly because negative results on them are invisible. Registries with low friction (such as bioRxiv for preprints) achieved rapid adoption once norms shifted.","test":"Launch with three funders requiring deposit; measure deposits, views and self-reported behaviour change after two years.","maturity":"speculative","actor":"research","cost":"small","horizonYears":2},{"id":"idea-tr2-sequence-registry","kind":"idea","name":"A registry of every treatment sequence patients actually receive, with outcomes","aka":[],"tldr":"Record, for every patient, the order of treatments and what happened, so that the most common sequences can be compared and the worst ones flagged.","summary":"Approved drugs multiply faster than sequencing trials. A national or multi-centre registry capturing line-by-line therapy and outcomes (as the Flatiron and Dutch cancer registries partly do) with a public dashboard of sequence performance would let clinicians see which sequences are common and which look poor, and give trialists the effect sizes needed to design randomised sequence trials.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Too many combinations to test): Palmer & Sorger, Combination cancer therapy can confer benefit via patient-to-patient variability without drug additivity or synergy (Cell 2017)","url":"https://doi.org/10.1016/j.cell.2017.11.009"}],"tags":[],"related":["idea-tr2-pragmatic-sequence-randomisation"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["real-world-evidence","adc-sequencing"],"trials":[],"people":[],"bottlenecks":["b-combination-space","b-real-world-evidence"],"keyPapers":["paper-palmer-cell"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Publishing sequence-level outcomes will change prescribing away from the bottom-quartile sequences within two years, measurable as a fall in their share of use.","rationale":"Registry feedback changed practice in cardiac surgery and in Dutch colorectal cancer care. The data already exists; it is not assembled by sequence.","test":"Build the dashboard for metastatic breast and colorectal cancer in one health system; publish; measure change in sequence shares.","maturity":"early-clinical","actor":"data","cost":"medium","horizonYears":3},{"id":"idea-tr2-ai-external-validation-registry","kind":"idea","name":"A registry of external validation datasets for cancer AI models, with mandatory reporting","aka":[],"tldr":"Cancer AI models are usually tested on data from the same hospital they were built on. A registry of independent test datasets, and a rule that every model reports performance on at least one, would show which models really work.","summary":"Most published cancer AI models lack external validation, and performance drops sharply on data from other institutions. A curated registry of held-out datasets across modalities (pathology, radiology, genomics) hosted by neutral custodians, with a submission protocol that returns performance metrics without releasing the data, would make external validation routine. Journals and regulators would require a registry validation for any clinical claim.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Preclinical results do not reproduce): Errington et al., Investigating the replicability of preclinical cancer biology (eLife 2021)","url":"https://doi.org/10.7554/eLife.71601"}],"tags":[],"related":["idea-tr2-open-cdx-validation-sets","idea-multimodal-foundation-model"],"cancers":[],"sections":[],"technologies":["digital-pathology-ai","pathology-foundation-model"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-reproducibility","b-ai-validation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Models validated through the registry will show a median performance drop of at least ten percentage points from internal to external validation, and the requirement will improve the external performance of subsequently published models.","rationale":"Held-out evaluation servers (as in machine learning benchmarks) prevent overfitting to the test set; medicine has the datasets but not the shared infrastructure.","test":"Establish registry datasets for three tasks (HER2 scoring, lung nodule malignancy, ctDNA variant calling); validate 50 published models; report the distribution of performance changes.","maturity":"early-clinical","actor":"data","cost":"medium","horizonYears":2},{"id":"idea-fund-standard-combination-agreement","kind":"idea","name":"A regulator-endorsed standard contract for inter-company combination trials","aka":[],"tldr":"Most of the delay in testing two companies' drugs together is lawyers negotiating from scratch. A single standard agreement, blessed by regulators, would let them sign in weeks.","summary":"A model clinical collaboration agreement for combination studies, covering supply, cost sharing, safety data exchange, publication, data ownership, background and foreground IP and regulatory filing rights, developed by an industry consortium (TransCelerate or a similar body) with academic networks and endorsed by the FDA and EMA as consistent with their combination-development guidance. Companies pre-commit to accept the template without modification for trials meeting defined criteria. Standard templates have cut contract time dramatically in academic-industry clinical trial agreements (for example the UK's model Clinical Trial Agreement and the US Accelerated Clinical Trial Agreement).","asOf":"2026-09-08","links":[{"label":"TransCelerate BioPharma","url":"https://www.transceleratebiopharmainc.com/"}],"tags":[],"related":["idea-fund-combination-patent-pool","idea-fund-universal-mta-fast-lane"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-ip-collaboration","b-combination-space"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Adoption of a standard combination agreement by ten large oncology companies reduces the median time from scientific agreement to signed contract for cross-company combination trials from over twelve months to under three, and increases such trials by a third within two years.","rationale":"The UK model CTA reduced negotiation times from months to weeks across NHS trusts; TransCelerate's shared investigator platform and common protocol template show that competitors will standardise operational documents when regulators and sponsors align. Combination agreements are the last major bespoke document.","test":"Develop the template with a consortium and pilot it on twenty combination trials, measuring negotiation time and deviations from the template against a matched set of bespoke agreements.","maturity":"speculative","actor":"industry","cost":"small","horizonYears":2},{"id":"idea-bio2-antimetastatic-endpoint","kind":"idea","name":"A regulatory endpoint for drugs that block spread, not tumours","aka":[],"tldr":"Today a cancer drug is approved for shrinking tumours. A drug that stopped cancer spreading would fail that test, so almost nobody develops one. A new endpoint would fix that.","summary":"Anti-metastatic agents act on dissemination, seeding and outgrowth, not on the size of existing lesions, so they look inactive by RECIST and are killed in phase 2. A qualified endpoint family (new-lesion-free survival, number of new anatomical sites over time, and site-specific metastasis-free survival) would let sponsors run trials that can succeed. Regulators already accept metastasis-free survival in non-metastatic prostate cancer, which is the precedent to generalise.","asOf":"2026-09-08","links":[{"label":"FDA Oncology Center of Excellence (page moved; nearest live section)","url":"https://www.fda.gov/about-fda/"}],"tags":[],"related":[],"cancers":["prostate","breast-hr-positive"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["recist","oligometastatic","os"],"trials":[],"people":[],"bottlenecks":["b-metastasis-biology","b-trial-design"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"If FDA and EMA qualify a new-lesion-based endpoint family for the adjuvant and oligometastatic settings, at least five mechanistically anti-metastatic programmes that are currently shelved enter registrational trials within five years.","rationale":"Endpoint availability drives portfolio choices more than biology does: metastasis-free survival in the non-metastatic castration-resistant prostate trials created an entire treatment setting almost overnight. The same instrument applied to any cancer would make anti-seeding mechanisms commercially legible.","test":"A regulatory workshop plus a retrospective analysis pooling adjuvant trial datasets to show that new-lesion-free survival is estimable, reproducible across readers, and correlated with overall survival; then a formal endpoint qualification submission.","maturity":"speculative","actor":"regulator","cost":"small","horizonYears":5},{"id":"idea-fund-radiotherapy-innovation-pathway","kind":"idea","name":"A regulatory pathway for new radiotherapy techniques modelled on drug development","aka":[],"tldr":"New ways of giving radiotherapy are adopted without the staged testing that drugs go through, and are then hard to evaluate. A defined pathway with fee waivers and clear evidence steps would bring rigour without blocking progress.","summary":"Regulators and professional bodies define a staged pathway for radiotherapy techniques and fractionation innovations (not just machines): technical feasibility and dosimetry standards, early-phase toxicity studies with defined endpoints, randomised or registry-based comparative evaluation, and a clear route to guideline and reimbursement recognition, with regulatory fee waivers and scientific advice for academic sponsors. The machine is regulated as a device but the technique (dose, fractionation, target, adaptation strategy) is what determines outcomes, and it currently has no evidence pathway at all. Radiotherapy groups have called for this for years; making it official aligns academic sponsors, payers and regulators on what evidence is needed.","asOf":"2026-09-08","links":[{"label":"ESTRO","url":"https://www.estro.org/"}],"tags":[],"related":["idea-fund-flash-evidence-programme","idea-fund-adaptive-radiotherapy-evidence","idea-fund-radiotherapy-trials-infrastructure"],"cancers":[],"sections":[],"technologies":["flash-rt","mr-linac","sbrt","carbon-ion"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["michael-baumann","juergen-debus"],"bottlenecks":["b-surgery-radiation-innovation","b-regulatory-fragmentation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A defined pathway increases the proportion of new radiotherapy techniques entering clinical use with a prospective comparative study underway from a minority to a majority within four years, and shortens the time from first use to guideline recognition for techniques that prove beneficial.","rationale":"SBRT and hypofractionation spread for a decade on retrospective data before randomised trials confirmed benefit; FLASH and adaptive radiotherapy are following the same path. Drug development shows staged evidence requirements do not prevent innovation when the pathway is clear and supported.","test":"Pilot the pathway with three emerging techniques through a regulator-professional body partnership and compare evidence generation and time to recognition with historical techniques.","maturity":"speculative","actor":"regulator","cost":"small","horizonYears":4},{"id":"idea-data-regulatory-sandbox-adaptive-ai","kind":"idea","name":"A regulatory sandbox for continuously learning cancer AI","aka":[],"tldr":"Let AI tools that improve as they learn be used under close supervision in a few hospitals, with pre-agreed rules for what changes are allowed and how they are checked.","summary":"Regulation assumes a frozen model; models that update on new data are effectively unapprovable, so deployed models age. The FDA's predetermined change control plan is a step. The proposal is a formal sandbox: a small number of sites, a pre-specified envelope of allowed updates, mandatory shadow evaluation of each update on sequestered data before activation, full audit logs, and a regulator seat at the table, generating the evidence needed to write general rules for adaptive AI.","asOf":"2026-09-08","links":[{"label":"FDA Predetermined Change Control Plans (page moved; nearest live section)","url":"https://www.fda.gov/regulatory-information/search-fda-guidance-documents/"}],"tags":[],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-ai-validation","b-regulatory-fragmentation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Adaptive models in the sandbox will maintain or improve performance over two years while frozen comparators degrade, without safety events attributable to updates, providing the evidence for a general adaptive-AI pathway.","rationale":"Sandboxes in fintech produced workable regulation for novel products faster than rulemaking; the same approach suits AI where the risks are poorly understood in advance.","test":"Run a two-year sandbox with three adaptive models at five sites; compare performance trajectories with frozen versions; publish the regulatory learnings.","maturity":"early-clinical","actor":"regulator","cost":"medium","horizonYears":3},{"id":"idea-reg-diagnostic-reliance-pathway","kind":"idea","name":"A reliance pathway for companion diagnostics so the test arrives with the drug","aka":[],"tldr":"Targeted cancer drugs often reach a country years before the test needed to select patients is approved there. Recognising other regulators' test approvals would close the gap.","summary":"In vitro diagnostic regulation has fragmented further since the EU IVDR: a companion diagnostic cleared by FDA as a PMA needs a separate notified-body assessment in Europe and different routes in Japan, China and Brazil. Because the drug is unusable without the test, this delay is a drug access delay. The proposal is a reliance route under which a companion diagnostic approved alongside a drug by a WHO-listed authority is accepted for that indication, with local requirements limited to laboratory accreditation and proficiency testing.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Regulatory divergence between regions): FDA Oncology Center of Excellence, Project Orbis","url":"https://www.fda.gov/about-fda/oncology-center-excellence/project-orbis"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["companion-diagnostic"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["companion-diagnostic-term"],"trials":[],"people":[],"bottlenecks":["b-regulatory-fragmentation","b-biomarker-validation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Countries adopting diagnostic reliance reduce the gap between drug approval and reimbursed availability of its companion test from a median of over a year to under six months.","rationale":"Analytical and clinical validation of a companion test does not vary by geography, and the test's clinical utility was already established in the pivotal drug trial that every regulator reviews.","test":"Survey the drug-to-test availability gap for ten recent targeted oncology approvals across 20 countries to size the problem; then pilot reliance in three countries and remeasure.","maturity":"speculative","actor":"regulator","cost":"small","horizonYears":3},{"id":"idea-tr2-replication-status-badge","kind":"idea","name":"A replication status badge on every cancer paper, visible in PubMed","aka":[],"tldr":"When you look up a paper, you should immediately see whether anyone has tried to repeat it and whether they succeeded.","summary":"Replication status is scattered across follow-up papers, preprints and comments (PubPeer). A curated, structured layer linking each paper to registered replication attempts and their outcomes (replicated, partially, failed, not attempted), displayed alongside abstracts in PubMed and Europe PMC via existing annotation mechanisms, would make reproducibility visible at the point of reading and reward replicators with attribution.","asOf":"2026-09-08","links":[{"label":"PubPeer","url":"https://pubpeer.com/"}],"tags":[],"related":["pubmed-europepmc","idea-tr2-retraction-propagation","idea-tr2-replication-bounties"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-reproducibility","b-knowledge-diffusion"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Papers with a displayed 'failed replication' status will see a decline in uncritical citation (citing as established fact) of at least a third within two years.","rationale":"Retracted papers continue to be cited because the status is not visible where readers look; the same fix applies to replication.","test":"Annotate 1,000 high-impact cancer papers; deploy the badge via Europe PMC annotations; analyse citation context before and after.","maturity":"speculative","actor":"data","cost":"small","horizonYears":2},{"id":"idea-fund-repurposing-indication-exclusivity","kind":"idea","name":"A repurposing label pathway with short exclusivity that non-profits can hold","aka":[],"tldr":"Create a way for a charity or university to get a cheap old drug officially approved for a new cancer use, with a few years of protection on that use so trial costs can be recovered without high prices.","summary":"A dedicated regulatory pathway for new oncology indications of off-patent drugs, accessible to non-commercial sponsors, with three to five years of indication-specific data exclusivity that can be assigned to a non-profit or public body. The exclusivity is for reimbursement of the indication rather than for the molecule, so generic supply for existing uses is unaffected; a modest per-indication payment from payers repays the trial. Without this, academic repurposing results cannot reach the label and remain off-label and unevenly used.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Incentives reward me-too drugs and marginal gains): Upadhaya et al., PD1/PDL1 inhibitor clinical trial landscape (Nat Rev Drug Discov 2022)","url":"https://doi.org/10.1038/d41573-022-00030-4"}],"tags":[],"related":["idea-fund-open-source-repurposing-leads","idea-fund-nonprofit-pharma","idea-fund-shelved-asset-escrow"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-incentive-misalignment","b-generic-repurposing"],"keyPapers":["paper-upadhaya-nat-rev-drug-discov"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A repurposing pathway with assignable indication exclusivity increases label changes for off-patent drugs in oncology from near zero to several per year within five years and raises guideline adoption of positive academic repurposing trials.","rationale":"The EU's STAMP working group and the Belgian and Dutch repurposing frameworks have identified the missing label pathway as the key barrier; the orphan-drug precedent shows that indication-level exclusivity can be designed. The Anticancer Fund's and Cures Within Reach's pipelines provide immediate candidates.","test":"Legislate a pilot pathway in one region and run two repurposing labels through it, measuring time to label, payer uptake and price.","maturity":"speculative","actor":"regulator","cost":"small","horizonYears":4},{"id":"idea-fund-metastasis-moonshot","kind":"idea","name":"A ring-fenced metastasis programme with metastasis-specific endpoints","aka":[],"tldr":"Metastasis causes about nine in ten cancer deaths but gets a small slice of research money. This would ring-fence a tenth of national cancer research budgets for the biology and trials of spread itself.","summary":"A dedicated, multi-year programme funds metastasis biology (dissemination, dormancy, organ-specific colonisation), metastasis-directed therapies and, crucially, trials whose primary endpoint is the prevention or delay of new metastases rather than shrinkage of existing ones. It would include model-building (autochthonous and humanised metastasis models), a metastatic tissue banking network with rapid autopsy, and a trial arm for 'anti-metastatic' agents tested in the adjuvant and molecular residual disease setting where they can plausibly work.","asOf":"2026-09-08","links":[{"label":"Cancer Grand Challenges","url":"https://cancergrandchallenges.org/"}],"tags":[],"related":["idea-ctdna-escalation-tnbc","idea-fund-brain-metastases-programme"],"cancers":["pancreatic","tnbc","melanoma","colorectal"],"sections":[],"technologies":["mrd-testing","pdx-models"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["mrd","ctdna","oligometastatic"],"trials":[],"people":["klaus-pantel"],"bottlenecks":["b-funding-allocation","b-metastasis-biology"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Ring-fencing 10% of a national cancer research budget for metastasis for a decade at least triples the number of registered interventional trials with a metastasis-prevention primary endpoint and produces at least one approved agent labelled for prevention of metastatic relapse.","rationale":"Analyses of NCI portfolios have found metastasis-specific research at a few percent of spend despite its share of mortality; the Metastasis Research Society and the UK's Cancer Grand Challenges have argued that the field is starved of models and of trial designs that can show anti-metastatic effect. Ring-fencing worked to create fields in HIV cure research and in paediatric oncology through the Children's Oncology Group.","test":"Portfolio audit at baseline, then a funded pilot of 3 to 5 metastasis-prevention trials in high-risk resected disease (for example pancreatic, TNBC, melanoma) using ctDNA-defined populations; success is feasibility of accrual, endpoint acceptance by regulators, and a signal in at least one trial within six years.","maturity":"speculative","actor":"policy","cost":"large","horizonYears":8},{"id":"idea-acc-risk-stratified-cardio-oncology-pathway","kind":"idea","name":"A risk-stratified cardio-oncology pathway for everyone receiving heart-toxic cancer therapy","aka":[],"tldr":"Some chemotherapy and antibody drugs damage the heart. Checking heart function before and during treatment and starting protective drugs early for those at risk could prevent much of that damage.","summary":"Anthracyclines, HER2-targeted therapy, and some kinase inhibitors cause cardiac dysfunction that is often detected late. Guidelines (ESC 2022 cardio-oncology) recommend baseline risk assessment, biomarker and strain-imaging surveillance, and cardioprotective therapy for high-risk patients, but implementation is inconsistent and cardio-oncology clinics are rare outside academic centres. A pathway with automatic risk scoring at prescription, scheduled surveillance, and protocolised initiation of protective therapy would standardise this.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Survivorship and late effects are neglected): NCI Office of Cancer Survivorship statistics","url":"https://cancercontrol.cancer.gov/ocs/statistics"}],"tags":[],"related":[],"cancers":["breast-her2-positive","dlbcl"],"sections":["supportive-care","rejuvenation"],"technologies":["cardio-oncology"],"targets":[],"drugs":["trastuzumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Systematic risk-stratified cardio-oncology care will reduce the incidence of symptomatic heart failure within five years of treatment by at least 30% and reduce premature discontinuation of HER2-targeted therapy.","rationale":"Early detection of subclinical dysfunction and prompt cardioprotection improve recovery in trials; the gap is systematic application rather than evidence.","test":"A cluster-randomised implementation across 20 hospitals with heart failure incidence, treatment completion, and cardiovascular death as endpoints.","maturity":"being-tested-at-scale","actor":"clinic","cost":"medium","horizonYears":3},{"id":"idea-bio2-rare-cancer-telepathology-network","kind":"idea","name":"A same-week expert second opinion for every rare cancer diagnosis","aka":[],"tldr":"Rare cancers are often misdiagnosed, which sends patients down the wrong treatment path. Digital slide sharing could get every case to an expert within days.","summary":"Reference pathology review changes the diagnosis in a substantial minority of sarcoma and rare tumour cases, and diagnosis determines treatment entirely. European reference networks and national sarcoma review panels show the model works, but coverage is incomplete and turnaround is slow. Whole-slide imaging plus a funded expert rota plus AI pre-screening for likely rare entities would make it universal.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Rare and paediatric cancers without markets): Gatta et al., Rare cancers are not so rare: the rare cancer burden in Europe (EJC 2011)","url":"https://doi.org/10.1016/j.ejca.2011.08.008"}],"tags":[],"related":[],"cancers":["sarcoma","neuroendocrine","thyroid"],"sections":[],"technologies":["digital-pathology-ai","pathology-foundation-model","histopathology-ihc"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["sarcoma-histotype-tailoring"],"trials":[],"people":["alessandro-gronchi","jean-yves-blay","marco-guzzo"],"bottlenecks":["b-rare-cancers","b-care-fragmentation","b-workforce"],"keyPapers":["paper-gatta-eur-j-cancer"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Mandatory digital reference review for suspected rare cancers changes diagnosis or management in at least 15% of cases and improves guideline-concordant treatment, with median turnaround under seven days.","rationale":"Centralised review already improves outcomes in sarcoma when patients are managed in reference centres. Digital pathology removes the physical slide logistics that limited previous schemes, and AI triage can flag which cases need expert eyes.","test":"A regional programme with mandatory digital review for a defined list of rare diagnoses, reporting diagnostic change rate, turnaround and downstream treatment concordance.","maturity":"being-tested-at-scale","actor":"clinic","cost":"medium","horizonYears":4},{"id":"idea-reg-shared-ai-review-assistant","kind":"idea","name":"A shared AI review assistant that maps one dossier to every regulator's questions","aka":[],"tldr":"Regulators are starting to use AI to read dossiers faster. If they shared one tool, it could show where their questions overlap and where they truly disagree.","summary":"FDA deployed an internal generative AI assistant agency-wide in 2025; EMA and MHRA have pilots. Each is used in isolation. The proposal is a jointly governed assistant with an audit trail that, for a given dossier, drafts the assessment sections for each participating agency's template, flags inconsistencies between the dossier and the trial registry, and surfaces where two agencies' historical decisions on similar evidence diverged. Reviewers retain all decisions; the tool exposes divergence.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Regulatory divergence between regions): FDA Oncology Center of Excellence, Project Orbis","url":"https://www.fda.gov/about-fda/oncology-center-excellence/project-orbis"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-regulatory-fragmentation","b-ai-validation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Reviews using the shared assistant take at least 30% fewer reviewer-hours per oncology dossier and produce information requests to sponsors that overlap by more than 80% between agencies, up from an unmeasured but lower baseline.","rationale":"The bulk of review time is reading and cross-referencing, which large language models do well under supervision; a shared tool makes the tacit differences between agencies explicit and therefore fixable.","test":"Run the assistant retrospectively on 30 completed Orbis dossiers and compare its drafted assessments with the agencies' actual reports; then run prospectively in a reviewer-in-the-loop pilot.","maturity":"early-clinical","actor":"regulator","cost":"medium","horizonYears":3},{"id":"idea-bio2-shared-compound-access-pool","kind":"idea","name":"A shared compound library that rare cancer researchers can actually use","aka":[],"tldr":"Companies hold thousands of well-characterised drugs that could help rare cancers, but each request takes a year of legal negotiation. One standing agreement would unblock it.","summary":"Academic rare cancer groups routinely fail to obtain clinical-grade compound for investigator-initiated trials because material transfer and intellectual property negotiation exceed the capacity of small teams. A pre-negotiated multi-company access pool (standard terms, a single application route, an independent scientific review committee and mandatory data return) would industrialise access. Precedents exist in structural genomics consortia and in some public-private compound-sharing schemes.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Rare and paediatric cancers without markets): Gatta et al., Rare cancers are not so rare: the rare cancer burden in Europe (EJC 2011)","url":"https://doi.org/10.1016/j.ejca.2011.08.008"}],"tags":[],"related":["drugbank-chembl","clinicaltrials-gov"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["nci","esmo"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-rare-cancers","b-ip-collaboration","b-translational-valley"],"keyPapers":["paper-gatta-eur-j-cancer"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A standing access pool with standard terms reduces median time from request to compound receipt from over 12 months to under 3, and increases investigator-initiated rare cancer trials measurably within three years.","rationale":"Open science consortia have shown that pre-agreed standard terms remove the dominant transaction cost in cross-institution collaboration. Companies gain rare-indication data at almost no cost and retain their commercial position.","test":"Recruit five companies and 20 compounds into a pilot pool, then publish the median time to access and the number of trials initiated in the first two years.","maturity":"speculative","actor":"industry","cost":"medium","horizonYears":5},{"id":"idea-fund-control-arm-commons","kind":"idea","name":"A shared library of pooled control arms to shrink and speed future trials","aka":[],"tldr":"Thousands of patients have received standard treatment in the control arms of past trials. Pooling their anonymised data would let new trials borrow from them and randomise fewer patients to old treatments.","summary":"A curated commons of individual patient data from control arms of completed oncology trials, standardised by indication, line of therapy and era, with covariates sufficient for matching and Bayesian borrowing, governed by the data trust and accepted by regulators as a source for external or hybrid control arms under pre-specified conditions. Sponsors contributing control data receive access rights. Regulators (FDA's real-world evidence and complex innovative design programmes, EMA's qualification opinions) have signalled openness to external controls where data quality is high; the commons provides the quality and the scale.","asOf":"2026-09-08","links":[{"label":"Project Data Sphere","url":"https://www.projectdatasphere.org/"}],"tags":[],"related":["idea-fund-trial-data-trust","idea-fund-neutral-platform-sponsor"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["real-world-evidence","standard-of-care"],"trials":[],"people":[],"bottlenecks":["b-ip-collaboration","b-trial-design","b-trial-enrolment"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Trials using commons-derived hybrid controls under pre-agreed methodology reach the same conclusions as fully randomised trials in retrospective emulation for at least 90% of tested cases, and their prospective use reduces control-arm enrolment by a third in rare and late-line indications.","rationale":"Project Data Sphere's pooled control arms have already supported prognostic models and trial design; regulatory acceptance of external controls has grown for rare diseases. Oncology has the volume of standardised trial data to make borrowing statistically credible.","test":"Assemble commons data for three indications, run pre-registered emulations of recent randomised trials, and pilot a prospective hybrid-control trial with regulatory agreement.","maturity":"early-clinical","actor":"data","cost":"medium","horizonYears":3},{"id":"idea-tr1-window-of-opportunity-default","kind":"idea","name":"A short pre-surgery drug window as the default early test of new agents","aka":[],"tldr":"Between diagnosis and surgery there are usually a few weeks. Giving a new drug in that window and comparing the tumour before and after surgery shows whether it hits its target in real people, quickly and cheaply.","summary":"Window-of-opportunity trials give a short course of an investigational agent between diagnostic biopsy and definitive surgery, with paired tissue for pharmacodynamic, proliferation (Ki-67) and immune readouts, and ctDNA dynamics. The proposal is to make a window study a standard early step for agents with a tissue biomarker, with cancer centres maintaining a standing window-trial pathway (consent, scheduling, sample handling) that any agent can slot into.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Trial design, endpoints and cost): Davis et al., Availability of evidence of benefits on survival and quality of life of cancer drugs approved by EMA 2009-13 (BMJ 2017)","url":"https://doi.org/10.1136/bmj.j4530"}],"tags":[],"related":[],"cancers":["breast-hr-positive","prostate","head-and-neck"],"sections":[],"technologies":["single-cell-spatial","histopathology-ihc"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["neoadjuvant-adjuvant","ctdna"],"trials":[],"people":[],"bottlenecks":["b-trial-design","b-translational-valley","b-biomarker-validation"],"keyPapers":["paper-davis-bmj"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Agents showing target modulation in a window study will succeed in later phases at a higher rate than agents without such evidence, and window studies will kill inactive agents earlier and cheaper.","rationale":"Pre-surgical endocrine and CDK4/6 window studies predicted later trial outcomes through Ki-67 change; the design gives human pharmacodynamic proof-of-mechanism with 20-40 patients.","test":"Fund a standing window-trial pathway at five centres and track the correlation between window-study pharmacodynamic outcomes and subsequent phase 2 success for the agents tested.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":3},{"id":"idea-prev-bundled-cancer-check-at-60","kind":"idea","name":"A single 'cancer check at 60' appointment bundling all screening tests","aka":[],"tldr":"People are invited separately for bowel, breast, cervical and lung screening, and partial participation is common. One appointment at 50 and 60, modelled on the NHS Health Check, offering every eligible test plus family history and risk assessment with navigation support, would raise uptake.","summary":"People are invited separately for bowel, breast, cervical and lung screening and often complete only some, so this idea offers a single bundled visit at 50 and 60, modelled on the NHS Health Check, providing a FIT kit, mammogram or HPV self-sample booking, lung risk assessment, family history capture and where applicable germline or polygenic testing, with navigation support. Fragmented invitations lead to partial participation; one decision beats four, and navigation is proven to raise uptake. The test is an RCT of bundled versus separate invitations in 20,000 people. Speculative in maturity, it addresses the bottlenecks The hardest cancers are found late, Prevention we already have is not deployed and Fragmented care and guideline gaps.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The hardest cancers are found late): Crosby et al., Early detection of cancer (Science 2022)","url":"https://doi.org/10.1126/science.aay9040"}],"tags":[],"related":[],"cancers":[],"sections":["early-detection","prevention"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-early-detection","b-prevention-adoption","b-care-fragmentation"],"keyPapers":["paper-crosby-science"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A bundled appointment increases the proportion of people fully up to date on all eligible screening by at least 15 percentage points.","rationale":"One decision beats four; patient navigation is proven to raise uptake.","test":"RCT of bundled invitation versus standard separate invitations in 20,000 people.","maturity":"speculative","actor":"policy","cost":"medium","horizonYears":3},{"id":"idea-tr2-tmb-calibration-standard","kind":"idea","name":"A single calibrated tumour mutational burden across all sequencing panels","aka":[],"tldr":"Tumour mutational burden decides who gets immunotherapy in some settings, but every sequencing panel calculates it differently. A shared calibration would make the number mean the same thing everywhere.","summary":"The Friends of Cancer Research TMB Harmonization Project showed that panel-derived TMB values can be aligned to whole-exome TMB with panel-specific calibration and reference samples. Yet the pembrolizumab approval for TMB above 10 mutations per megabase was tied to a single assay. Requiring each panel to report a calibrated TMB traceable to a common reference set, with published calibration curves, would make the biomarker portable across assays.","asOf":"2026-09-08","links":[{"label":"Friends of Cancer Research TMB Harmonization","url":"https://friendsofcancerresearch.org/tmb/"}],"tags":[],"related":["foundation-medicine","tempus"],"cancers":[],"sections":[],"technologies":["wes-wgs"],"targets":[],"drugs":["pembrolizumab"],"companies":[],"institutions":[],"pathways":[],"terms":["tmb","ngs"],"trials":[],"people":[],"bottlenecks":["b-biomarker-validation","b-immunotherapy-response"],"keyPapers":["paper-keynote-189-nejm-2018","paper-keynote-564-nejm-2021"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Calibrated TMB reporting will reduce the inter-assay disagreement in classifying tumours as TMB-high from around 20 to 30% to under 10%.","rationale":"The harmonisation project has already provided the method and reference cell lines; adoption, not science, is the gap.","test":"Have ten commercial panels report calibrated TMB on a shared 100-sample set; measure classification agreement before and after calibration.","maturity":"early-clinical","actor":"industry","cost":"small","horizonYears":2},{"id":"idea-fund-trial-data-trust","kind":"idea","name":"A single oncology trial data trust with mandatory deposit within eighteen months","aka":[],"tldr":"Every cancer trial's anonymised patient-level data would go into one trusted repository within eighteen months of completion, with a single access committee, so researchers can re-analyse, pool and learn from trials that today stay locked up.","summary":"Consolidate the existing sharing platforms (Vivli, Project Data Sphere, YODA, ClinicalStudyDataRequest) into a single oncology data trust with a legal duty to deposit individual participant data, protocols and analysis code within eighteen months of primary completion for all trials whose results support a regulatory decision or that receive public funding. One independent access committee, standard data formats (CDISC), a secure analysis environment and a public catalogue. Trials in oncology already have among the highest voluntary sharing rates but access remains slow and fragmented, and negative or discontinued trials are rarely deposited at all.","asOf":"2026-09-08","links":[{"label":"Vivli","url":"https://vivli.org/"},{"label":"Project Data Sphere","url":"https://www.projectdatasphere.org/"},{"label":"YODA Project","url":"https://yoda.yale.edu/"}],"tags":[],"related":["clinicaltrials-gov","idea-fund-control-arm-commons","idea-fund-trial-biospecimen-commons","idea-fund-stalled-asset-registry"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["real-world-evidence"],"trials":[],"people":[],"bottlenecks":["b-ip-collaboration","b-negative-results","b-data-silos"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Mandatory deposit raises the proportion of registration oncology trials with accessible individual participant data from a minority to above 80% within three years, and the median time from request to data access falls below sixty days.","rationale":"The EMA's clinical data publication policy and the ICMJE data-sharing statement requirement increased availability without harming sponsors; pooled analyses from shared data (for example Project Data Sphere control-arm analyses) have already produced prognostic tools and answered questions no single trial could.","test":"A group of funders and one regulator make deposit a condition of funding and approval for two years; measure deposit compliance, access time and the number of secondary analyses published.","maturity":"early-clinical","actor":"data","cost":"medium","horizonYears":3},{"id":"idea-bio2-implanted-ultrasound-repeat-dosing","kind":"idea","name":"A skull ultrasound implant that opens the barrier at every cycle","aka":[],"tldr":"A small ultrasound device implanted in the skull can be switched on at each chemotherapy visit to briefly open the brain barrier, letting drugs in every cycle.","summary":"Implantable ultrasound emitters have been used in recurrent glioblastoma trials with carboplatin and with albumin-bound paclitaxel, showing repeated safe barrier opening and increased brain drug concentrations. The remaining questions are whether the added exposure translates into survival, and which drug benefits most from repeated opening.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The brain: barrier and sanctuary): Stupp et al., Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma (NEJM 2005)","url":"https://doi.org/10.1056/NEJMoa043330"}],"tags":[],"related":["idea-fus-plus-adc-glioma"],"cancers":["glioblastoma"],"sections":[],"technologies":["bbb-focused-ultrasound","cytotoxic-chemotherapy"],"targets":[],"drugs":["carboplatin","paclitaxel","temozolomide"],"companies":[],"institutions":[],"pathways":[],"terms":["blood-brain-barrier"],"trials":["nct05902169"],"people":[],"bottlenecks":["b-brain-delivery"],"keyPapers":["paper-carboplatin-glioblastoma-neuro-oncol-2003","paper-carboplatin-glioblastoma-neuro-oncol-2015","paper-carboplatin-glioblastoma-eur-j-cancer-2017"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Repeated implant-mediated barrier opening at least doubles parenchymal drug concentration and improves progression-free survival in recurrent glioblastoma compared with the same drug without sonication.","rationale":"Concentration is the most plausible reason systemic agents fail in glioma, and repeated opening turns a one-off intervention into a dosing strategy that matches chemotherapy cycles. Human safety across multiple sonications is already reported.","test":"A randomised trial of drug plus sonication versus drug alone in recurrent glioblastoma, with a pharmacokinetic substudy in patients undergoing subsequent resection.","maturity":"early-clinical","actor":"industry","cost":"medium","horizonYears":6},{"id":"idea-reg-repurposing-social-impact-bond","kind":"idea","name":"A social impact bond: investors fund a repurposing trial, payers repay from savings","aka":[],"tldr":"If a cheap old drug could replace or reduce an expensive cancer treatment, health systems save money. Investors could fund the trial and be repaid from those savings if it works.","summary":"Some repurposing questions have direct payer savings attached: a generic that reduces relapse (fewer expensive second-line treatments), replaces a costly supportive drug, or allows de-escalation. The proposal is a development impact bond in which investors fund the trial, an independent evaluator verifies the result and the projected savings, and one or more payers repay investors with a return only if the trial is positive and the intervention is adopted. Outcome-based bonds have funded health interventions in India and the UK; none has funded a cancer trial.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (No incentive to repurpose cheap drugs): Pantziarka et al., The Repurposing Drugs in Oncology (ReDO) Project (ecancer 2014)","url":"https://doi.org/10.3332/ecancer.2014.442"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-generic-repurposing","b-funding-allocation"],"keyPapers":["paper-pantziarka-ecancermedicalscience"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"At least one repurposing trial is financed through a bond within three years, and the structure delivers a positive return to investors in the event of a positive result while costing payers less than 10% of the verified savings.","rationale":"The bond converts a payer's future savings into present trial funding without the payer bearing the risk of a negative result, matching the incentive of the party that benefits with the cost of generating the evidence.","test":"Identify three candidate trials with quantifiable payer savings, structure one bond with a national payer and impact investors, and run the trial with pre-registered adjudication.","maturity":"speculative","actor":"payer","cost":"medium","horizonYears":5},{"id":"idea-tr2-combination-template-agreement","kind":"idea","name":"A standard cross-company combination agreement that takes weeks, not years, to sign","aka":[],"tldr":"Companies with drugs that might work together rarely test them because the legal negotiation takes longer than the trial. A pre-written standard contract would fix that.","summary":"The CRUK Combinations Alliance and NCI CTEP show that a neutral third party with template agreements can run combination studies across companies. Extending this to an industry-wide, pre-negotiated 'combination clinical trial agreement' (like the standard licences in software) covering supply, data, publication, IP on combination findings and a default revenue rule would remove the largest non-scientific barrier.","asOf":"2026-09-08","links":[{"label":"NCI CTEP","url":"https://ctep.cancer.gov/"}],"tags":[],"related":["cruk","nci"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-combination-space","b-ip-collaboration"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Adoption of a template agreement by at least ten large sponsors will halve the median time from combination hypothesis to first patient dosed in academic-led cross-company combination trials.","rationale":"Standard material transfer and clinical trial agreements (for example the Accelerated Clinical Trial Agreement in the US) have already cut academic site contracting times. The combination-specific clauses (who owns a method-of-use patent, who supplies free drug) are the ones that stall.","test":"Draft with a neutral convenor (for example a cancer charity plus a trade body), sign with a coalition of sponsors, and measure time-to-agreement and time-to-first-patient for the next twenty combination trials versus the twenty before.","maturity":"early-clinical","actor":"industry","cost":"small","horizonYears":2},{"id":"idea-data-ai-pathology-evaluation-standard","kind":"idea","name":"A standard evaluation pathway for AI-assisted pathology, from reader study to deployment","aka":[],"tldr":"Pathology AI is cleared on uneven evidence, often without showing that pathologists using it do better than without. The proposed standard has two stages: a pre-registered, fully crossed multi-reader multi-case study comparing pathologist plus AI with pathologist alone, then a prospective deployment study measuring turnaround, tumour board discordance and treatment changes.","summary":"Pathology AI is cleared on varied evidence, often without showing that pathologists using it perform better than without. The proposal is a standard two-stage pathway: a multi-reader multi-case study with a fully crossed design, pre-registered and adequately powered, measuring pathologist-plus-AI versus pathologist alone on diagnostic accuracy and time; then a prospective deployment study measuring turnaround, discordance at tumour boards, and downstream treatment changes, all reported to the registry.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (AI that is built but not validated or deployed): Wu et al., How medical AI devices are evaluated: limitations and recommendations from an analysis of FDA approvals (Nature Medicine 2021)","url":"https://doi.org/10.1038/s41591-021-01312-x"}],"tags":[],"related":["idea-ai-her2-low-scoring"],"cancers":[],"sections":["ai-computation"],"technologies":["digital-pathology-ai","histopathology-ihc"],"targets":[],"drugs":[],"companies":["paige","pathai"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-ai-validation"],"keyPapers":["paper-wu-nat-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Applying the standard will show that a minority of pathology AI tools improve pathologist accuracy in a fully crossed design, and those that do will show measurable turnaround and treatment-decision benefits in deployment.","rationale":"Radiology has decades of reader-study methodology; pathology AI has borrowed the tools inconsistently. Standardisation makes results comparable and procurement rational.","test":"Apply the pathway to five cleared pathology AI tools (for example prostate biopsy detection, HER2 scoring, mitotic counting); publish results in a common format.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":2},{"id":"idea-bio1-evolvability-index","kind":"idea","name":"A standard evolvability score for every tumour","aka":[],"tldr":"Some tumours change fast and escape drugs quickly; others are stable. A single validated score for how evolvable a tumour is would tell doctors how aggressively to combine treatments.","summary":"Copy-number heterogeneity, whole-genome doubling, chromosomal instability signatures, APOBEC activity and ctDNA turnover each predict evolution and relapse in separate studies. The proposal is to define, freeze and prospectively validate one composite evolvability index computed from routine sequencing, analogous to how tumour mutational burden was standardised.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Tumour heterogeneity and clonal evolution): Gerlinger et al., Intratumor heterogeneity and branched evolution (NEJM 2012)","url":"https://doi.org/10.1056/NEJMoa1113205"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["wes-wgs","cgp"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["mutational-signature","tmb"],"trials":[],"people":[],"bottlenecks":["b-tumor-heterogeneity","b-biomarker-validation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"An evolvability index in the top quartile predicts shorter duration of response to single-agent targeted therapy across tumour types, and randomising high-index patients to upfront combinations improves progression-free survival.","rationale":"TRACERx subclonal copy-number heterogeneity predicts recurrence; chromosomal instability scores predict metastasis; measures of evolvability are more general than any single mutation and could guide intensity of therapy.","test":"Consortium defines the index on existing multi-region cohorts, locks it, and validates on three independent trial datasets; then a randomised trial of monotherapy versus combination stratified by index.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":4},{"id":"idea-data-drift-monitoring-standard","kind":"idea","name":"A standard for monitoring AI performance drift with pause thresholds","aka":[],"tldr":"Set common rules for how hospitals check that an AI tool still works as the scanners, patients and practices around it change, and when it must be switched off.","summary":"Model performance shifts when scanners, staining protocols, populations or clinical practice change. Few deployments monitor this. The proposal is a technical standard: a per-site reference dataset re-scored monthly, input distribution monitoring, calibration and subgroup checks, pre-specified thresholds for alert and pause, and a documented recalibration or retraining pathway, integrated with the vendor's change control plan and reported to the registry.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (AI that is built but not validated or deployed): Wu et al., How medical AI devices are evaluated: limitations and recommendations from an analysis of FDA approvals (Nature Medicine 2021)","url":"https://doi.org/10.1038/s41591-021-01312-x"}],"tags":[],"related":["idea-data-ai-post-market-performance-reporting"],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-ai-validation"],"keyPapers":["paper-wu-nat-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Sites following the drift standard will detect degradation months earlier than unmonitored sites and avoid patient harm events attributable to silent drift.","rationale":"Industrial machine learning monitors drift as routine engineering practice; healthcare deployments largely do not, and the few audits done have found drift within a year or two of deployment.","test":"Implement the standard at ten sites running the same pathology or radiology model; compare detected drift events and time to detection with ten unmonitored sites over two years.","maturity":"early-clinical","actor":"engineering","cost":"small","horizonYears":2},{"id":"idea-tr1-tumour-agnostic-approval-standard","kind":"idea","name":"A standard for tumour-agnostic approvals: minimum histologies and hierarchical modelling","aka":[],"tldr":"Some drugs are approved for any cancer with a particular mutation. Clear rules on how many cancer types must be tested, and how to combine results across them, would make these approvals more consistent and faster.","summary":"Regulators publish a standard for tissue-agnostic evidence: a minimum number of histologies with a minimum number of evaluable patients each, a Bayesian hierarchical model for borrowing across histologies with pre-specified heterogeneity thresholds, and rules for excluding histologies that show no activity. Sponsors design basket trials to the standard, and approvals list the histologies supporting them.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Trial design, endpoints and cost): Davis et al., Availability of evidence of benefits on survival and quality of life of cancer drugs approved by EMA 2009-13 (BMJ 2017)","url":"https://doi.org/10.1136/bmj.j4530"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":["ntrk","braf","ret"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["tumour-agnostic","basket-umbrella-platform","msi","gene-fusion"],"trials":[],"people":[],"bottlenecks":["b-trial-design","b-rare-cancers","b-regulatory-fragmentation"],"keyPapers":["paper-davis-bmj"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A published standard will reduce time to tumour-agnostic approval for genuinely histology-independent effects and prevent extension to histologies where effect is absent.","rationale":"Existing tumour-agnostic approvals (MSI-high, NTRK, BRAF V600E, RET) were reviewed case by case; basket trial statistics for cross-histology borrowing are mature and would benefit from regulatory commitment.","test":"Apply the draft standard retrospectively to past tumour-agnostic submissions and check consistency of decisions; then prospectively for the next three submissions.","maturity":"speculative","actor":"regulator","cost":"small","horizonYears":2},{"id":"idea-acc-transition-handoff-medication-reconciliation","kind":"idea","name":"A standard handoff with medication reconciliation at every cancer care transition","aka":[],"tldr":"Cancer care has more handoffs than most conditions, hospital to home, surgery to chemotherapy, oncology back to the family doctor, and information and medications are lost at each. A standard handoff checklist plus pharmacist medication reconciliation covering oral anticancer drugs, steroids, anticoagulants and opioids at every transition would prevent avoidable adverse drug events cheaply.","summary":"Cancer care involves more transitions than most conditions, and each is a point where information and medications are lost or duplicated. Standardised handoff tools and pharmacist-led medication reconciliation reduce adverse drug events in general medicine; oncology-specific versions covering oral anticancer agents, steroids, anticoagulants, and opioids are rare. Implementing them as a required step at defined transitions is inexpensive.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Fragmented care and guideline gaps): Hanna et al., Mortality due to cancer treatment delay: systematic review and meta-analysis (BMJ 2020)","url":"https://doi.org/10.1136/bmj.m4087"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-care-fragmentation","b-aging-comorbidity","b-toxicity-qol"],"keyPapers":["paper-hanna-bmj"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Standard transition handoffs with reconciliation will reduce medication discrepancies at transitions by at least 50% and reduce 30-day readmissions after discharge by 10%.","rationale":"Transition interventions have consistent evidence in heart failure and surgery; oncology patients have higher medication complexity and more transitions.","test":"Run a stepped implementation across a cancer network with discrepancy audits, adverse drug events, and readmissions as endpoints.","maturity":"early-clinical","actor":"clinic","cost":"small","horizonYears":1},{"id":"idea-moon-brain-delivery-platform","kind":"idea","name":"A standard platform to get drugs into the brain: focused ultrasound plus shuttle-engineered therapeutics","aka":[],"tldr":"Most cancer drugs cannot cross into the brain. Combine ultrasound that briefly opens the barrier with drugs engineered to be carried across, and make this a standard platform for every brain tumour and brain metastasis.","summary":"The blood-brain barrier excludes most antibodies and many small molecules, limiting therapy for glioblastoma and brain metastases from lung, breast and melanoma. Focused ultrasound with microbubbles transiently opens the barrier and has delivered chemotherapy and antibodies in early trials; receptor-mediated shuttles (transferrin receptor) carry biologics across in neurology. The proposal is a platform programme: standardised ultrasound protocols and devices, a library of shuttle-enabled versions of active cancer drugs (antibody-drug conjugates, checkpoint inhibitors, bispecifics), pharmacokinetic validation in humans, and a trial network to test them in brain tumours and metastases.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The brain: barrier and sanctuary): Stupp et al., Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma (NEJM 2005)","url":"https://doi.org/10.1056/NEJMoa043330"}],"tags":[],"related":[],"cancers":["glioblastoma","breast-her2-positive","nsclc","melanoma"],"sections":[],"technologies":["hifu-histotripsy","adc"],"targets":[],"drugs":[],"companies":["insightec"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-brain-delivery","b-metastasis-biology"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Platform-enabled delivery raises intratumoural drug concentrations at least fivefold and improves intracranial progression-free survival in at least two indications within eight years.","rationale":"Many drugs that work systemically fail intracranially for delivery, not biology; a solved delivery platform unlocks the existing armamentarium rather than requiring new drugs.","test":"Phase 1/2 studies with drug-level measurement in resected tissue after ultrasound or shuttle delivery, followed by randomised intracranial efficacy trials in HER2-positive breast cancer brain metastases and glioblastoma.","maturity":"early-clinical","actor":"research","cost":"large","horizonYears":8},{"id":"idea-tr2-rt-drug-platform","kind":"idea","name":"A standing platform for testing new drugs with radiotherapy","aka":[],"tldr":"Radiotherapy is given to half of all cancer patients but few new drugs are tested alongside it. A permanent trial platform would test drug-plus-radiation pairs systematically.","summary":"Radiosensitisers and immune-radiation combinations have strong biological rationale but almost no industry sponsorship because radiotherapy is unpatentable. The CONCORDE platform in the UK tests DNA-damage-response inhibitors with thoracic radiotherapy. Extending the model to a standing multi-tumour radiotherapy-drug platform with dose-finding modules and a shared radiotherapy quality-assurance backbone would fill a systematic gap.","asOf":"2026-09-08","links":[{"label":"CONCORDE platform (page moved; nearest live section)","url":"https://www.leedsth.nhs.uk/research/"}],"tags":[],"related":["nrg-oncology","cruk"],"cancers":["nsclc","head-and-neck","glioblastoma"],"sections":["radiation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-combination-space","b-surgery-radiation-innovation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A radiotherapy-drug platform will complete dose-finding for at least four novel agent-radiotherapy pairs per year, compared with fewer than one per year in the preceding decade across the same tumour types.","rationale":"Radiotherapy quality assurance and dose-finding are the expensive fixed costs; a platform amortises them across agents.","test":"Fund a three-tumour platform (lung, head and neck, glioma) with four initial drug modules; measure agents through dose-finding per year.","maturity":"early-clinical","actor":"research","cost":"large","horizonYears":5},{"id":"idea-tr1-standing-platform-per-cancer","kind":"idea","name":"A standing platform trial for every major cancer, funded as infrastructure","aka":[],"tldr":"Rather than building a new trial from scratch for every drug, keep one permanent trial open per cancer where new treatments can be slotted in and dropped out, sharing the same patients, control group and infrastructure.","summary":"Perpetual multi-arm platform trials with a common control, Bayesian adaptive randomisation and pre-agreed arm entry and graduation rules, as in I-SPY 2 (breast), STAMPEDE (prostate) and GBM AGILE (glioblastoma). The proposal is to fund the fixed infrastructure (governance, sites, data, statistics) for each of the ten commonest cancers as a public or philanthropic good, with sponsors paying a per-arm fee.","asOf":"2026-09-08","links":[{"label":"I-SPY Trials","url":"https://www.ispytrials.org/"},{"label":"STAMPEDE trial","url":"https://www.stampedetrial.org/"},{"label":"Global Coalition for Adaptive Research (GBM AGILE)","url":"https://www.gcaresearch.org/"}],"tags":[],"related":["prostate-roadmap","idea-prostate-randomise-the-sequence-not-only-the-drugs"],"cancers":["glioblastoma","prostate","pancreatic"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["basket-umbrella-platform"],"trials":[],"people":[],"bottlenecks":["b-trial-design","b-trial-enrolment","b-combination-space"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Platform-enrolled arms will reach a go/no-go decision at half the cost and time per arm of stand-alone phase 2 trials in the same indication, and the number of agents tested per year in each cancer will rise.","rationale":"Fixed costs dominate trial economics. Platforms have already shown faster and cheaper arm evaluation and produced approvals. What is missing is stable funding independent of any single sponsor.","test":"Fund two new disease platforms for five years and compare cost and time per arm and per approval-supporting result with contemporaneous stand-alone trials in the same indications.","maturity":"being-tested-at-scale","actor":"philanthropy","cost":"large","horizonYears":5},{"id":"idea-bio1-resistance-platform-trial","kind":"idea","name":"A standing platform trial that assigns treatment by how the tumour escaped","aka":[],"tldr":"Instead of a new trial for each resistance mechanism, one continuous trial could sort patients into arms based on the reason their last treatment failed.","summary":"A perpetual master protocol with a common progression-biopsy and plasma workup, a shared control arm and arms opened and closed as mechanisms and matched agents emerge. This shares infrastructure across sponsors, gives patients a reason to have the biopsy, and produces mechanism-specific efficacy estimates that no single-sponsor trial can. Precedents include Lung-MAP and I-SPY in other settings.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Acquired resistance to every therapy): Soria et al., Osimertinib in untreated EGFR-mutated NSCLC (FLAURA, NEJM 2018)","url":"https://doi.org/10.1056/NEJMoa1713137"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["cgp","liquid-biopsy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["basket-umbrella-platform"],"trials":[],"people":[],"bottlenecks":["b-resistance","b-trial-design","b-trial-enrolment"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A resistance platform enrols faster and produces mechanism-specific efficacy answers at lower cost per arm than separate single-mechanism trials, with a majority of enrolled patients receiving a matched agent.","rationale":"Resistance mechanisms are individually rare but collectively common, which is exactly the situation platform designs handle best; the workup requirement is the same for all arms.","test":"Launch with three arms in one disease area, and compare cost per randomised patient, time to first readout and screen-failure rate with matched standalone trials.","maturity":"speculative","actor":"research","cost":"large","horizonYears":6},{"id":"idea-bio2-n-of-1-framework","kind":"idea","name":"A standing rulebook for one-patient treatments","aka":[],"tldr":"Sometimes a treatment must be designed for a single patient. Agreeing in advance what evidence and safety checks are needed would make that fast, fair and learnable.","summary":"Bespoke antisense oligonucleotides and personalised gene therapies have been given to individual patients with ultra-rare disease under case-by-case regulatory arrangements, and regulators have begun issuing platform-oriented guidance. Oncology has the same need for bespoke neoantigen products, personalised oligonucleotides and unusual repurposing. A published framework (pre-agreed manufacturing standards, ethics route, mandatory registry submission and shared outcome reporting) would turn one-off heroics into cumulative knowledge.","asOf":"2026-09-08","links":[{"label":"FDA Oncology Center of Excellence (page moved; nearest live section)","url":"https://www.fda.gov/about-fda/"}],"tags":[],"related":["clinicaltrials-gov"],"cancers":[],"sections":[],"technologies":["antisense-sirna","neoantigen-mrna-vaccine","programmable-dna-targeting-therapeutics"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-rare-cancers","b-regulatory-fragmentation","b-negative-results"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A published n-of-1 oncology framework shortens the time from decision to treatment from over a year to under four months, and captures outcomes for over 80% of cases in a public registry.","rationale":"Rare disease neurology has already shown that bespoke therapy is technically feasible and that the binding constraint is regulatory and ethical process. Registry capture is what converts anecdotes into evidence, as it did for expanded access programmes that later informed approvals.","test":"One regulator publishes a draft framework and runs 20 cases through it, reporting time to treatment, safety events and completeness of registry capture.","maturity":"speculative","actor":"regulator","cost":"small","horizonYears":5},{"id":"idea-fund-non-drug-trial-quota","kind":"idea","name":"A statutory minimum share of public trial money for surgery and radiotherapy","aka":[],"tldr":"Surgery and radiotherapy cure more people than drugs but get a fraction of trial funding because there is no company sponsor. A rule would guarantee them a fixed share of public trial money.","summary":"Public trial funders (NCI's NCTN, NIHR, EU programmes) would set a floor, for example 25%, for trials whose primary intervention is surgical, radiotherapeutic, interventional or a care-pathway change. The floor is justified because private sponsors fund almost all drug phase 3s but essentially no non-drug ones, so public money should preferentially cover the market failure. The quota would be paired with core funding for surgical and radiotherapy trials units and quality assurance.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Funding follows fashion, not burden): Carter & Nguyen, A comparison of cancer burden and research spending (BMC Cancer 2012)","url":"https://doi.org/10.1186/1471-2407-12-526"}],"tags":[],"related":["idea-fund-surgical-trials-network","idea-fund-radiotherapy-trials-infrastructure"],"cancers":[],"sections":[],"technologies":["sbrt","robotic-surgery","imrt-igrt"],"targets":[],"drugs":[],"companies":["nrg-oncology","alliance-oncology"],"institutions":["the-christie","royal-marsden"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-funding-allocation","b-surgery-radiation-innovation"],"keyPapers":["paper-sun-bmc-cancer"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A 25% floor doubles the number of adequately powered randomised surgical and radiotherapy trials started per year within five years, without reducing the total number of practice-changing results per public dollar.","rationale":"Published audits show surgery and radiotherapy receive a small single-digit share of cancer research funding despite delivering around half of cures; where dedicated infrastructure exists (UK CTRad, TROG, the German Hodgkin Study Group) these fields have produced practice-changing trials at low cost.","test":"Audit one funder's portfolio by intervention type, apply the floor for one funding cycle, and count trials started, completed and practice-changing five years later against the prior cycle.","maturity":"speculative","actor":"policy","cost":"large","horizonYears":5},{"id":"idea-reg-generic-chemo-strategic-reserve","kind":"idea","name":"A strategic reserve of essential generic cancer drugs to end recurring shortages","aka":[],"tldr":"Cancer patients have had treatments delayed because basic chemotherapy drugs ran out. Keeping a national stockpile, like for flu antivirals, would prevent this.","summary":"Shortages of cisplatin, carboplatin, methotrexate, fluorouracil and other essential generics recur every few years in high-income countries and chronically in LMICs, usually after a single manufacturer's quality failure. Several countries hold strategic reserves of antivirals and antibiotics; none holds oncology essentials. The proposal is a rotating national or regional reserve covering six months of demand for the 20 most shortage-prone oncology generics, with stock rotated through normal supply chains to avoid waste, procurement rules that require dual sourcing, and automatic release triggers.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (No incentive to repurpose cheap drugs): Pantziarka et al., The Repurposing Drugs in Oncology (ReDO) Project (ecancer 2014)","url":"https://doi.org/10.3332/ecancer.2014.442"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["platinum"],"targets":[],"drugs":["carboplatin","paclitaxel"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-generic-repurposing","b-global-access"],"keyPapers":["paper-pantziarka-ecancermedicalscience"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Reserves eliminate treatment delays and dose modifications attributed to shortages of covered drugs and reduce shortage-related switching to inferior regimens to near zero.","rationale":"The drugs are cheap and stable, the shortage cost (delayed curative treatment) is very high, and the reserve approach has worked for other essential medicines; the barrier is only that no one has been made responsible.","test":"Establish a reserve for ten drugs in one country and compare shortage-related treatment delays with the prior three years and with peer countries.","maturity":"early-clinical","actor":"policy","cost":"medium","horizonYears":2},{"id":"idea-moon-treatment-refusal-pathway","kind":"idea","name":"A structured pathway for patients declining proven treatment","aka":[],"tldr":"When someone refuses recommended treatment, do not just record it. Offer a second conversation, address the beliefs behind it, keep the door open and track what happens.","summary":"Refusal of standard therapy is associated with markedly worse survival in observational studies, and many refusals reflect misinformation, fear of toxicity or distrust rather than settled values. The proposal is a standard pathway: a documented exploration of reasons, a second consultation with a different clinician or navigator, targeted information addressing the specific belief, an explicit offer to revisit at defined intervals, and registry tracking of refusals and outcomes.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Misinformation and unproven therapies): Johnson et al., Cancer misinformation and harmful information on Facebook and other social media (JNCI 2022)","url":"https://doi.org/10.1093/jnci/djab141"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-misinformation","b-patient-voice"],"keyPapers":["paper-johnson-j-natl-cancer-inst"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"The pathway converts a meaningful share of initial refusals into informed acceptance or safer alternatives and improves survival among initial refusers compared with historical controls.","rationale":"Refusal is often a moment of fear rather than a fixed decision; systems currently treat it as final.","test":"Implement in three centres; compare rates of eventual treatment acceptance and 2-year survival among initial refusers against matched historical cohorts.","maturity":"early-clinical","actor":"clinic","cost":"small","horizonYears":2},{"id":"idea-data-off-label-outcomes-registry","kind":"idea","name":"A structured registry for every off-label cancer drug use","aka":[],"tldr":"Doctors often use cancer drugs outside their approved use based on a hunch or a small study. Record what happens every time so the hunches become evidence.","summary":"Off-label use is common in oncology, especially for rare tumours and molecularly matched therapy, and the outcomes are almost never captured. DRUP (Netherlands) and TAPUR (ASCO) showed that a pragmatic protocol can turn off-label use into evidence and even into reimbursement (DRUP's personalised reimbursement model). The proposal extends this to all off-label anticancer use: a light-touch registration with structured indication, biomarker and outcome capture as a condition of reimbursement.","asOf":"2026-09-08","links":[{"label":"DRUP trial (archived copy)","url":"https://web.archive.org/web/20140517065619/http://drup.nl/"},{"label":"ASCO TAPUR","url":"https://www.tapur.org/"}],"tags":[],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["asco","nki"],"pathways":[],"terms":["real-world-evidence","tumour-agnostic"],"trials":[],"people":[],"bottlenecks":["b-real-world-evidence","b-generic-repurposing","b-rare-cancers"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"An off-label registry will generate evidence supporting reimbursement or label expansion for at least five drug-indication pairs within four years, and will identify at least as many with no benefit that should stop being used.","rationale":"DRUP identified active cohorts (for example, nivolumab in dMMR tumours) and led to conditional reimbursement; the model has worked but only for molecularly selected patients in a few countries.","test":"Implement registration-as-condition-of-reimbursement for off-label targeted and immune therapies in one national payer; report cohorts reaching the pre-specified efficacy threshold at 24 months.","maturity":"early-clinical","actor":"payer","cost":"medium","horizonYears":3},{"id":"idea-acc-survivor-biobank-late-effect-prediction","kind":"idea","name":"A survivor biobank to find who will develop late effects before they do","aka":[],"tldr":"Two people can have identical treatment and only one develops heart failure or a second cancer years later. Collecting blood and genetic data from survivors could reveal who is at risk and who can be reassured.","summary":"Genetic variants (for instance in anthracycline cardiotoxicity), clonal haematopoiesis, and circulating biomarkers may predict late effects, but studies are small and scattered. A prospective survivor biobank with baseline and serial samples linked to treatment exposures and long-term outcomes would allow discovery and validation of predictive markers, enabling risk-adapted surveillance and preventive therapy.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Survivorship and late effects are neglected): NCI Office of Cancer Survivorship statistics","url":"https://cancercontrol.cancer.gov/ocs/statistics"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["cardio-oncology","germline-testing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-biomarker-validation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Within six years the biobank will validate at least one biomarker or polygenic score that stratifies late cardiotoxicity or second-cancer risk with sufficient discrimination to change surveillance intensity.","rationale":"Pharmacogenomic predictors of toxicity have been found where cohorts were large enough; late effects have never had such a resource.","test":"Enrol 20,000 survivors with samples at end of treatment and five years, linked to registry outcomes, with pre-registered discovery and validation analyses.","maturity":"speculative","actor":"research","cost":"medium","horizonYears":6},{"id":"idea-acc-aya-survivorship-passport","kind":"idea","name":"A survivorship passport app for adolescent and young adult survivors","aka":[],"tldr":"Adolescent and young adult survivors live longest with late effects and are the group most often lost to follow-up as they change doctors over decades. A phone app version of Europe's Survivorship Passport, holding treatment history, exposure-based risk explanations and screening reminders, would travel with them for life.","summary":"Adolescent and young adult survivors are the group most likely to be lost to follow-up and to face late effects for the longest. The European SurPass (Survivorship Passport) initiative has developed a standardised electronic passport with treatment summary and individualised follow-up recommendations; adoption is uneven. A patient-held app version with reminders, exposure-based risk explanations, and a shareable summary would improve long-term adherence.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Survivorship and late effects are neglected): NCI Office of Cancer Survivorship statistics","url":"https://cancercontrol.cancer.gov/ocs/statistics"}],"tags":[],"related":["idea-acc-portable-treatment-summary"],"cancers":["hodgkin-lymphoma","all-leukemia","sarcoma","aya-cancers"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-patient-voice"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Survivors using the passport app will show at least 30% higher adherence to recommended long-term surveillance at five years than those with a paper summary or none.","rationale":"Patient-held records improve engagement when the patient is the constant across many providers; young people are the population most reachable through a phone.","test":"A randomised trial in 1,000 AYA survivors at end of treatment with surveillance adherence, self-reported knowledge of risks, and health-service contact as endpoints.","maturity":"early-clinical","actor":"patients","cost":"small","horizonYears":2},{"id":"idea-fund-survivorship-endowment-levy","kind":"idea","name":"A survivorship research endowment funded by a levy on curative therapy prices","aka":[],"tldr":"Tens of millions of people live after cancer with heart damage, infertility and second cancers. A tiny levy on the price of curative treatments would build a permanent fund to study and treat late effects.","summary":"Health systems and payers negotiate a 0.5% levy on reimbursed prices of curative-intent oncology drugs and radiotherapy into an independent endowment for late-effects research and survivorship services: long-term cohort follow-up, cardio-oncology and fertility-preservation trials, second-cancer surveillance and return-to-work interventions. The logic is that the cost of cure includes the cost of living with its consequences, and that no manufacturer has an incentive to fund it.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Funding follows fashion, not burden): Carter & Nguyen, A comparison of cancer burden and research spending (BMC Cancer 2012)","url":"https://doi.org/10.1186/1471-2407-12-526"}],"tags":[],"related":["idea-exercise-as-adjuvant"],"cancers":["hodgkin-lymphoma","all-leukemia","breast-hr-positive"],"sections":[],"technologies":["cardio-oncology","exercise-oncology"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-funding-allocation","b-survivorship"],"keyPapers":["paper-sun-bmc-cancer"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"An endowment of this kind funds long-term cohort follow-up for more than 80% of paediatric and young-adult survivors in its jurisdiction within five years and produces at least three practice-changing late-effects interventions within ten.","rationale":"Earmarked levies have built sustainable research funds elsewhere: France's tobacco tax allocation, the US vaccine injury compensation excise tax, and blood-product and pharmaceutical sector levies in several European countries. Survivorship research currently competes poorly in general peer review because it lacks novelty appeal.","test":"Model the levy yield against reimbursed spend in one country, then negotiate a three-year pilot with one national payer and one manufacturer group, tracking funded cohort coverage and cost.","maturity":"speculative","actor":"payer","cost":"large","horizonYears":5},{"id":"idea-prev-capsule-sponge-pharmacy","kind":"idea","name":"A swallowable sponge test for reflux patients, offered in pharmacies","aka":[],"tldr":"A pill on a string collects cells from the food pipe and finds Barrett's oesophagus, a precursor of cancer. Offering it in pharmacies to people on long-term heartburn drugs would find it early.","summary":"The capsule sponge (Cytosponge-TFF3) increased Barrett's detection ten-fold in primary care in BEST3; BEST4 tests screening and surveillance. Propose delivery through community pharmacies for patients on chronic acid suppression, with nurse-administered sponge, a central laboratory, and AI-assisted pathology.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The hardest cancers are found late): Crosby et al., Early detection of cancer (Science 2022)","url":"https://doi.org/10.1126/science.aay9040"}],"tags":[],"related":[],"cancers":["esophageal"],"sections":["early-detection"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["cruk"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-early-detection","b-prevention-adoption"],"keyPapers":["paper-crosby-science"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Pharmacy-based capsule sponge screening achieves at least 40% uptake in eligible reflux patients and detects dysplastic Barrett's at three times the rate of usual care, reducing stage III-IV oesophageal adenocarcinoma at five years.","rationale":"Precursor detection plus endoscopic ablation is curative; the bottleneck is reaching the population, not the test.","test":"Cluster-randomised pharmacy pilot in one region (50 pharmacies).","maturity":"being-tested-at-scale","actor":"clinic","cost":"medium","horizonYears":5},{"id":"idea-moon-synthetic-lethality-map-every-driver","kind":"idea","name":"A synthetic lethality map for every cancer driver in every tissue context","aka":[],"tldr":"For each cancer-causing mutation, find every gene the cancer cell newly depends on, in every tissue, so that even undruggable drivers get druggable partners.","summary":"PARP inhibitors in BRCA-mutant cancers proved synthetic lethality can be turned into medicine; DepMap has screened around two thousand cell lines but coverage of driver-context combinations, in vivo dependencies and combination interactions is incomplete. The proposal is a systematic programme: isogenic and patient-derived models for each of the roughly 100 recurrent drivers across major tissue contexts, genome-wide CRISPR knockout, activation and base-editing screens in vitro and in vivo (including immune-competent settings), and drug-combination anchor screens, released openly with a standardised dependency confidence score.","asOf":"2026-09-08","links":[{"label":"DepMap","url":"https://depmap.org/portal/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["crispr-screens","synthetic-lethality-approaches","organoids","pdx-models"],"targets":["tp53","kras","parp"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["synthetic-lethality"],"trials":[],"people":[],"bottlenecks":["b-undruggable-targets","b-resistance"],"keyPapers":["paper-vogelstein-surfing-p53-network-nature-2000"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"The map yields at least twenty validated context-specific dependencies for drivers currently considered undruggable (MYC, mutant TP53 loss, SMARCA4, ARID1A) that translate into clinical programmes within a decade.","rationale":"Dependencies are context-dependent and rarely visible in a single model; systematic coverage is what made the BRCA-PARP relationship exploitable, and screening cost has fallen by orders of magnitude.","test":"Fund the first 20 driver-context pairs; success is prospective validation of at least three new dependencies in patient-derived models with drug-like inhibitors.","maturity":"preclinical-evidence","actor":"research","cost":"large","horizonYears":5},{"id":"idea-data-synthetic-companion-datasets","kind":"idea","name":"A synthetic twin of every restricted cancer dataset for code development","aka":[],"tldr":"Publish a fake but realistic copy of each secure cancer dataset so researchers can write and test their code at home, then run the finished code on the real data.","summary":"Access to secure datasets typically takes months; analysts then waste TRE time debugging. Synthetic datasets with the same schema and approximate joint distributions (for example the Simulacrum, built from the English cancer registry by Health Data Insight) let code be written and unit-tested outside the enclave. The proposal makes a validated synthetic companion mandatory for every dataset in a national cancer data space, with fidelity and privacy metrics published.","asOf":"2026-09-08","links":[{"label":"The Simulacrum (Health Data Insight)","url":"https://simulacrum.healthdatainsight.org.uk/"}],"tags":[],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-data-silos"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Providing a synthetic companion dataset will reduce median secure-environment compute time per project by a third and the number of failed code submissions by half.","rationale":"The Simulacrum has been used to develop analyses that later ran unchanged on real registry data; the pattern is proven but not systematic.","test":"Measure TRE time and code-failure rate for projects with and without access to a synthetic companion in one national TRE over 18 months.","maturity":"early-clinical","actor":"data","cost":"small","horizonYears":2},{"id":"idea-tr2-target-failure-index","kind":"idea","name":"A target de-risking index that counts failures as well as successes","aka":[],"tldr":"For each drug target, show how many programmes have been tried against it and how many failed, so new teams know what they are up against.","summary":"Target prioritisation platforms (Open Targets) weight positive evidence. A complementary index that aggregates discontinued programmes, failed trials and deposited negative preclinical results per target and indication, with reasons where known, would give a Bayesian prior: a target with eight failed programmes and no success should require a stronger hypothesis than one never tried. Publicly available pipeline data makes a first version feasible now.","asOf":"2026-09-08","links":[{"label":"Open Targets","url":"https://platform.opentargets.org/"}],"tags":[],"related":["open-targets","idea-tr2-failure-taxonomy","idea-tr2-preclinical-negative-registry"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-negative-results","b-undruggable-targets"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Targets in the highest-failure decile will continue to attract new programmes at the same rate as others unless the index is visible; where visible, new programme starts against them will fall by at least a quarter unless accompanied by a new mechanistic rationale.","rationale":"Herding on a few targets (IDO1, CD47, TIGIT) with repeated failure is a documented pattern. Making the failure count visible changes the decision calculus.","test":"Build the index for 300 oncology targets from public pipeline and trial data; publish; track new programme initiations by index decile over three years.","maturity":"speculative","actor":"data","cost":"small","horizonYears":2},{"id":"idea-prev-lmic-five-cancer-methylation-test","kind":"idea","name":"A ten-dollar blood test for the five cancers that kill most people in poorer countries","aka":[],"tldr":"Most cancer deaths are in low and middle income countries, where scans and endoscopies are scarce. A cheap methylation blood test tuned to liver, stomach, oesophageal, cervical and breast cancer could fill the gap.","summary":"Most cancer deaths occur in low and middle income countries where scans and endoscopies are scarce, so this idea develops a narrow-panel targeted-methylation blood test, run on low-cost sequencing or PCR, tuned to liver, stomach, oesophageal, cervical and breast cancer at a marginal cost of around ten dollars. Current MCEDs cost far more and target the US cancer mix; narrowing the target set and using PCR cuts cost, and liver and gastric cancers shed methylated DNA relatively well. A positive result would lead to ultrasound or endoscopy. The test is case-control development then a prospective 20,000-person cohort in a high-incidence region, with IARC as a partner. Speculative in maturity, it addresses The hardest cancers are found late and Most of the world has almost no cancer care.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The hardest cancers are found late): Crosby et al., Early detection of cancer (Science 2022)","url":"https://doi.org/10.1126/science.aay9040"}],"tags":[],"related":[],"cancers":["hcc","gastric","esophageal","cervical"],"sections":["early-detection"],"technologies":["mced","methylation-profiling"],"targets":[],"drugs":[],"companies":[],"institutions":["iarc"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-early-detection","b-global-access"],"keyPapers":["paper-crosby-science"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A five-cancer assay with marginal cost of $10 or less achieves at least 60% stage I-II sensitivity for liver, gastric and oesophageal cancer at 99% specificity, and is cost-effective at LMIC thresholds.","rationale":"Narrowing the target set and using PCR rather than deep sequencing sharply cuts cost; liver and gastric cancers shed methylated DNA relatively well.","test":"Case-control development, then a prospective 20,000-person cohort in a high-incidence region.","maturity":"speculative","actor":"philanthropy","cost":"medium","horizonYears":6},{"id":"idea-prev-incidentaloma-natural-history-cohort","kind":"idea","name":"A ten-year cohort of incidental findings to calibrate follow-up guidelines","aka":[],"tldr":"Scans find unexpected lumps in the adrenal, thyroid, pancreas and lung. Nobody knows how many matter. A national cohort following them for ten years would tell us whom to watch.","summary":"Scans find unexpected lumps in the adrenal, thyroid, pancreas and lung, and nobody knows how many matter, so this idea enrols every incidental finding flagged by structured radiology reporting into a national linked cohort followed for ten years. Incidentaloma guidelines rest on small retrospective series; natural history data is the missing evidence, and structured reporting makes capture feasible. The cohort would estimate cancer risk by lesion type, size and patient factors and allow follow-up recommendations to be pruned where risk is very low. The test is enrolment in a national health system with interim analyses at three and five years. Speculative in maturity, it addresses the bottlenecks Overdiagnosis and false alarms and Weak real-world evidence and registries.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Overdiagnosis and false alarms): Welch & Black, Overdiagnosis in cancer (JNCI 2010)","url":"https://doi.org/10.1093/jnci/djq099"}],"tags":[],"related":[],"cancers":[],"sections":["early-detection","imaging"],"technologies":["ct","mri"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-overdiagnosis","b-real-world-evidence"],"keyPapers":["paper-welch-j-natl-cancer-inst"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"For at least three common incidentaloma categories, ten-year cancer risk is low enough (under 1%) that current follow-up recommendations can be dropped, reducing follow-up imaging by at least 30%.","rationale":"Natural history data is the missing evidence; structured reporting makes capture feasible.","test":"Enrol via structured reporting in a national health system; interim analyses at three and five years.","maturity":"speculative","actor":"data","cost":"medium","horizonYears":5},{"id":"idea-bio2-oligometastatic-signature","kind":"idea","name":"A test to tell true oligometastatic disease from hidden widespread spread","aka":[],"tldr":"Some people have only a few sites of spread and can be treated at each one; others have further deposits not yet visible, and counting lesions cannot tell them apart. A signature built from tumour DNA levels, microRNA classifiers and clonal diversity across lesions would define the biology and spare futile ablation.","summary":"Ablative treatment of all visible lesions improves survival in selected patients, but selection today is anatomical and therefore crude. Candidate discriminators include ctDNA level and clearance kinetics, microRNA classifiers reported in oligometastatic lung cancer, and clonal diversity across lesions. A locked signature, prospectively validated, would define the biology rather than the lesion count.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Metastasis is understood least and studied last): Dillekås et al., Are 90% of deaths from cancer caused by metastases? (Cancer Medicine 2019)","url":"https://doi.org/10.1002/cam4.2474"}],"tags":[],"related":["idea-psma-pet-guided-mdt"],"cancers":["nsclc","prostate","colorectal"],"sections":[],"technologies":["sbrt","mrd-testing","liquid-biopsy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["oligometastatic","oligoprogression","ctdna"],"trials":[],"people":[],"bottlenecks":["b-metastasis-biology","b-biomarker-validation"],"keyPapers":["paper-dillekas-cancer-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A combined ctDNA-kinetic and transcriptomic signature identifies patients whose disease is genuinely restricted, in whom total metastasis-directed ablation gives two-year progression-free survival above 50%, against below 20% in signature-negative patients.","rationale":"The benefit of metastasis-directed therapy varies enormously and unpredictably, which is the signature of a mixed population. Analogous molecular refinement transformed adjuvant chemotherapy decisions in breast cancer through genomic assays.","test":"Embed a locked biomarker panel in an ongoing metastasis-directed radiotherapy trial with a pre-specified interaction analysis; a null interaction kills the signature cheaply.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":5},{"id":"idea-prev-therapeutic-hpv-vaccine-cin","kind":"idea","name":"A therapeutic vaccine to clear cervical precancer without surgery","aka":[],"tldr":"Precancer is treated by cutting away part of the cervix, which raises pregnancy risks. A vaccine that makes the immune system clear the infected cells would avoid surgery.","summary":"Cervical precancer is treated by cutting away part of the cervix, which raises pregnancy risks, so this idea develops next-generation therapeutic vaccines, mRNA or E6/E7-targeted, that make the immune system clear CIN2/3 lesions, aimed first at women planning pregnancy. HPV oncoproteins are foreign antigens present in every lesion cell, and DNA vaccines such as VGX-3100 have already shown partial efficacy. Endpoints would be histological regression and HPV clearance at six months, allowing surgery to be avoided. The test is a phase 2b RCT of 400 women with a regression endpoint. At early-clinical maturity it addresses the bottlenecks Prevention we already have is not deployed and Overdiagnosis and false alarms, and relates to Cancer interception vaccines for high-risk carriers.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Prevention we already have is not deployed): Islami et al., Proportion of cancer attributable to modifiable risk factors (CA 2018)","url":"https://doi.org/10.3322/caac.21440"}],"tags":[],"related":["idea-interception-vaccines"],"cancers":["cervical"],"sections":["prevention","immunotherapy"],"technologies":["hpv-vaccine"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption","b-overdiagnosis"],"keyPapers":["paper-islami-ca-cancer-j-clin"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A therapeutic HPV vaccine achieves at least 50% histological regression with viral clearance at six months in CIN2/3, allowing surgery to be avoided in half of treated women.","rationale":"HPV oncoproteins are foreign antigens present in every lesion cell, and partial efficacy is already proven.","test":"Run a phase 2b RCT of 400 women with a regression endpoint.","maturity":"early-clinical","actor":"industry","cost":"medium","horizonYears":5},{"id":"idea-fund-device-and-technique-translation-fund","kind":"idea","name":"A translation fund for academic surgical devices and radiotherapy technology","aka":[],"tldr":"New surgical tools, imaging probes and radiotherapy hardware invented in universities rarely attract investors. A dedicated fund would pay for prototyping, safety testing and first-in-human studies.","summary":"A fund for academic devices and techniques in cancer surgery and radiotherapy: intraoperative imaging probes, margin-assessment tools, low-cost brachytherapy applicators, FLASH-capable beam systems, adaptive planning software, robotic instruments. It pays for design-for-manufacture, ISO 13485 quality systems, biocompatibility and safety testing and IDEAL-framework early studies. Device venture capital is thin outside cardiology and orthopaedics, and academic engineering groups have no path to first-in-human without it. The fund would work with translational institutes and the surgical and radiotherapy trials networks proposed elsewhere in this wave.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The valley of death between lab and product): Butler, Translational research: crossing the valley of death (Nature 2008)","url":"https://doi.org/10.1038/453840a"}],"tags":[],"related":["idea-fund-surgical-trials-network","idea-fund-device-technique-registry","idea-fund-intraoperative-imaging-trials"],"cancers":[],"sections":[],"technologies":["fluorescence-guided-surgery","optical-imaging","flash-rt","mr-linac","brachytherapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-translational-valley","b-surgery-radiation-innovation"],"keyPapers":["paper-butler-nature"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A device translation fund of $50 million over five years brings at least fifteen academic cancer surgery or radiotherapy technologies to first-in-human evaluation and at least five to a randomised or IDEAL stage 3 study, compared with a handful in the preceding five years.","rationale":"Fluorescence-guided surgery agents and intraoperative margin tools have taken well over a decade to reach approval largely for lack of translational funding; where public funding existed (for example the UK's NIHR i4i programme) academic devices reached patients. Oncology devices are a market failure because they are hard to patent broadly and slow to reimburse.","test":"Fund a first cohort of ten technologies and track time to first-in-human, regulatory milestones and subsequent trials against a matched set of unfunded academic devices.","maturity":"speculative","actor":"philanthropy","cost":"medium","horizonYears":4},{"id":"idea-prev-glp1-cancer-prevention-rct","kind":"idea","name":"A trial of GLP-1 weight-loss drugs with cancer as the primary outcome","aka":[],"tldr":"Obesity raises the risk of 13 cancers, and GLP-1 weight-loss drugs are already in routine use for diabetes and obesity. Observational data hint that they cut obesity-related cancers but confounding is severe, so a randomised trial in adults aged 50 to 70 with a BMI of 30 or more should make cancer the primary outcome.","summary":"Observational data suggest GLP-1 receptor agonists reduce obesity-related cancer incidence, but confounding is severe. Propose an RCT, or prospective cancer adjudication embedded in ongoing cardiovascular outcome trials, with incident obesity-related cancer as the primary endpoint in adults aged 50-70 with BMI of 30 or more.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Prevention we already have is not deployed): Islami et al., Proportion of cancer attributable to modifiable risk factors (CA 2018)","url":"https://doi.org/10.3322/caac.21440"}],"tags":[],"related":[],"cancers":["endometrial","colorectal","pancreatic","hcc"],"sections":["prevention"],"technologies":["chemoprevention"],"targets":[],"drugs":[],"companies":["eli-lilly"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption"],"keyPapers":["paper-islami-ca-cancer-j-clin"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"GLP-1 receptor agonist therapy reduces incidence of obesity-related cancers by at least 20% over seven years.","rationale":"Bariatric surgery reduces cancer incidence in cohort studies; pharmacological weight loss may reproduce this through insulin/IGF and inflammatory pathways.","test":"Run a 20,000-person RCT or a pooled analysis of cardiovascular outcome trials with prospective cancer adjudication.","maturity":"early-clinical","actor":"industry","cost":"large","horizonYears":8},{"id":"idea-gbc-t2a-spare-liver-resection-trial","kind":"idea","name":"A trial of sparing the liver resection in peritoneal-side (T2a) gallbladder cancer","aka":[],"tldr":"Muscle-invading gallbladder tumours on the free side of the organ recur in the liver far less often than those against it. Two meta-analyses found the liver resection helped only the liver-side group, so a randomised trial could test dropping it for the free side.","summary":"Shindoh (2015) showed liver recurrence of 3 percent for peritoneal-side against 23 percent for hepatic-side T2 tumours; Kang's meta-analysis (1,789 patients) found no survival difference between extended and simple cholecystectomy in T2a (odds ratio 0.802) and Khan's (2,345 patients) found liver resection improved survival only in T2b. Lymphadenectomy would be retained because T2a nodal metastasis is still 27 percent. Reproducible assignment of side on pathology is the practical obstacle and would need a central review protocol.","asOf":"2026-09-24","links":[{"label":"Kang et al.: prognostic significance of tumour location in T2 gallbladder cancer, meta-analysis (J Clin Med 2021)","url":"https://europepmc.org/article/MED/34362101"},{"label":"Khan et al.: tumour location and liver resection in T2 gallbladder cancer, meta-analysis (Updates Surg 2021)","url":"https://europepmc.org/article/MED/34426958"}],"tags":["gallbladder-evidence"],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["t2a-versus-t2b","radical-cholecystectomy","lymphadenectomy","de-escalation"],"trials":[],"people":[],"bottlenecks":["b-surgery-radiation-innovation","b-trial-design"],"keyPapers":["paper-shindoh-t2-gallbladder-cancer-tumour-location-ann-surg-2015","paper-kang-t2-gallbladder-cancer-location-meta-analysis-jcm-2021","paper-khan-t2-gallbladder-cancer-liver-resection-meta-analysis-updates-surg-2021","paper-lee-t2-gallbladder-cancer-surgical-strategy-aso-2015"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"In T2a gallbladder cancer, cholecystectomy with portal lymphadenectomy but without liver bed resection is non-inferior to extended cholecystectomy for five-year recurrence-free survival.","rationale":"The liver bed is the target of the resection and the liver is rarely the site of recurrence in T2a; nodes remain a risk and are retained in the experimental arm.","test":"Randomised non-inferiority trial with central pathology confirmation of side, stratified by incidental versus suspected presentation; recurrence-free survival primary, liver-specific recurrence and morbidity secondary.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":8},{"id":"idea-fund-older-patients-trial-fund","kind":"idea","name":"A trials fund reserved for older and multimorbid patients","aka":[],"tldr":"Most people with cancer are over 65, but most trial patients are younger and fitter. A dedicated fund would pay for trials designed for the patients we actually treat.","summary":"Public and charitable funders create a standing fund for trials with inclusive eligibility (age, kidney function, performance status, comorbidity), geriatric assessment-guided dosing, and endpoints that matter to older adults (function, independence, time at home). Trials would test dose reductions, shorter courses and de-escalation of standard regimens in patients over 70, where retrospective data suggest toxicity and discontinuation are far higher than in trials. Industry has little incentive to run these because they mostly test less drug.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Funding follows fashion, not burden): Carter & Nguyen, A comparison of cancer burden and research spending (BMC Cancer 2012)","url":"https://doi.org/10.1186/1471-2407-12-526"}],"tags":[],"related":["idea-fund-payer-funded-pragmatic-trials","idea-fund-implementation-quota"],"cancers":[],"sections":[],"technologies":["geriatric-assessment"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-funding-allocation","b-aging-comorbidity","b-trial-diversity"],"keyPapers":["paper-sun-bmc-cancer"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A dedicated fund produces at least five phase 3 results in older adults within eight years that change guideline dosing or regimen choice, and increases the median trial age in the funder's portfolio by at least five years.","rationale":"The GAP70+ and GAIN trials showed geriatric assessment reduces toxicity; French GERICO and UK trials demonstrated feasibility of elderly-specific phase 3s. The gap is sustained funding, not method.","test":"Launch the fund for one cycle and compare median participant age, toxicity-driven discontinuation and guideline impact with the funder's general trials portfolio.","maturity":"speculative","actor":"policy","cost":"medium","horizonYears":4},{"id":"idea-data-tumour-board-evidence-assistant","kind":"idea","name":"A tumour board assistant that cites its evidence and tracks outcomes","aka":[],"tldr":"Give every tumour board a tool that pulls up the relevant trials and guideline lines for each case with citations, records what was decided, and later shows how the patient did.","summary":"Molecular tumour boards spend much of their time on literature search and produce recommendations that are rarely tracked to outcomes. The proposal is an assistant built on the evidence graph and computable guidelines: it prepares a cited evidence brief per case, records the board's recommendation in structured form, and links it to the patient's subsequent treatment and outcome, creating a learning loop across boards. Precedents include MSK's OncoKB-driven annotation and academic MTB decision-support pilots.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Knowledge reaches practice too slowly): Morris, Wooding & Grant, The answer is 17 years, what is the question (JRSM 2011)","url":"https://doi.org/10.1258/jrsm.2011.110180"}],"tags":[],"related":["oncokb","idea-data-provenance-first-decision-support"],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["mskcc"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-knowledge-diffusion","b-real-world-evidence"],"keyPapers":["paper-morris-j-r-soc-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Boards using the assistant will spend less time per case, reach recommendations more concordant with current guidelines, and will generate an outcome-linked dataset that reveals which recommendation types improve survival.","rationale":"Studies of tumour boards show variable concordance with guidelines and almost no outcome feedback; the missing ingredients are retrieval and structured recording, both now tractable.","test":"Deploy at five boards for one year; measure preparation time, guideline concordance, and completeness of outcome linkage versus the prior year.","maturity":"early-clinical","actor":"clinic","cost":"small","horizonYears":2},{"id":"idea-tnbc-uk-trial-access-and-germline-testing-audit","kind":"idea","name":"A UK audit of trial access and germline testing uptake in triple-negative breast cancer","aka":[],"tldr":"Every triple-negative patient under 60 in the UK should be offered a BRCA test at diagnosis because the result now changes treatment, and many should be offered a trial, but no one publishes how many are. A national audit through existing cancer registration and genomic laboratory data would show the gap by region before anyone tries to close it.","summary":"The UK and NHS page for triple-negative breast cancer names the specific referral, testing and funding gaps; this idea holds the published evidence behind an audit. What exists now: the OlympiA six-year update makes germline status a treatment decision with a survival benefit (hazard ratio 0.72); Atchley's series shows a triple-negative diagnosis itself predicts a BRCA1 variant in 57 percent of carriers; the ASCO, ASTRO and SSO guideline and NICE criteria both support testing at diagnosis; the POSH cohort shows the UK can assemble national young-onset breast cancer data with ethnicity and outcome. What is missing is a published figure for the proportion of eligible triple-negative patients tested within the neoadjuvant window, when the result can change surgery and adjuvant therapy, and for the proportion offered a trial, by region and ethnicity.","asOf":"2026-09-24","links":[{"label":"OlympiA six-year update (Ann Oncol 2026)","url":"https://europepmc.org/article/MED/42636977"},{"label":"Atchley et al.: BRCA status and triple-negative breast cancer (J Clin Oncol 2008)","url":"https://europepmc.org/article/MED/18779615"}],"tags":["tnbc-evidence"],"related":["idea-tnbc-disparities-in-access-and-outcomes"],"cancers":["tnbc"],"sections":[],"technologies":["germline-testing"],"targets":["brca"],"drugs":["olaparib"],"companies":[],"institutions":["nice","cruk"],"pathways":[],"terms":["germline-testing"],"trials":["olympia"],"people":[],"bottlenecks":["b-hereditary-risk","b-care-fragmentation","b-data-silos"],"keyPapers":["paper-olympia-6-year-update-ann-oncol-2026","paper-atchley-brca-status-triple-negative-jco-2008","paper-asco-hereditary-breast-cancer-guideline-jco-2020","paper-copson-posh-ethnicity-young-breast-cancer-uk-bjc-2014"],"journals":[],"dependsOn":[],"notes":["The UK and NHS page for triple-negative breast cancer records the gaps this audit would measure: no published rate of germline testing within the neoadjuvant window, no published trial-offer rate, and NHS England pages that could not be read on 24 September 2026."],"hypothesis":"Linking cancer registration, genomic laboratory hub and trial recruitment records will show that fewer than 60 percent of eligible triple-negative patients in England are germline tested before surgery and that testing and trial offers vary more than twofold between regions, and publishing the figures annually will raise both within two years.","rationale":"Audit and publication is the cheapest lever the NHS has, and for triple-negative disease the test result carries a proven survival benefit and the trials carry the new standards of care.","test":"Retrospective linkage for the 2023 to 2025 diagnostic cohort, then annual publication of tested-before-surgery and trial-offer rates by cancer alliance and ethnicity, with a target and a named owner.","maturity":"speculative","actor":"data","cost":"small","horizonYears":2},{"id":"idea-fund-universal-mta-fast-lane","kind":"idea","name":"A universal material transfer agreement with a thirty-day default","aka":[],"tldr":"Getting a cell line, mouse model or antibody from another lab can take six months of paperwork. Funders would require a standard agreement that goes through automatically unless someone objects within thirty days.","summary":"Funders and journals require that materials generated with their support are shared under the Uniform Biological Material Transfer Agreement or an equivalent open template (for example the OpenMTA for tool reagents), with institutions committing to a thirty-day default-approve process for non-commercial requests and to deposit the most requested reagents in repositories (Addgene, ATCC, JAX, EurOPDX). Material access delays are a documented cause of failed replications and slow translation; the fix is procedural, not scientific, and costs almost nothing.","asOf":"2026-09-08","links":[{"label":"Addgene","url":"https://www.addgene.org/"},{"label":"OpenMTA","url":"https://openmta.org/"}],"tags":[],"related":["cancer-models","idea-fund-standard-combination-agreement","idea-fund-academic-promotion-reform"],"cancers":[],"sections":[],"technologies":["pdx-models","organoids"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-ip-collaboration","b-reproducibility"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Funder-mandated standard MTAs reduce median time from request to receipt of research materials at participating institutions from months to under thirty days and increase the deposit rate of published reagents in public repositories above 80% within two years.","rationale":"Addgene shows that repository deposit with standard terms makes sharing near-frictionless for plasmids; the UBMTA has existed since 1995 but is undermined by institutional insistence on bespoke terms. Funder mandates worked for data sharing and open access.","test":"Two funders adopt the mandate for one year; survey request-to-receipt times and repository deposit rates at grantee institutions before and after.","maturity":"speculative","actor":"policy","cost":"small","horizonYears":1},{"id":"idea-fund-academic-radiopharma-pipeline","kind":"idea","name":"A university cyclotron network with shared regulatory files for new tracers","aka":[],"tldr":"Most new cancer imaging agents and radioactive drugs start in university hospitals. A network sharing production, quality files and regulatory paperwork would get them into multi-centre trials years faster.","summary":"Academic radiopharmacy has repeatedly produced the agents the field now runs on (PSMA ligands and FAPI tracers from Heidelberg, DOTATATE from Basel and Rotterdam) but each centre re-creates production, quality control and regulatory documentation. A funded network of university cyclotrons and radiopharmacies would share drug master files, validated synthesis modules, GMP quality systems and a common clinical trial application template, so a tracer validated in one centre can be adopted in ten within months. It would also provide isotope purchasing at scale (gallium-68 generators, lutetium-177, actinium-225 allocation) for academic trials.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The valley of death between lab and product): Butler, Translational research: crossing the valley of death (Nature 2008)","url":"https://doi.org/10.1038/453840a"}],"tags":[],"related":["idea-fund-phase-zero-fund","idea-fap-theranostics-pancancer","radiopharma-roadmap"],"cancers":[],"sections":[],"technologies":["psma-pet","fapi-pet","radioligand-therapy","targeted-alpha-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":["heidelberg-nct","dkfz","peter-mac"],"pathways":[],"terms":[],"trials":[],"people":["uwe-haberkorn","frederik-giesel","hofman-michael"],"bottlenecks":["b-translational-valley","b-manufacturing-cell-therapy"],"keyPapers":["paper-butler-nature"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A shared network reduces the time from first-in-human of an academic tracer or radioligand to a five-centre trial from the current several years to under eighteen months, and doubles the number of academic radiopharmaceuticals entering multi-centre trials within four years.","rationale":"PSMA PET spread globally because academic centres shared precursors and methods informally; formalising that with shared regulatory files removes the largest delay. Germany's and the Netherlands' academic radiopharmacy networks demonstrate feasibility within a country.","test":"Fund a ten-centre network with a shared master file for two agents and measure time to multi-centre trial start and centres activated compared with agents developed without the network.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":4},{"id":"idea-prev-urine-dna-haematuria-triage","kind":"idea","name":"A urine DNA test to decide who with blood in the urine needs a camera test","aka":[],"tldr":"Most people referred for blood in the urine do not have bladder cancer, yet all get cystoscopy. A urine DNA or methylation test could safely spare most of them.","summary":"Most people referred with blood in the urine do not have bladder cancer, yet all undergo cystoscopy, so this idea uses a urinary DNA methylation or mutation test to decide who needs the camera test. Biomarker-negative patients would be randomised to deferred versus immediate cystoscopy, with missed muscle-invasive cancer as the safety endpoint and cystoscopies avoided as the efficacy endpoint. Cystoscopy capacity is a rate-limiting step for urology worldwide and urinary assays report high negative predictive value, so safe triage could spare most patients. The test is a 3,000-patient RCT with a pre-agreed non-inferiority margin. At early-clinical maturity it addresses the bottlenecks The hardest cancers are found late and Overdiagnosis and false alarms.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The hardest cancers are found late): Crosby et al., Early detection of cancer (Science 2022)","url":"https://doi.org/10.1126/science.aay9040"}],"tags":[],"related":[],"cancers":["urothelial"],"sections":["early-detection","diagnostics"],"technologies":["liquid-biopsy","methylation-profiling"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["ppv"],"trials":[],"people":[],"bottlenecks":["b-early-detection","b-overdiagnosis"],"keyPapers":["paper-crosby-science"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Biomarker triage reduces cystoscopies by at least half with a missed high-grade cancer rate below 0.5%.","rationale":"Bladder cancer prevalence in haematuria referrals is 5-10%; cystoscopy capacity is a rate-limiting step for urology worldwide.","test":"Run a 3,000-patient RCT with a pre-agreed non-inferiority margin.","maturity":"early-clinical","actor":"clinic","cost":"medium","horizonYears":3},{"id":"idea-prev-hpylori-childhood-vaccine","kind":"idea","name":"A vaccine against H. pylori for children in high-risk regions","aka":[],"tldr":"A childhood vaccine against the stomach bacterium behind most stomach cancer would prevent infection for life. One trial in China showed protection; the idea has stalled.","summary":"An oral recombinant urease B vaccine showed about 72% efficacy against infection in a Chinese phase 3 in children (published 2015) but was not developed further. Propose a renewed programme of mucosal or mRNA vaccines against urease, CagA and VacA with infection-prevention and gastric precancer endpoints in high-incidence cohorts.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Prevention we already have is not deployed): Islami et al., Proportion of cancer attributable to modifiable risk factors (CA 2018)","url":"https://doi.org/10.3322/caac.21440"}],"tags":[],"related":[],"cancers":["gastric"],"sections":["prevention"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption"],"keyPapers":["paper-islami-ca-cancer-j-clin"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A vaccine reducing childhood H. pylori acquisition by at least 60% reduces atrophic gastritis at age 30 by at least 40% and, long term, gastric cancer incidence.","rationale":"The bacterium is a defined carcinogen; preventing chronic infection prevents the disease pathway, as HBV vaccination did for liver cancer.","test":"Phase 2 immunogenicity and infection-prevention trial in 5,000 children with three-year follow-up.","maturity":"early-clinical","actor":"philanthropy","cost":"large","horizonYears":12},{"id":"idea-moon-verified-information-layer","kind":"idea","name":"A verified information layer that labels and links cancer content across platforms","aka":[],"tldr":"Wherever cancer information appears online, a visible marker shows whether it matches what trusted sources say, with a one-click link to the plain-language evidence.","summary":"Platforms label some health content but coverage is thin and inconsistent. The proposal is an open, machine-readable registry of vetted cancer claims and sources (national cancer institute, cancer charities, guideline bodies) that platforms, browsers and AI assistants can query, delivered as a browser extension and platform API, with labels that link to plain-language summaries and disclose the sourcing. Independent governance keeps it credible.","asOf":"2026-09-08","links":[{"label":"NCI PDQ cancer information summaries","url":"https://www.cancer.gov/publications/pdq"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-misinformation","b-knowledge-diffusion"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Content carrying the verified label is trusted and shared more, and exposure to labelled contradictions reduces belief in false cancer claims in randomised exposure studies.","rationale":"Credibility signals work when they are consistent, independent and easy to check; the missing piece is a shared open registry rather than each platform improvising.","test":"Build the registry for 500 common claims; randomised online experiment measuring belief and sharing with and without the layer; then a browser extension pilot with patient organisations.","maturity":"speculative","actor":"engineering","cost":"small","horizonYears":2},{"id":"idea-fund-surgical-video-registry","kind":"idea","name":"A video-based surgical quality registry linking assessed skill to cancer outcomes","aka":[],"tldr":"Surgeons' skill affects whether cancer comes back, but nobody measures it. Recording operations and rating them, increasingly with AI, then linking ratings to outcomes, would make surgical quality visible and improvable.","summary":"A registry in which cancer operations are routinely video-recorded, rated for technical skill by blinded peers and validated computer-vision tools, and linked to pathological (margins, lymph node yield) and oncological outcomes. Michigan's bariatric surgery collaborative showed that peer-rated skill predicts complications; oncology studies have linked skill ratings to margin status and survival. The registry supports credentialling for trials, targeted coaching, learning-curve monitoring for new techniques, and eventually AI feedback during surgery. Consent, data protection and non-punitive governance are the hard parts and must be designed with surgeons.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Surgery and radiotherapy cure most, get least): Sullivan et al., Global cancer surgery (Lancet Oncology Commission 2015)","url":"https://doi.org/10.1016/S1470-2045(15)00223-5"}],"tags":[],"related":["idea-fund-surgical-trials-network","idea-fund-device-technique-registry","idea-fund-surgical-outcomes-public-reporting"],"cancers":["colorectal","prostate","gastric"],"sections":[],"technologies":["robotic-surgery","digital-pathology-ai"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-surgery-radiation-innovation","b-real-world-evidence"],"keyPapers":["paper-sullivan-lancet-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Surgeons who receive video-based skill feedback improve rated skill and reduce positive margin rates measurably within two years, and registry skill scores predict recurrence independently of volume and stage.","rationale":"Skill-outcome associations have been shown in bariatric, colorectal and prostate surgery; video review with feedback improves technical scores in randomised studies of trainees. Making this systematic is an infrastructure and governance problem, not a scientific one.","test":"Enrol twenty centres, record and rate a defined operation for two years, and test skill-outcome associations and the effect of feedback in a stepped-wedge design.","maturity":"early-clinical","actor":"data","cost":"medium","horizonYears":3},{"id":"idea-bio1-virtual-cell-perturbation","kind":"idea","name":"A virtual cancer cell that predicts what a drug will do before you test it","aka":[],"tldr":"Train a model on millions of experiments where genes and drugs were altered, so it can predict the effect of a new combination without running the experiment.","summary":"Perturbation foundation models trained on Perturb-seq, CRISPR screens and compound-response atlases aim to predict transcriptional and viability responses to unseen perturbations and combinations. The critical missing element is prospective, blinded validation against held-out wet-lab experiments and, eventually, clinical outcomes. Without that, these models risk repeating the overfitting seen in earlier drug-response prediction efforts.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Lab models that fail to predict what happens in patients): Wong, Siah & Lo, Estimation of clinical trial success rates (Biostatistics 2019)","url":"https://doi.org/10.1093/biostatistics/kxx069"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["ai-drug-design","crispr-screens","rna-seq"],"targets":[],"drugs":[],"companies":["recursion","insilico-medicine"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-preclinical-models","b-ai-validation","b-combination-space"],"keyPapers":["paper-wong-biostatistics"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A perturbation model prospectively predicts the direction and rank order of combination effects in held-out cell contexts substantially better than a strong statistical baseline, and its errors are systematic and characterisable.","rationale":"Combination space is far too large to screen exhaustively, so some form of prediction is unavoidable; the question is whether current models generalise beyond their training distribution, which only blinded prospective tests can answer.","test":"A blinded challenge in which teams predict outcomes of 500 unseen perturbation experiments that are then run in a reference laboratory, with results and baselines published in full.","maturity":"speculative","actor":"data","cost":"medium","horizonYears":4},{"id":"idea-prev-blood-precursor-watch-registry","kind":"idea","name":"A watch-and-wait registry for blood precursor conditions found by chance","aka":[],"tldr":"Blood tests increasingly find precursor conditions like MGUS and smouldering myeloma, but most never progress. A registry with clear rules would stop early treatment outside trials.","summary":"Smouldering myeloma treatment trials prompt calls for early therapy, yet most patients would never progress; iStopMM (Iceland) shows population MGUS screening is feasible. Propose a national precursor registry (MGUS, smouldering myeloma, monoclonal B-cell lymphocytosis, CHIP) with risk stratification, no treatment outside trials, and patient-reported outcomes.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Overdiagnosis and false alarms): Welch & Black, Overdiagnosis in cancer (JNCI 2010)","url":"https://doi.org/10.1093/jnci/djq099"}],"tags":[],"related":[],"cancers":["multiple-myeloma","cll"],"sections":["early-detection"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-overdiagnosis"],"keyPapers":["paper-welch-j-natl-cancer-inst"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A stratified registry allows at least 80% of precursor patients to remain untreated over ten years while progression is detected before end-organ damage in at least 90% of those who progress.","rationale":"The harm to avoid is treatment creep as detection expands.","test":"Registry with pre-specified progression monitoring; compare outcomes with treated cohorts.","maturity":"early-clinical","actor":"clinic","cost":"medium","horizonYears":6},{"id":"idea-moon-population-interception","kind":"idea","name":"A whole-population cancer interception programme: risk-stratify every adult, detect and intercept early","aka":[],"tldr":"Instead of separate screening programmes for a few cancers, assess every adult's overall cancer risk and offer blood tests, imaging and preventive treatment tuned to that risk, all inside one system that learns.","summary":"Screening today covers a handful of cancers with organ-specific programmes and reaches a fraction of eligible people. Multi-cancer early detection blood tests (NHS-Galleri, PATHFINDER 2) and polygenic, exposure and imaging-based risk models make a unified approach conceivable: every adult over 40 receives a risk profile, a personalised detection schedule, and where indicated interception (chemoprevention, vaccines, risk-reducing procedures), with all results feeding a national learning system that recalibrates the models. Overdiagnosis is controlled through molecular indolence classifiers and surveillance-first protocols.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The hardest cancers are found late): Crosby et al., Early detection of cancer (Science 2022)","url":"https://doi.org/10.1126/science.aay9040"}],"tags":[],"related":["idea-mced-plus-fapi"],"cancers":[],"sections":[],"technologies":["mced","liquid-biopsy","chemoprevention","whole-body-mri"],"targets":[],"drugs":["galleri"],"companies":[],"institutions":[],"pathways":[],"terms":["stage-shift","ppv"],"trials":["nhs-galleri","pathfinder-2"],"people":[],"bottlenecks":["b-early-detection","b-prevention-adoption","b-overdiagnosis"],"keyPapers":["paper-crosby-science"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A unified risk-stratified programme reduces late-stage (III/IV) cancer incidence across all cancers by at least 20% within a decade at acceptable cost per life-year, without increasing overtreatment of indolent disease.","rationale":"Stage at diagnosis is the strongest determinant of survival, most cancers have no screening, and organ-by-organ programmes cannot scale to thirty diseases. Risk models and blood-based detection convert the problem into a systems problem.","test":"A regional cluster-randomised implementation of the programme versus standard screening with stage-shift, cancer-specific mortality and overdiagnosis metrics at five years, building on the NHS-Galleri infrastructure.","maturity":"speculative","actor":"policy","cost":"large","horizonYears":10},{"id":"idea-data-accredited-tre-network","kind":"idea","name":"Accredited trusted research environments with curated cancer tables","aka":[],"tldr":"Secure online workrooms where approved researchers can analyse cancer records without downloading them, with the data already cleaned and organised for cancer questions.","summary":"Trusted research environments (TREs) under the Five Safes model are now the default in the UK (NHS Secure Data Environments, OpenSAFELY) and emerging elsewhere. What is missing for oncology is curation: standardised, documented cancer tables (diagnosis, stage, treatment lines, response, death) refreshed on a schedule, so every study does not rebuild them. The proposal funds a small curation team per TRE and an accreditation standard for cancer-ready TREs.","asOf":"2026-09-08","links":[{"label":"OpenSAFELY","url":"https://www.opensafely.org/"}],"tags":[],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["real-world-evidence"],"trials":[],"people":[],"bottlenecks":["b-data-silos","b-reproducibility"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Curated cancer tables in a TRE reduce analyst time per study by more than half and increase reproducibility across studies using the same derivation code.","rationale":"OpenSAFELY showed that shared, versioned derivation code and a fixed environment produce fast, reproducible analyses at national scale during COVID-19; oncology has no equivalent curated layer.","test":"Give two analyst teams the same question, one in a TRE with curated tables and one with raw tables; measure time to answer and agreement of results. Repeat for five questions.","maturity":"being-tested-at-scale","actor":"data","cost":"medium","horizonYears":2},{"id":"idea-prev-ptmc-active-surveillance-default","kind":"idea","name":"Active surveillance as the default for tiny papillary thyroid cancers","aka":[],"tldr":"Papillary thyroid cancers under 1 cm almost never cause harm. Japanese hospitals have watched thousands safely. Make watching, not surgery, the default everywhere, with a registry.","summary":"Kuma Hospital and Cancer Institute Hospital (Tokyo) cohorts show under 1% distant progression and no disease deaths over decades of surveillance for low-risk papillary microcarcinoma. Propose making surveillance the default option in guidelines, with an international registry, a standardised ultrasound protocol, and reimbursement parity with surgery.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Overdiagnosis and false alarms): Welch & Black, Overdiagnosis in cancer (JNCI 2010)","url":"https://doi.org/10.1093/jnci/djq099"}],"tags":[],"related":[],"cancers":["thyroid"],"sections":["early-detection"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["jfcr"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-overdiagnosis"],"keyPapers":["paper-welch-j-natl-cancer-inst"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Default surveillance reduces surgery for papillary microcarcinoma by at least 60% with disease-specific mortality unchanged and lower rates of hypoparathyroidism and nerve injury.","rationale":"Long-term Japanese outcomes have been replicated in US and Korean pilots.","test":"Registry-based comparison plus a randomised decision-aid trial on uptake of surveillance.","maturity":"being-tested-at-scale","actor":"clinic","cost":"small","horizonYears":3},{"id":"idea-tr2-fdaaa-enforcement","kind":"idea","name":"Actually fine sponsors who do not post trial results","aka":[],"tldr":"US law already requires trial results to be posted within a year and allows fines of over ten thousand dollars a day. Almost no fines have ever been issued. Start issuing them.","summary":"FDAAA 801 requires results posting on ClinicalTrials.gov within twelve months of primary completion for applicable trials; compliance has hovered around 40 to 70% depending on sponsor type. Enforcement has been minimal. A published enforcement policy with automatic notices, escalating penalties and public listing of non-compliant sponsors, plus an equivalent under the EU Clinical Trials Regulation, would raise compliance.","asOf":"2026-09-08","links":[{"label":"FDAAA TrialsTracker","url":"https://fdaaa.trialstracker.net/"}],"tags":[],"related":["clinicaltrials-gov","eudract-ctis"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-negative-results"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Systematic enforcement raises on-time results posting for oncology trials above 90% within two years, as measured by the TrialsTracker methodology.","rationale":"When the EU Clinical Trials Register began publicly listing non-compliance and universities faced reputational pressure, UK university compliance rose from under 50% to over 90% in about two years.","test":"Implement and publish the enforcement policy; track monthly compliance rates against the pre-policy baseline.","maturity":"early-clinical","actor":"regulator","cost":"small","horizonYears":1},{"id":"idea-acc-acute-oncology-assessment-units","kind":"idea","name":"Acute oncology assessment units so sick cancer patients bypass the emergency department","aka":[],"tldr":"A cancer patient with a fever or severe sickness during treatment should be seen quickly by a team that knows chemotherapy, not wait hours in a general emergency room.","summary":"Cancer patients present to emergency departments frequently during treatment and are often admitted when same-day specialist assessment would have avoided it. Acute oncology services and dedicated assessment units (established across the UK and in some US centres) provide a direct line, rapid triage, and protocolised management for neutropenic fever, dehydration, and immune-related toxicity. The proposal is to make such a unit a required component of every treating centre.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Fragmented care and guideline gaps): Hanna et al., Mortality due to cancer treatment delay: systematic review and meta-analysis (BMJ 2020)","url":"https://doi.org/10.1136/bmj.m4087"}],"tags":[],"related":[],"cancers":[],"sections":["supportive-care"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-care-fragmentation","b-toxicity-qol"],"keyPapers":["paper-hanna-bmj"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Centres with an acute oncology assessment unit will reduce emergency-department attendances by treated patients by at least 30% and reduce admissions for low-risk febrile neutropenia by half.","rationale":"Direct access to specialist assessment avoids the delays and defaults of general emergency medicine, where admission is the safe reflex for unfamiliar toxicities.","test":"A before-and-after evaluation with emergency attendances, admissions, length of stay, and time-to-antibiotic for febrile neutropenia as endpoints.","maturity":"being-tested-at-scale","actor":"clinic","cost":"medium","horizonYears":2},{"id":"idea-post-neoadjuvant-adc","kind":"idea","name":"ADC for residual disease after KEYNOTE-522","aka":[],"tldr":"Patients whose TNBC survives chemo-immunotherapy before surgery have a high relapse risk. Give them an ADC after surgery.","summary":"Patients whose TNBC survives neoadjuvant chemo-immunotherapy carry a high relapse risk, and this idea gives them a TROP2 ADC, with or without pembrolizumab, after surgery. It applies the KATHERINE model, T-DM1 for HER2-positive residual disease, to TNBC with residual cancer burden after KEYNOTE-522 therapy. Residual disease is chemoresistant but not necessarily ADC-resistant, because the payload is delivered at concentrations chemotherapy cannot reach. The concept is being tested at scale in ASCENT-05 with sacituzumab govitecan plus pembrolizumab and in TROPION-Breast03 with datopotamab deruxtecan, and ctDNA-defined high-risk subgroups should be pre-specified. It forms part of the TNBC roadmap.","asOf":"2026-09-04","links":[{"label":"ClinicalTrials.gov NCT03036488: KEYNOTE-522","url":"https://clinicaltrials.gov/study/NCT03036488"}],"tags":[],"related":[],"cancers":["tnbc"],"sections":[],"technologies":["adc"],"targets":[],"drugs":["sacituzumab-govitecan","datopotamab-deruxtecan","pembrolizumab"],"companies":[],"institutions":[],"pathways":[],"terms":["rcb","pcr"],"trials":["keynote-522"],"people":[],"bottlenecks":[],"keyPapers":["paper-keynote-522-n-engl-j-med-2020","paper-keynote-355-lancet-2020","paper-ascent-nejm-2021"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Adjuvant TROP2 ADC ± pembrolizumab improves iDFS in TNBC with residual disease (RCB I-III) after neoadjuvant KEYNOTE-522 therapy compared with pembrolizumab ± capecitabine.","rationale":"Residual disease is chemoresistant but not necessarily ADC-resistant; ADC payload is delivered at concentrations chemotherapy cannot reach.","test":"ASCENT-05 and TROPION-Breast03 readouts expected 2026-27; ctDNA-defined high-risk subgroups should be pre-specified.","maturity":"being-tested-at-scale"},{"id":"idea-reg-factorial-addon-arms-cooperative-trials","kind":"idea","name":"Add a cheap-drug factorial arm to every cooperative-group adjuvant cancer trial","aka":[],"tldr":"Large adjuvant trials already follow thousands of patients for years. Adding a second randomisation to a cheap old drug would answer repurposing questions almost for free.","summary":"Factorial designs randomise the same patients to two independent questions, sharing recruitment, follow-up and infrastructure. Add-Aspirin ran as a standalone trial; embedding similar questions as second factors in cooperative-group adjuvant trials (breast, colorectal, lung, prostate) would multiply the number of repurposing questions answered at a small marginal cost. The proposal is a policy by public trial funders (NCI cooperative groups, CRUK, EORTC) that every new large adjuvant trial include, where feasible, a factorial randomisation to a prioritised off-patent candidate, with a central committee selecting candidates and monitoring interactions.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (No incentive to repurpose cheap drugs): Pantziarka et al., The Repurposing Drugs in Oncology (ReDO) Project (ecancer 2014)","url":"https://doi.org/10.3332/ecancer.2014.442"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["nci","cruk"],"pathways":[],"terms":["neoadjuvant-adjuvant"],"trials":[],"people":[],"bottlenecks":["b-generic-repurposing","b-trial-design"],"keyPapers":["paper-pantziarka-ecancermedicalscience"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Factorial add-ons answer at least one repurposing question per two adjuvant trials at less than 10% additional cost per trial, without compromising the primary question's power or recruitment.","rationale":"The main cost of an adjuvant trial is following patients for years; a second factor uses that investment twice. Interaction between factors is a manageable statistical risk when candidates are chosen for independent mechanisms.","test":"Embed factorial arms in the next three cooperative-group adjuvant trials and report recruitment, cost increment and analysability against the groups' previous trials.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":6},{"id":"idea-bio1-molecular-progression-add-on","kind":"idea","name":"Add a drug when the blood test turns, without stopping the one that works","aka":[],"tldr":"When a resistance mutation first appears in the blood, the current drug is often still controlling most of the tumour. Adding a second drug rather than swapping may keep both under control.","summary":"Most ctDNA-guided strategies switch therapy at molecular progression. Because the resistant clone is usually a minority at that point, switching abandons control of the sensitive majority. An additive strategy keeps the backbone and adds a mechanism-matched agent when a specific resistance alteration crosses a threshold in plasma, with the aim of suppressing both populations.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Acquired resistance to every therapy): Soria et al., Osimertinib in untreated EGFR-mutated NSCLC (FLAURA, NEJM 2018)","url":"https://doi.org/10.1056/NEJMoa1713137"}],"tags":[],"related":["idea-ctdna-switch-generalised"],"cancers":["nsclc"],"sections":[],"technologies":["liquid-biopsy"],"targets":["met","egfr"],"drugs":["osimertinib","amivantamab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-resistance","b-trial-design"],"keyPapers":["paper-flaura-nejm-2018","paper-osimertinib-nsclc-n-engl-j-med-2017","paper-osimertinib-nsclc-n-engl-j-med-2020"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Mechanism-matched addition at molecular progression yields longer time to radiographic progression than either continuing alone or switching, in patients with a single dominant emergent mechanism.","rationale":"Combination at the point of minimal resistant burden is when the added agent has the best chance of eradicating the emergent clone, and the backbone still suppresses the dominant population.","test":"Three-arm randomised phase 2 at molecular progression on osimertinib with detectable MET amplification: continue, switch, or add a MET inhibitor; primary endpoint time to radiographic progression.","maturity":"speculative","actor":"clinic","cost":"medium","horizonYears":5},{"id":"idea-bio1-upfront-bypass-combination","kind":"idea","name":"Add the second drug on day one when the escape route is predictable","aka":[],"tldr":"If most tumours escape a drug by the same back-up route, blocking that route from the start may prevent resistance rather than chase it.","summary":"For several targeted agents the dominant bypass is known in advance: MET amplification after EGFR inhibition, RTK and MAPK reactivation after KRAS G12C inhibition, and MEK reactivation after BRAF inhibition (which is why BRAF and MEK inhibitors are combined). Extending upfront combination logic requires tolerability, so intermittent scheduling or lower-dose partner agents should be part of the design.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Acquired resistance to every therapy): Soria et al., Osimertinib in untreated EGFR-mutated NSCLC (FLAURA, NEJM 2018)","url":"https://doi.org/10.1056/NEJMoa1713137"}],"tags":[],"related":[],"cancers":["nsclc"],"sections":[],"technologies":[],"targets":["egfr","met","kras","braf"],"drugs":["osimertinib","sotorasib","amivantamab"],"companies":[],"institutions":[],"pathways":["ras-mapk"],"terms":[],"trials":["adaura","flaura","flaura2","mariposa","rtog-0617"],"people":[],"bottlenecks":["b-resistance","b-combination-space","b-dose-optimisation"],"keyPapers":["paper-flaura-nejm-2018","paper-egfr-nsclc-lancet-oncol-2012","paper-egfr-nsclc-n-engl-j-med-2010"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Upfront combination against the dominant predicted bypass extends progression-free survival by more than 50 percent relative to sequential addition at progression, at acceptable added toxicity.","rationale":"BRAF plus MEK inhibition proved the principle, converting a short-lived response into a durable one; the same logic has not been systematically applied to other classes because tolerability was assumed prohibitive without testing schedules.","test":"Randomised phase 2 of upfront versus at-progression addition of a bypass-directed agent in a setting with a well-documented dominant mechanism, with dose-optimised intermittent schedules.","maturity":"early-clinical","actor":"industry","cost":"medium","horizonYears":5},{"id":"idea-reg-tumour-agnostic-reliance","kind":"idea","name":"Adopt tumour-agnostic cancer drug labels across regions by reliance, not re-review","aka":[],"tldr":"Some drugs work on a genetic change whatever the cancer. When one regulator approves such a label, others should adopt it rather than demanding trials per cancer type.","summary":"Tumour-agnostic approvals (NTRK fusions, MSI-high, BRAF V600E, RET) rest on basket trials that some regulators have accepted and others have restricted to specific tumour types, producing labels that differ by region for the same evidence. Patients with rare tumours in restrictive regions are excluded. The proposal is a standing agreement that tumour-agnostic indications granted by one stringent regulator on basket-trial evidence are adopted by partners within 90 days, with a shared post-marketing registry to fill evidence gaps in rare histologies.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Regulatory divergence between regions): FDA Oncology Center of Excellence, Project Orbis","url":"https://www.fda.gov/about-fda/oncology-center-excellence/project-orbis"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":["ntrk","braf","ret"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["tumour-agnostic","basket-umbrella-platform"],"trials":[],"people":[],"bottlenecks":["b-regulatory-fragmentation","b-rare-cancers"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Regional divergence in tumour-agnostic labels falls to zero for new approvals, and patients with rare cancers in adopting regions gain access a median of two years earlier than under current sequential review.","rationale":"Basket-trial evidence is inherently sparse per histology; asking for more per-tumour data from each region is a demand that cannot be met and simply denies access. A shared registry produces better evidence than any region could alone.","test":"Document current divergence for the existing tumour-agnostic indications across ten regulators; pilot reciprocal adoption for the next two tumour-agnostic approvals with a shared registry.","maturity":"speculative","actor":"regulator","cost":"small","horizonYears":3},{"id":"idea-fund-amc-paediatric-rare","kind":"idea","name":"Advance market commitments for paediatric and rare cancer drugs","aka":[],"tldr":"Payers would promise in advance to buy a set number of doses at a set price for any drug that meets a defined bar in a rare or childhood cancer, so companies know the market exists before they invest.","summary":"Modelled on Gavi's pneumococcal advance market commitment, a consortium of national payers and foundations pledges a guaranteed purchase (volume times price, for example $300 million over ten years) for the first therapy meeting a target product profile in a specified rare or paediatric indication: diffuse midline glioma, relapsed neuroblastoma, Ewing sarcoma, rare fusion-driven cancers. In exchange, the developer accepts a long-run affordable price and supply commitments. The commitment is only paid on delivery of a product that meets pre-registered efficacy criteria, so payers bear no risk of failure.","asOf":"2026-09-08","links":[{"label":"Gavi pneumococcal Advance Market Commitment","url":"https://www.gavi.org/investing-gavi/innovative-financing/pneumococcal-amc"}],"tags":[],"related":["idea-fund-paediatric-deferral-escrow","idea-fund-nonprofit-pharma"],"cancers":["neuroblastoma","sarcoma","glioblastoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["childrens-oncology-group"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-incentive-misalignment","b-rare-cancers"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"An AMC of a few hundred million dollars for a named paediatric indication brings at least two registration-intent programmes into that indication within five years where there were none, and shortens time from adult approval to paediatric labelling for eligible mechanisms.","rationale":"The pneumococcal AMC accelerated vaccine availability in poor countries by years and drew in new manufacturers. Paediatric oncology drug development is delayed by uncertain and small markets; the RACE Act mandates studies but does not make them profitable. A guaranteed market is the missing pull.","test":"Design one AMC with a target product profile and escrowed funds for a single indication, publish it, and count programme entries and phase 1/2 starts in that indication over five years against comparable indications.","maturity":"speculative","actor":"payer","cost":"large","horizonYears":6},{"id":"idea-acc-advanced-practice-radiation-therapists","kind":"idea","name":"Advanced-practice radiation therapists doing contouring and on-treatment reviews","aka":[],"tldr":"Radiation therapists, the staff who deliver daily treatment, can be trained to outline normal organs on scans and to review patients during treatment, work that oncologists now do.","summary":"The UK, Canada, and Australia have advanced-practice radiation therapist roles covering organ-at-risk contouring, on-treatment review, palliative planning, and image-guidance decisions, with evidence of equivalence to physician performance and reduced waiting times. Most countries have no such role. Recognising and funding advanced practice would enlarge the effective workforce without new professions.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Not enough oncologists, nurses, pathologists, physicists): Yang et al., Projected supply of and demand for oncologists and radiation oncologists through 2025 (JOP 2014)","url":"https://doi.org/10.1200/JOP.2013.001319"}],"tags":[],"related":[],"cancers":[],"sections":["radiation"],"technologies":["imrt-igrt"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-workforce","b-surgery-radiation-innovation"],"keyPapers":["paper-yang-j-oncol-pract"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Departments with advanced-practice therapists will cut referral-to-treatment time by at least 20% and free at least 15% of oncologist clinical time, with contouring concordance to oncologist reference at or above inter-oncologist variability.","rationale":"Contouring of normal structures and routine on-treatment review are protocol-driven tasks well suited to a trained non-physician workforce, as demonstrated in existing programmes.","test":"A multi-centre implementation study with blinded contour-concordance scoring, waiting-time and physician-time measurements, and patient experience surveys.","maturity":"being-tested-at-scale","actor":"regulator","cost":"small","horizonYears":2},{"id":"idea-tr1-post-approval-pragmatic-trial-in-excluded","kind":"idea","name":"After approval, a pragmatic trial in the patients the pivotal trial excluded","aka":[],"tldr":"Drugs are approved on trials of fit, younger patients and then given to everyone. A required follow-on trial in older, sicker and more diverse patients would show whether the benefit holds in real life.","summary":"As a condition of approval, sponsors fund a pragmatic randomised trial with broad eligibility run in community settings, using routinely collected endpoints (OS, hospitalisation, treatment discontinuation) and minimal extra visits, modelled on the FDA's Project Pragmatica and the Pragmatica-Lung trial. Results feed label updates on dosing and benefit in the broader population.","asOf":"2026-09-08","links":[{"label":"FDA Oncology Center of Excellence: Project Pragmatica","url":"https://www.fda.gov/about-fda/oncology-center-excellence/project-pragmatica"},{"label":"Pragmatica-Lung (S2302) on ClinicalTrials.gov","url":"https://clinicaltrials.gov/study/NCT05633602"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["nci"],"pathways":[],"terms":["real-world-evidence"],"trials":[],"people":[],"bottlenecks":["b-trial-design","b-real-world-evidence","b-aging-comorbidity"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Pragmatic confirmatory trials will show a smaller but still positive effect in most cases and will identify at least some approved regimens whose benefit does not extend to the real-world population, leading to label changes.","rationale":"Real-world outcomes are often worse than trial outcomes, and it is unknown how much is due to population differences versus care. Only randomisation in the broad population resolves this.","test":"Track Pragmatica-Lung and the next five such trials for enrolment speed, cost per patient and concordance with the pivotal effect size.","maturity":"early-clinical","actor":"regulator","cost":"large","horizonYears":4},{"id":"idea-prev-low-risk-dcis-surveillance-pathway","kind":"idea","name":"After the COMET trial: surveillance pathways and a new name for low-risk DCIS","aka":[],"tldr":"Low-risk DCIS is a breast change that may never become cancer. Trials now show watching it is safe in the short term. The next step is a proper pathway and a name that does not say cancer.","summary":"COMET (US) reported two-year outcomes supporting active monitoring of low-risk DCIS; LORIS and LORD add European data. Propose an implementation programme: eligibility criteria, imaging protocol, an endocrine therapy option, a registry with safety stopping rules, and a terminology change tested for its effect on choice.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Overdiagnosis and false alarms): Welch & Black, Overdiagnosis in cancer (JNCI 2010)","url":"https://doi.org/10.1093/jnci/djq099"}],"tags":[],"related":[],"cancers":["breast-hr-positive"],"sections":["early-detection"],"technologies":["mammography"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-overdiagnosis"],"keyPapers":["paper-welch-j-natl-cancer-inst"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Implementation halves surgery for low-risk DCIS with ipsilateral invasive cancer at five years no more than 3 percentage points above the surgery arm rate.","rationale":"Terminology drives treatment choice in experiments; pathways make surveillance the safe rather than the brave option.","test":"Registry with pre-specified safety rules and an embedded randomised trial of terminology on decision.","maturity":"being-tested-at-scale","actor":"clinic","cost":"medium","horizonYears":5},{"id":"idea-tr1-aggregated-n-of-1-supportive-care","kind":"idea","name":"Aggregated single-patient crossover trials for symptom and supportive treatments","aka":[],"tldr":"For symptoms such as nausea, fatigue or neuropathy, each patient can alternate the drug and a placebo over several periods and learn what works for them. Pooling these single-patient crossover trials with Bayesian models also gives a population answer, in areas where conventional trials are rare.","summary":"N-of-1 trials (multiple randomised crossover periods within one patient) with ePRO outcomes are aggregated across patients using Bayesian hierarchical models to estimate both population and individual effects. Suitable for chronic, stable symptoms and reversible treatments (antiemetics, neuropathic pain agents, appetite stimulants, sleep aids) where conventional RCTs are rare because there is little commercial incentive.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Trial design, endpoints and cost): Davis et al., Availability of evidence of benefits on survival and quality of life of cancer drugs approved by EMA 2009-13 (BMJ 2017)","url":"https://doi.org/10.1136/bmj.j4530"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["exercise-oncology"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-design","b-cachexia-supportive"],"keyPapers":["paper-davis-bmj"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Aggregated N-of-1 designs will answer supportive-care questions with a fifth of the patients required by parallel-group trials and will give each participant a personal answer they act on.","rationale":"Supportive care is under-researched relative to its impact on QoL. N-of-1 designs are statistically efficient for stable conditions and are inherently patient-centred.","test":"Run a platform of N-of-1 trials for three common symptoms in a survivorship clinic with a smartphone ePRO app and compare precision per patient with the literature.","maturity":"speculative","actor":"research","cost":"small","horizonYears":2},{"id":"idea-bio2-bayesian-borrowing-acceptance","kind":"idea","name":"Agree in advance how to borrow evidence between similar rare cancers","aka":[],"tldr":"Statistical methods can combine information across similar rare cancers to reach an answer with fewer patients. Regulators need to say in advance when that is acceptable.","summary":"Hierarchical Bayesian models with borrowing across histologies or across related rare diseases can substantially reduce required sample size, and are used in basket trial analyses. Sponsors avoid them because acceptance is uncertain at review. A published position on acceptable borrowing structures, prior specification and pre-registration requirements would let sponsors design smaller trials with confidence.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Rare and paediatric cancers without markets): Gatta et al., Rare cancers are not so rare: the rare cancer burden in Europe (EJC 2011)","url":"https://doi.org/10.1016/j.ejca.2011.08.008"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["esmo","asco"],"pathways":[],"terms":["basket-umbrella-platform","hazard-ratio"],"trials":[],"people":[],"bottlenecks":["b-rare-cancers","b-trial-design","b-regulatory-fragmentation"],"keyPapers":["paper-gatta-eur-j-cancer"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Regulatory clarity on borrowing methods reduces the median sample size of rare cancer registrational trials by a third without increasing the rate of subsequent effect reversals in confirmatory data.","rationale":"Similar clarity on adaptive designs and on external control arms rapidly changed practice once guidance existed. The statistical machinery is mature; the missing element is a pre-agreed acceptability boundary.","test":"Simulation study across historical rare cancer datasets to quantify type I error and bias under candidate borrowing structures, submitted jointly by academic statisticians and regulators as the basis for guidance.","maturity":"speculative","actor":"regulator","cost":"small","horizonYears":4},{"id":"idea-rejuv-core-outcome-set-for-late-effects","kind":"idea","name":"Agree what to measure, so the next systematic review can pool rather than narrate","aka":[],"tldr":"A reported prevalence of 0 to 84 per cent for the same late effect is a measurement failure. Core outcome sets are cheap, need no new biology, and would unlock the studies the field has already paid for.","summary":"This is the least glamorous and probably the highest-return item on this agenda. Across this front, studies exist and cannot be combined: kidney impairment after childhood cancer is reported between 0 and 84 per cent with no agreed outcome measure; nail changes after chemotherapy between 0 and 44 per cent; time to diagnosis in adolescents and young adults could not be meta-analysed at all because the distributions were incomparable; quality of life after a stoma or limb loss was measured inconsistently with scores varying substantially; fear of recurrence, the most reported unmet need in survivorship, still lacks consensus definitions and well-validated measures by its own field's assessment.\n\nA core outcome set specifies a minimum set of outcomes and the instrument for each, agreed by a structured consensus process including patients. It does not stop anyone measuring more. It costs a fraction of a single trial, and it changes what a decade of subsequent studies can be used for. The methodology is established in other fields and has been applied in oncology for specific tumour types.\n\nThe lever is not persuasion but funding and publication. A funder that requires the relevant core outcome set in any survivorship application, and a journal that requires it to be reported, changes practice faster than consensus alone.","asOf":"2026-10-02","links":[{"label":"Hudson et al., Clinical ascertainment of health outcomes among adults treated for childhood cancer (JAMA 2013;309:2371)","url":"https://doi.org/10.1001/jama.2013.6296"}],"tags":["rejuvenation","survivorship","open-problem","outcomes","methods"],"related":["rejuv-paed-kidneys","rejuv-ayac-diagnostic-delay","rejuv-mind-fear-of-recurrence","cognitive-impairment-after-cancer-treatment","idea-moon-pro-ctcae-in-every-pivotal-trial","ighg","rejuvenation-roadmap"],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["rejuv-agenda-no-agreed-outcome-measures","rejuv-agenda-nothing-restores-cognition","b-toxicity-qol","b-reproducibility"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Agreed core outcome sets for the principal late effects, with named instruments, would make the existing and future literature poolable and remove the commonest reason this field cannot state a number.","rationale":"At least seven records written in this round state a named gap where a prevalence should be, each because the underlying studies used incompatible measures. The cost of fixing that is a consensus process per outcome; the cost of not fixing it is that every systematic review in this field narrates instead of pooling and every trial argues about its endpoint from first principles.","test":"Run structured consensus processes, with survivors in the panel, for the highest-volume late effects: cognition, fatigue, kidney function, sexual function, lymphoedema, fear of recurrence and bowel function after pelvic radiotherapy. Then have a major funder require the relevant set in survivorship applications, and measure uptake in published studies three and five years later.","maturity":"speculative","actor":"research","cost":"small","horizonYears":4},{"id":"idea-prev-ldct-ai-negative-triage","kind":"idea","name":"AI clears the normal lung screening scans so radiologists read only the suspicious ones","aka":[],"tldr":"Most screening CT scans are normal. Letting a validated AI clear them, and sending only flagged scans to a radiologist, would let screening scale without more radiologists.","summary":"Autonomous AI triage for chest X-ray is already CE-marked; for low-dose CT, tools reach high sensitivity for nodules of 6 mm and above. Propose a prospective non-inferiority trial where AI-negative scans are not read by radiologists (safety net: random 10% audit), with missed-cancer rate at two years as the primary endpoint.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The hardest cancers are found late): Crosby et al., Early detection of cancer (Science 2022)","url":"https://doi.org/10.1126/science.aay9040"}],"tags":[],"related":[],"cancers":["nsclc"],"sections":["early-detection","imaging"],"technologies":["ct","radiology-ai-screening"],"targets":[],"drugs":[],"companies":["aidoc","lunit"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-early-detection","b-workforce","b-ai-validation"],"keyPapers":["paper-crosby-science"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"AI negative-triage removes at least half of reads from radiologists with a missed-cancer rate non-inferior (margin 0.5 per 1,000) to double reading.","rationale":"Radiologist capacity is the binding constraint on lung screening rollout in most countries; workload reduction, not detection, is the value.","test":"Two-arm prospective trial across three to five screening centres, about 50,000 scans, with registry-linked interval cancers.","maturity":"early-clinical","actor":"clinic","cost":"medium","horizonYears":4},{"id":"idea-prev-lung-nodule-ai-discharge","kind":"idea","name":"AI malignancy scores to end repeat scans and biopsies for benign lung nodules","aka":[],"tldr":"Most lung nodules on CT are harmless but trigger years of follow-up scans. A validated AI score could discharge low-risk nodules immediately.","summary":"Most lung nodules on CT are harmless but trigger years of follow-up scans, so this idea discharges AI-low-risk nodules at baseline instead of following them. Nodule AI improves discrimination over the Brock model, and follow-up imaging is a major cost and source of anxiety in screening and incidental nodule management. An RCT would compare immediate discharge of low-risk nodules with standard follow-up, using missed cancer at three years as the safety endpoint and scans and biopsies avoided as efficacy. The test is a multicentre RCT of 5,000 nodules. At early-clinical maturity it addresses the bottlenecks Overdiagnosis and false alarms and AI that is built but not validated or deployed.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Overdiagnosis and false alarms): Welch & Black, Overdiagnosis in cancer (JNCI 2010)","url":"https://doi.org/10.1093/jnci/djq099"}],"tags":[],"related":[],"cancers":["nsclc"],"sections":["early-detection","imaging"],"technologies":["ct","radiology-ai-screening"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-overdiagnosis","b-ai-validation"],"keyPapers":["paper-welch-j-natl-cancer-inst"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"AI-based discharge removes at least 40% of follow-up CTs and 25% of benign biopsies with missed cancers under 0.5%.","rationale":"Follow-up imaging burden is a major cost and anxiety source in screening and incidental nodule management.","test":"Run a multicentre RCT of 5,000 nodules.","maturity":"early-clinical","actor":"clinic","cost":"medium","horizonYears":4},{"id":"idea-ai-her2-low-scoring","kind":"idea","name":"AI quantification of HER2-low and HER2-ultralow","aka":[],"tldr":"Pathologists disagree about faint HER2 staining, yet that decision unlocks Enhertu. Let a validated algorithm do the counting.","summary":"Pathologists disagree about faint HER2 staining, yet that call decides who receives trastuzumab deruxtecan, so this idea hands the counting to a validated algorithm. A continuous AI-derived HER2 membrane score is expected to predict T-DXd benefit better than pathologist-assigned IHC categories and to reclassify some IHC 0 tumours as eligible, because benefit depends on a continuous delivery threshold that binned human scoring discards. The test is a retrospective analysis of DESTINY-Breast04 and DESTINY-Breast06 slides with an AI scorer, then prospective companion-diagnostic validation. At early-clinical maturity it addresses the bottlenecks Biomarkers are not validated or standardised and AI that is built but not validated or deployed.","asOf":"2026-09-04","links":[{"label":"DESTINY-Breast04: trastuzumab deruxtecan works in HER2-low breast cancer, creating a new treatable group (New England Journal of Medicine 2022)","url":"https://doi.org/10.1056/NEJMoa2203690"}],"tags":[],"related":["her2-low-to-tdxd"],"cancers":["breast-hr-positive","tnbc"],"sections":[],"technologies":["digital-pathology-ai","histopathology-ihc"],"targets":[],"drugs":["trastuzumab-deruxtecan"],"companies":[],"institutions":[],"pathways":[],"terms":["her2-low","ihc"],"trials":["destiny-breast04","destiny-breast06","nct05950945"],"people":[],"bottlenecks":[],"keyPapers":["paper-trastuzumab-deruxtecan-breast-hr-positive-ann-oncol-2026","paper-trastuzumab-deruxtecan-tnbc-esmo-open-2021","paper-trastuzumab-deruxtecan-tnbc-expert-opin-biol-ther-2021"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A continuous AI-derived HER2 membrane score predicts T-DXd benefit better than pathologist-assigned IHC categories, and reclassifies a meaningful fraction of IHC 0 tumours as eligible.","rationale":"T-DXd benefit depends on a delivery threshold, which is continuous; discretised human scoring loses information.","test":"Run a retrospective analysis of DESTINY-Breast04/06 slides with an AI scorer, then prospective companion-diagnostic validation.","maturity":"early-clinical"},{"id":"idea-prev-pathology-ai-borderline-anchor","kind":"idea","name":"AI second reads to stop borderline lesions being upgraded to cancer","aka":[],"tldr":"Whether a lesion is called precancer or cancer varies between pathologists, and over time the bar has drifted lower. AI reference reads could hold the line.","summary":"Inter-observer disagreement is high for DCIS versus atypia, Gleason pattern 3 versus 4, and melanocytic lesions; diagnostic drift inflates incidence. Propose AI reference classifiers calibrated to historical outcome-linked cohorts, used as mandatory second reads for borderline categories, with discordance triggering expert review.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Overdiagnosis and false alarms): Welch & Black, Overdiagnosis in cancer (JNCI 2010)","url":"https://doi.org/10.1093/jnci/djq099"}],"tags":[],"related":[],"cancers":[],"sections":["diagnostics"],"technologies":["digital-pathology-ai","pathology-foundation-model"],"targets":[],"drugs":[],"companies":["paige","pathai"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-overdiagnosis","b-ai-validation"],"keyPapers":["paper-welch-j-natl-cancer-inst"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"AI second reads reduce upgrade rates of borderline lesions by at least 20% and reduce inter-laboratory variation without increasing subsequent invasive cancer.","rationale":"Digital pathology AI already matches expert Gleason grading; anchoring to outcome-linked training sets counters drift.","test":"Multi-laboratory study comparing diagnosis rates with and without AI second read, with five-year outcome linkage.","maturity":"early-clinical","actor":"clinic","cost":"medium","horizonYears":4},{"id":"idea-prev-pancreas-ai-prediagnostic-ct","kind":"idea","name":"AI that spots pancreatic cancer on scans taken a year before diagnosis","aka":[],"tldr":"Pancreatic cancer is often visible in hindsight on earlier scans. Software trained on those pre-diagnostic scans could flag subtle changes while surgery is still possible.","summary":"Retrospective studies (Mayo Clinic, Johns Hopkins FELIX project) show deep learning detects pancreatic cancer on pre-diagnostic CTs 3-36 months before clinical diagnosis with high AUC. Propose training on multi-institution pre-diagnostic scan cohorts and prospective deployment on abdominal CTs of patients over 50 with new-onset diabetes or weight loss.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The hardest cancers are found late): Crosby et al., Early detection of cancer (Science 2022)","url":"https://doi.org/10.1126/science.aay9040"}],"tags":[],"related":[],"cancers":["pancreatic"],"sections":["early-detection","imaging"],"technologies":["ct","radiology-ai-screening"],"targets":[],"drugs":[],"companies":[],"institutions":["johns-hopkins","mayo-clinic"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-early-detection"],"keyPapers":["paper-crosby-science"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Prospective deployment in high-risk CT populations detects resectable (stage I-II) pancreatic cancer in at least half of flagged true positives, versus roughly 15% resectable at usual diagnosis.","rationale":"Pancreatic cancer survival is stage-dependent and the pre-diagnostic window is documented; incidence in new-onset diabetes over 50 (about 1%) is high enough to justify targeted use.","test":"Prospective cohort of 20,000 abdominal CTs in the target population, with two-year registry follow-up for sensitivity and PPV.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":4},{"id":"idea-tr1-ai-central-imaging-reads","kind":"idea","name":"AI-assisted central imaging reads to cut endpoint cost and variability","aka":[],"tldr":"Measuring tumours on scans for trials is slow, expensive and inconsistent between readers. Software that measures lesions and flags changes, checked by a radiologist, could make trial endpoints cheaper and more reliable.","summary":"Validated AI segmentation and lesion-tracking tools perform RECIST 1.1 measurements with radiologist adjudication only on flagged discordances, replacing dual blinded independent central review. Performance is locked and validated against historical BICR-adjudicated trial datasets before use; regulators accept the tool under a qualification pathway.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Trial design, endpoints and cost): Davis et al., Availability of evidence of benefits on survival and quality of life of cancer drugs approved by EMA 2009-13 (BMJ 2017)","url":"https://doi.org/10.1136/bmj.j4530"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["ct","radiology-ai-screening"],"targets":[],"drugs":[],"companies":["aidoc","lunit"],"institutions":[],"pathways":[],"terms":["recist","pfs"],"trials":[],"people":[],"bottlenecks":["b-trial-design","b-ai-validation"],"keyPapers":["paper-davis-bmj"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"AI-assisted central reads will match BICR progression dates within one assessment interval in more than 95 percent of cases, at less than half the cost and with lower inter-reader variance, without changing trial conclusions on re-analysis.","rationale":"Central imaging review is one of the largest fixed costs in phase 3 oncology trials and reader disagreement drives discordance between local and central PFS. Segmentation models now perform at expert level on common lesion types.","test":"Re-read the imaging archives of three completed phase 3 trials with the AI-assisted workflow and compare PFS hazard ratios and progression dates with the original BICR.","maturity":"early-clinical","actor":"engineering","cost":"medium","horizonYears":3},{"id":"idea-bio1-ai-binders-disordered-regions","kind":"idea","name":"AI-designed proteins that grip the floppy parts of cancer drivers","aka":[],"tldr":"MYC, fusion oncoproteins and transcription factors have shapeless, flexible regions that drugs cannot grip. Deep-learning protein design tools such as RFdiffusion may be able to invent binders that clamp them, for use as degradation handles, intrabodies or targeting domains for CAR and bispecific therapies rather than as drugs themselves.","summary":"Deep-learning protein design (RFdiffusion, AlphaFold-based hallucination) has produced high-affinity binders to structured targets and, increasingly, to peptides and disordered segments. Intrinsically disordered regions of MYC, fusion oncoproteins and transcription factors are the classic undruggable surfaces. Designed binders could serve as degradation handles, intrabodies, or CAR and bispecific targeting domains rather than as drugs themselves.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The undruggable drivers): Dang et al., Drugging the 'undruggable' cancer targets (Nature Reviews Cancer 2017)","url":"https://doi.org/10.1038/nrc.2017.36"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["ai-drug-design"],"targets":[],"drugs":[],"companies":["isomorphic-labs","generate-biomedicines"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-undruggable-targets","b-ai-validation"],"keyPapers":["paper-dang-nat-rev-cancer"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Designed miniproteins achieve nanomolar binding to at least one disordered oncoprotein region and, when fused to a degradation domain, deplete the target in cells.","rationale":"Design methods have crossed the threshold for structured epitopes and now handle conformational ensembles; the modality is intracellular expression or conjugation, not oral dosing, which relaxes the chemistry constraints.","test":"Design and test 100 binders per target region against MYC and one fusion oncoprotein, with biophysical validation and a cell-based degradation reporter; publish successes and failures for model improvement.","maturity":"speculative","actor":"research","cost":"medium","horizonYears":7},{"id":"idea-acc-ai-first-pathology-common-cases","kind":"idea","name":"AI-first reading for high-volume common cancer diagnoses, pathologist for the exceptions","aka":[],"tldr":"Let validated AI make the first read on routine, high-volume samples like cervical smears and standard breast biopsy stains, so scarce pathologists spend their time on the difficult cases.","summary":"Pathology AI is now good enough for narrow, high-volume tasks: cervical cytology screening, prostate biopsy detection, HER2 and ER scoring on breast biopsies. In systems with a fraction of the needed pathologists, an AI-first workflow with pathologist sign-off only on flagged or discordant cases could multiply capacity. The unsolved problems are local validation on different scanners and populations, regulatory acceptance in each jurisdiction, and liability.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Most of the world has almost no cancer care): WHO fact sheet, Cancer","url":"https://www.who.int/news-room/fact-sheets/detail/cancer"}],"tags":[],"related":["idea-ai-her2-low-scoring"],"cancers":["cervical","breast-hr-positive"],"sections":[],"technologies":["digital-pathology-ai","pathology-foundation-model"],"targets":[],"drugs":[],"companies":["paige","pathai","lunit","owkin"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-global-access","b-workforce","b-ai-validation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"In a pathologist-scarce setting, an AI-first workflow will at least triple cases reported per pathologist-hour while keeping sensitivity for malignancy above 98% on prospective audit.","rationale":"AI cervical screening tools have already shown non-inferiority to cytotechnologists in several settings; the same triage logic is used for tuberculosis chest X-rays in high-burden countries.","test":"A prospective, paired-read study in two LMIC laboratories on cervical cytology and breast core biopsies: AI-first with sign-off versus full human read, measuring throughput, sensitivity, specificity, and time to report.","maturity":"early-clinical","actor":"data","cost":"medium","horizonYears":4},{"id":"idea-tr2-retraction-propagation","kind":"idea","name":"Alert guidelines and trials when a paper they rely on is retracted","aka":[],"tldr":"When a study is retracted, everything built on it should get a warning. Today, retracted cancer papers keep being cited and used for years.","summary":"Retracted papers continue to be cited, and guidelines or trial protocols that relied on them are rarely revisited. A service that maps retractions and expressions of concern (from Retraction Watch and publishers) onto the citation graph and notifies guideline bodies, trial registries and systematic reviews that cite the retracted work would close a loop that is currently open.","asOf":"2026-09-08","links":[{"label":"Retraction Watch Database","url":"https://retractionwatch.com/retraction-watch-database-user-guide/"}],"tags":[],"related":["esmo-guidelines","nccn","pubmed-europepmc"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-negative-results","b-reproducibility"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Within a year of launch, at least 80% of oncology guidelines citing a retracted paper have been notified and at least half have issued an update or statement.","rationale":"Retraction Watch's database now makes retractions machine-readable; citation graphs from OpenAlex make propagation computable. The missing piece is delivery to the people who act on the evidence.","test":"Run the service over oncology guidelines from three societies; count notifications and responses.","maturity":"speculative","actor":"data","cost":"small","horizonYears":1},{"id":"idea-moon-goals-conversation-trigger","kind":"idea","name":"Algorithm-triggered goals-of-care conversations before crisis","aka":[],"tldr":"When a prediction model says a patient has a high chance of dying within a year, their team is prompted to have a structured conversation about what matters to them, while there is still time to act on it.","summary":"Most patients with advanced cancer do not have documented conversations about goals until the final weeks. A randomised trial at Penn used a machine-learning mortality prediction to nudge oncologists, quadrupling serious illness conversations. The proposal is to make this standard: validated risk model, default prompt with a Serious Illness Conversation Guide, documentation template, and measurement of goal-concordant care and end-of-life chemotherapy use.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Patients lack understanding, navigation and agency): Basch et al., Overall survival results of a trial assessing patient-reported outcomes for symptom monitoring during routine cancer treatment (JAMA 2017)","url":"https://doi.org/10.1001/jama.2017.7156"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["penn-abramson"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-patient-voice","b-palliative"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Triggered conversations increase documented goals within 3 months of a high-risk flag from under 20% to over 50%, reduce systemic therapy in the last 14 days of life, and improve family-reported quality of dying.","rationale":"Clinicians overestimate prognosis and avoid the conversation; a neutral prompt gives permission and a time. The behaviour change has been demonstrated; the outcomes now need scale.","test":"Multi-centre stepped-wedge implementation with end-of-life quality metrics and bereaved-family surveys as primary outcomes.","maturity":"being-tested-at-scale","actor":"clinic","cost":"small","horizonYears":2},{"id":"idea-alpha-after-adc","kind":"idea","name":"Alpha radioligands after ADC failure","aka":[],"tldr":"When ADCs against a surface protein stop working because the payload no longer kills, use the same protein to deliver radiation instead.","summary":"When ADCs against a surface protein stop working because the payload no longer kills, this idea uses the same protein to deliver radiation instead. Antigen often persists after ADC failure with resistance at the payload level, so a 225Ac- or 177Lu-labelled anti-TROP2 or anti-HER2 antibody would bypass efflux, TOP1 mutations and SLFN11 loss, and crossfire would cover antigen-heterogeneous neighbours. The test is a phase 1 of a HER2 or TROP2 radioimmunoconjugate in ADC-refractory breast cancer, with antigen PET selection and dosimetry. Speculative in maturity, it complements Payload-class switching as the rule for ADC sequencing and draws on radio-antibody and radio-ADC, targeted alpha therapy and TROP2 PET.","asOf":"2026-09-04","links":[],"tags":[],"related":["idea-payload-switching"],"cancers":["tnbc","breast-hr-positive"],"sections":[],"technologies":["radioimmunotherapy","targeted-alpha-therapy","adc","trop2-pet"],"targets":["trop2","her2","b7h3"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-yarden-sliwkowski-erbb-network-nrmcb-2001"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"225Ac- or 177Lu-labelled anti-TROP2 or anti-HER2 antibodies produce responses in patients progressing on TROP2 or HER2 ADCs with retained antigen expression on PET.","rationale":"Radiation cytotoxicity is independent of drug efflux and payload-specific resistance; crossfire covers antigen-heterogeneous neighbours.","test":"Run a phase 1 of a HER2 or TROP2 radioimmunoconjugate in ADC-refractory breast cancer with antigen PET selection and dosimetry.","maturity":"speculative"},{"id":"idea-alpha-first-mhspc","kind":"idea","name":"Alpha-emitting PSMA therapy at first metastatic diagnosis","aka":[],"tldr":"If Pluvicto helps at first diagnosis, an alpha version might do more against microscopic disease, when tumour burden is smallest.","summary":"This speculative idea would give alpha-emitting PSMA therapy with actinium-225 at the first metastatic diagnosis of hormone-sensitive prostate cancer, alongside hormone therapy. Short-range alpha emission suits small-volume disease and is oxygen-independent, and early treatment avoids the PSMA heterogeneity of castration resistance; PSMAddition established beta-emitter therapy here. The hypothesis is deeper PSA nadirs and longer radiographic progression-free survival than lutetium-177 PSMA-617 at equal or lower salivary dose; salivary toxicity and actinium-225 supply are limiting. The test is a randomised phase 2 with PSMA PET-based dosimetry, salivary gland protection and the undetectable-PSA rate at one year as primary endpoint.","asOf":"2026-09-06","links":[{"label":"ClinicalTrials.gov NCT04720157: PSMAddition","url":"https://clinicaltrials.gov/study/NCT04720157"}],"tags":[],"related":[],"cancers":["prostate"],"sections":[],"technologies":["targeted-alpha-therapy","radioligand-therapy"],"targets":[],"drugs":["ac225-psma","pluvicto"],"companies":[],"institutions":[],"pathways":[],"terms":["alpha-vs-beta","dosimetry"],"trials":["psmaddition"],"people":[],"bottlenecks":[],"keyPapers":["paper-lutetium-177-vipivotide-tetrax-prostate-oncol-ther-2025","paper-lutetium-177-vipivotide-tetrax-prostate-journal-2023"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"225Ac-PSMA added to ADT + ARPI in high-volume de novo mHSPC produces deeper PSA nadirs and longer rPFS than 177Lu-PSMA-617 at equal or lower cumulative salivary dose.","rationale":"Short-range alpha emission suits small-volume disease; early treatment avoids PSMA heterogeneity that develops under castration resistance.","test":"Phase 2 randomised 225Ac-PSMA vs 177Lu-PSMA-617 in mHSPC with PSMA PET-based dosimetry, salivary gland protection, and undetectable-PSA rate at 12 months as primary.","maturity":"speculative"},{"id":"idea-acc-ambient-ai-documentation-oncology","kind":"idea","name":"Ambient AI note-taking to give oncologists back a day a week","aka":[],"tldr":"Oncologists spend hours a day typing notes. Software that listens to the consultation and drafts the note, the letter and the orders could return that time to seeing patients.","summary":"Ambient documentation tools are being adopted in primary care with reported reductions in documentation time. Oncology notes are longer and more structured (staging, regimen, cycle, toxicity grading, response), which makes them both harder and more valuable to automate. An oncology-tuned tool that also populates structured fields (mCODE-style) would improve data quality and cut clinic time, if it can be shown not to introduce clinically significant errors.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Not enough oncologists, nurses, pathologists, physicists): Yang et al., Projected supply of and demand for oncologists and radiation oncologists through 2025 (JOP 2014)","url":"https://doi.org/10.1200/JOP.2013.001319"}],"tags":[],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-workforce","b-data-silos"],"keyPapers":["paper-yang-j-oncol-pract"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Oncologists using an oncology-tuned ambient scribe will reduce documentation time per patient by at least 40% and increase weekly patient capacity by at least 10%, with a documented error rate no higher than manual notes on blinded audit.","rationale":"Documentation burden is a top driver of oncologist burnout and early retirement; recovering time is the fastest way to add capacity without new training.","test":"A randomised crossover study across 60 oncologists measuring documentation time, patient volume, burnout scores, and independent note-accuracy audits.","maturity":"early-clinical","actor":"engineering","cost":"medium","horizonYears":2},{"id":"idea-acc-clinical-officer-oncology-track","kind":"idea","name":"An 18-month oncology track for clinical officers and physician associates","aka":[],"tldr":"Training a specialist doctor takes ten years or more. Mid-level clinicians can be trained in eighteen months to run protocol-based cancer care under supervision, and there are far more of them.","summary":"Clinical officers, physician associates, and medical officers deliver most frontline care in LMIC health systems such as Malawi, Rwanda and Tanzania. A defined oncology curriculum (staging, protocol chemotherapy, toxicity management, palliative care, referral criteria) with competency assessment and a legal scope of practice would create a cadre far faster than specialist training. Malawi, Rwanda, and Tanzania have run smaller versions. The proposal is a regionally recognised qualification with a shared curriculum and examination.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Not enough oncologists, nurses, pathologists, physicists): Yang et al., Projected supply of and demand for oncologists and radiation oncologists through 2025 (JOP 2014)","url":"https://doi.org/10.1200/JOP.2013.001319"}],"tags":[],"related":["idea-acc-nurse-led-chemotherapy-units"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-workforce","b-global-access"],"keyPapers":["paper-yang-j-oncol-pract"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Districts staffed by oncology-trained clinical officers will double the number of patients receiving protocol-based treatment within two years, with toxicity-related mortality no higher than at specialist-staffed centres for the same regimens.","rationale":"Task-shifting to mid-level cadres delivered antiretroviral scale-up, caesarean sections, and anaesthesia across Africa with outcomes equivalent to physician care in trials.","test":"A regional cohort of 100 trainees with pre-post competency testing and a two-year outcome audit at their posting sites compared with matched sites without trainees.","maturity":"early-clinical","actor":"policy","cost":"medium","horizonYears":3},{"id":"idea-fund-abbreviated-pathway-me-too-biologics","kind":"idea","name":"An abbreviated approval path for follow-on antibodies within a validated class","aka":[],"tldr":"Once a class of antibody such as PD-1 blockers is proven, later copies could be approved on smaller trials showing equivalence, forcing price competition and freeing patients and money for genuinely new drugs.","summary":"For mechanistic classes with multiple approved agents and well-understood pharmacology (anti-PD-1, anti-CD20, anti-HER2), regulators create a pathway between biosimilar approval and a full new-drug approval: approval based on pharmacodynamic equivalence and a single non-inferiority efficacy trial against an approved class member, with pricing expected to follow biosimilar dynamics. This ends the wasteful situation in which each of a dozen PD-1 antibodies runs its own placebo- or chemotherapy-controlled phase 3 in populations already known to benefit, while giving payers real competition within class. Capital that cannot earn novel-drug returns on copies moves elsewhere.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Incentives reward me-too drugs and marginal gains): Upadhaya et al., PD1/PDL1 inhibitor clinical trial landscape (Nat Rev Drug Discov 2022)","url":"https://doi.org/10.1038/d41573-022-00030-4"}],"tags":[],"related":["idea-fund-benefit-indexed-exclusivity","idea-fund-head-to-head-mandate"],"cancers":[],"sections":[],"technologies":[],"targets":["pd1","cd20","her2"],"drugs":["pembrolizumab","nivolumab","trastuzumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-incentive-misalignment","b-drug-pricing","b-trial-design"],"keyPapers":["paper-upadhaya-nat-rev-drug-discov"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"An abbreviated class pathway reduces net prices of the affected class by at least 30% within three years of the first abbreviated approval and reduces the number of full-scale placebo-controlled phase 3 trials of later-in-class agents in the class.","rationale":"Biosimilar pathways cut prices for rituximab and trastuzumab substantially in Europe; several later PD-1 antibodies approved in China are already priced far below Western incumbents. The clinical pharmacology of these classes is well enough understood that repeating full development adds little knowledge.","test":"Regulator consultation and a pilot pathway for one class (anti-PD-1) with defined equivalence criteria, tracking approvals, trial designs and net prices over four years.","maturity":"speculative","actor":"regulator","cost":"small","horizonYears":4},{"id":"idea-reg-pd1-biosimilar-advance-commitment","kind":"idea","name":"An advance market commitment for PD-1 biosimilars for lower-income countries","aka":[],"tldr":"Immunotherapy patents start expiring around 2028. Guaranteeing in advance to buy cheap copies for poorer countries would make sure manufacturers build the capacity.","summary":"Pembrolizumab and nivolumab lose their core patent protection in the largest markets from about 2028; biosimilar developers are targeting high-income markets first, and LMIC supply may lag by years as it did for trastuzumab. Gavi's pneumococcal advance market commitment showed that a guaranteed purchase at a ceiling price can accelerate manufacturing investment for poorer markets. The proposal is a donor- and government-backed commitment to buy a defined volume of WHO-prequalified PD-1 biosimilars for LMIC programmes at a ceiling price (for example under $500 per dose) from 2028, with WHO prequalification and pooled procurement handling quality and distribution.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Prices and value): Prasad, De Jesús & Mailankody, The high price of anticancer drugs: origins, implications, barriers, solutions (Nat Rev Clin Oncol 2017)","url":"https://doi.org/10.1038/nrclinonc.2017.31"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":["pd1"],"drugs":["pembrolizumab","nivolumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-drug-pricing","b-global-access"],"keyPapers":["paper-prasad-nat-rev-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"The commitment leads to at least two prequalified PD-1 biosimilars being supplied to LMIC programmes within 18 months of patent expiry, at prices under a tenth of current high-income list prices, treating more than 100,000 additional patients a year within five years.","rationale":"Checkpoint inhibitors have the widest indication range of any oncology class, low marginal manufacturing cost and a demonstrated survival benefit in cancers common in LMICs; without a demand signal, manufacturers will serve the highest-margin markets first.","test":"Structure the commitment with two or three anchor funders, announce it three years before patent expiry, and track prequalification filings, supply volumes and prices against the trastuzumab biosimilar precedent.","maturity":"speculative","actor":"philanthropy","cost":"large","horizonYears":4},{"id":"idea-tr2-liquid-biopsy-challenge","kind":"idea","name":"An annual blinded shoot-out for liquid biopsy tests","aka":[],"tldr":"Once a year, send the same blinded blood samples to every company selling a tumour-DNA test and publish how each performed.","summary":"The FDA-led SEQC2 project compared ctDNA assays on reference samples once. Making this an annual, blinded round with contrived and clinical samples spanning variant types and allele fractions, published with assay names, would create continuous pressure on performance and detect degradation when assays change versions. Participation would be a condition of regulatory clearance or reimbursement.","asOf":"2026-09-08","links":[{"label":"FDA SEQC2 project (page moved; nearest live section)","url":"https://www.fda.gov/science-research/bioinformatics-tools/"}],"tags":[],"related":["guardant-health","natera","grail","idea-tr2-ctdna-reference-plasma"],"cancers":[],"sections":[],"technologies":["liquid-biopsy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["ctdna","vaf"],"trials":[],"people":[],"bottlenecks":["b-biomarker-validation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Annual publication will drive the median sensitivity at 0.5% allele fraction across participating assays up by at least ten percentage points over three rounds, and will identify at least one assay whose performance changed with a version update.","rationale":"Continuous, public benchmarking works in machine learning and in proficiency testing; a single published comparison quickly goes out of date.","test":"Run the first round with ten assays; publish; repeat annually and track performance trajectories.","maturity":"early-clinical","actor":"regulator","cost":"small","horizonYears":1},{"id":"idea-fund-white-space-map","kind":"idea","name":"An annual map of high-burden questions that nobody is funding","aka":[],"tldr":"Mine grant databases and the literature to find cancer types and questions with heavy burden and zero active projects, then publish the list so funders and scientists can go there.","summary":"Cross the burden matrix (cancer type by stage by question: prevention, detection, metastasis, resistance, supportive care) against active grants, registered trials and recent publications to identify 'white space': cells with high burden and little or no activity. Publish a ranked list each year with suggested first experiments, and pair it with a dedicated call. Language models can classify grant abstracts and trial registrations at scale, which makes the map cheap to maintain.","asOf":"2026-09-08","links":[{"label":"Illuminating the Druggable Genome","url":"https://commonfund.nih.gov/idg"}],"tags":[],"related":["clinicaltrials-gov","open-targets","pubmed-europepmc","idea-fund-dollars-per-death-dashboard"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-funding-allocation","b-negative-results"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Publishing a white-space map with a linked call raises the number of funded projects in the ten highest-burden empty cells by at least fivefold within three years, compared with equally empty cells not highlighted.","rationale":"Funding follows visibility; the Open Targets and Illuminating the Druggable Genome programmes showed that simply cataloguing understudied proteins and offering targeted money moved researchers into them. The same mechanism should work for clinical questions.","test":"Build the map for one country from public grant and trial data; randomise which white-space cells are highlighted in a call and compare subsequent application volume between highlighted and control cells.","maturity":"speculative","actor":"data","cost":"small","horizonYears":2},{"id":"idea-fund-antitrust-safe-harbour","kind":"idea","name":"An antitrust safe harbour for cross-company combination trials and data pooling","aka":[],"tldr":"Companies say competition law stops them coordinating on combination trials and sharing failure data. A clear legal safe harbour for defined pro-patient collaborations would remove that excuse.","summary":"Competition authorities issue guidance or a block exemption, as the EU has for research and development agreements and as the US did for certain healthcare collaborations, that explicitly protects defined oncology collaborations: joint combination trials, sharing of safety and negative-efficacy data, pooled control arms, pre-competitive target validation and standard combination agreements, subject to transparency conditions (registration of the collaboration, publication of results). Companies frequently cite antitrust uncertainty as a reason not to share data or coordinate trials; whether that is a real barrier or a convenient one, a safe harbour removes it and lets other collaboration proposals proceed.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Secrecy and intellectual property block collaboration): Danchev et al., Evaluation of data sharing after implementation of the ICMJE data sharing statement requirement (JAMA Netw Open 2021)","url":"https://doi.org/10.1001/jamanetworkopen.2020.33972"}],"tags":[],"related":["idea-fund-compulsory-combination-access","idea-fund-trial-data-trust","idea-fund-combination-patent-pool"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-ip-collaboration"],"keyPapers":["paper-danchev-jama-netw-open"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"After the safe harbour, the number of registered multi-company oncology collaborations involving data sharing or joint trials rises by at least half within two years, and companies stop citing antitrust risk in surveys of collaboration barriers.","rationale":"The EU R&D block exemption and US National Cooperative Research and Production Act show that legal clarity increases pre-competitive collaboration; regulators including the FDA have encouraged industry data pooling (for example on immune-related adverse events) but companies report legal caution.","test":"Survey collaboration barriers before and after issuing guidance in one jurisdiction; count registered collaborations meeting the safe-harbour criteria over two years.","maturity":"speculative","actor":"policy","cost":"small","horizonYears":2},{"id":"idea-moon-supportive-care-arpa","kind":"idea","name":"An ARPA-style programme to develop supportive-care drugs nobody else will","aka":[],"tldr":"A supportive-care ARPA would be a well-funded, milestone-driven agency that develops drugs for nausea, nerve damage, mouth sores, fatigue and brain fog from cancer treatment, which the market has largely ignored.","summary":"Supportive-care drug development has stalled: the last major antiemetic class (NK1 antagonists) is over twenty years old, there is no approved preventive for chemotherapy-induced neuropathy, and fatigue and cognitive impairment have no pharmacological standard. The proposal is a dedicated programme (public or philanthropic, ARPA-H style) funding target discovery, repurposing screens and pragmatic trials of supportive-care agents, with pull incentives (advance purchase, priority review vouchers) for approvals.","asOf":"2026-09-08","links":[{"label":"ARPA-H","url":"https://arpa-h.gov/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol","b-cachexia-supportive"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A ten-year, well-funded programme delivers at least three new approved supportive-care agents and measurably reduces dose reductions and discontinuations for toxicity across common regimens.","rationale":"Supportive-care drugs are generics-priced and off-patent-adjacent, so private investment is weak although the population is enormous and the endpoints are fast. Focused public programmes have succeeded where markets failed (antibiotics, neglected diseases).","test":"Fund a first cohort of five programmes (neuropathy prevention, mucositis, cachexia, fatigue, cognition) with 3-year go/no-go milestones; success is two reaching phase 3 with positive phase 2 signals.","maturity":"speculative","actor":"philanthropy","cost":"large","horizonYears":6},{"id":"idea-acc-universal-asynchronous-second-opinion","kind":"idea","name":"An asynchronous expert second opinion for every new advanced-cancer diagnosis","aka":[],"tldr":"Every patient newly diagnosed with advanced cancer would have their records reviewed by an expert centre within a week, without travelling. The review often changes the plan.","summary":"Second-opinion studies consistently show that expert review changes diagnosis or management in a substantial minority of cases, especially in pathology and molecular interpretation. Providing an asynchronous, record-based expert review for all new stage IV diagnoses, funded by payers and delivered by accredited centres, would spread expertise without moving patients. AI could pre-structure the record to reduce reviewer time.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Fragmented care and guideline gaps): Hanna et al., Mortality due to cancer treatment delay: systematic review and meta-analysis (BMJ 2020)","url":"https://doi.org/10.1136/bmj.m4087"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-care-fragmentation","b-knowledge-diffusion","b-trial-enrolment"],"keyPapers":["paper-hanna-bmj"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Universal second opinion will change management in at least 15% of advanced cancer cases and increase enrolment in appropriate trials and use of targeted therapy in eligible patients.","rationale":"The value of second opinion is established; the gap is access, which is inequitably distributed toward well-informed patients near academic centres.","test":"A payer pilot in one region offering review to all new stage IV patients, measuring change in management, trial enrolment, and patient satisfaction.","maturity":"speculative","actor":"payer","cost":"medium","horizonYears":3},{"id":"idea-reg-target-trial-emulation-pipeline","kind":"idea","name":"An automated pipeline emulating trials of every common drug against every cancer","aka":[],"tldr":"Millions of people take common drugs and some get cancer. Running standardised analyses across whole-country records could rank which old drugs deserve a real trial.","summary":"Nordic registries, UK CPRD and OpenSAFELY, US VA and Medicare, and Korean and Taiwanese national databases together cover hundreds of millions of people. Target trial emulation with active-comparator new-user designs, pre-registered protocols and negative-control outcomes can screen drug-cancer pairs systematically rather than one paper at a time. The proposal is an open, federated pipeline that runs a common protocol across databases for a defined library of drugs and cancer outcomes, publishes all results (including nulls) with bias diagnostics, and feeds a public prioritisation list for the repurposing fund.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (No incentive to repurpose cheap drugs): Pantziarka et al., The Repurposing Drugs in Oncology (ReDO) Project (ecancer 2014)","url":"https://doi.org/10.3332/ecancer.2014.442"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["real-world-evidence"],"trials":[],"people":[],"bottlenecks":["b-generic-repurposing","b-real-world-evidence"],"keyPapers":["paper-pantziarka-ecancermedicalscience"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"The pipeline identifies at least five drug-cancer pairs with concordant protective associations across three or more independent databases and negative-control checks within two years, and at least one enters a randomised trial.","rationale":"Single-database observational studies have produced many false leads; federated, pre-registered, multi-database analysis with shared code is the only way to separate robust signals from artefacts at scale.","test":"Build the pipeline for 50 drugs and 10 cancers across four databases, publish concordance results, and compare with known positives (aspirin-colorectal) and known negatives (metformin-breast).","maturity":"preclinical-evidence","actor":"data","cost":"medium","horizonYears":3},{"id":"idea-acc-electronic-frailty-index-oncology","kind":"idea","name":"An automatic electronic frailty index inside the oncology record","aka":[],"tldr":"Frailty is the strongest predictor of who will be harmed by treatment, but it is rarely measured. Software can estimate it automatically from existing records and flag patients who need a closer look.","summary":"Electronic frailty indices derived from coded diagnoses, prescriptions, and utilisation are used in primary care in England and predict outcomes well. An oncology version, computed automatically at referral and displayed with the staging information, would identify patients who should have a full geriatric assessment and would allow frailty-stratified outcome reporting. It requires validation against clinical frailty scales and treatment outcomes.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Older and multimorbid patients are excluded and undertreated): Mohile et al., Evaluation of geriatric assessment and management on toxic effects of cancer treatment (GAP70+, Lancet 2021)","url":"https://doi.org/10.1016/S0140-6736(21)01789-X"}],"tags":[],"related":["idea-acc-geriatric-assessment-by-default"],"cancers":[],"sections":["ai-computation"],"technologies":["geriatric-assessment"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-aging-comorbidity","b-data-silos"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"An automated frailty index will predict grade 3 or higher toxicity and 90-day mortality after systemic therapy with discrimination at least as good as clinician judgement, and will increase geriatric assessment referrals among flagged patients.","rationale":"Automated indices remove the workload barrier that limits formal screening and enable population-level monitoring of undertreatment and overtreatment.","test":"Derive and validate the index in two health systems against toxicity and survival, then a pragmatic trial of displaying it versus not on assessment referrals and outcomes.","maturity":"early-clinical","actor":"data","cost":"small","horizonYears":2},{"id":"idea-prev-ebv-vaccine","kind":"idea","name":"An Epstein-Barr virus vaccine to prevent nasopharyngeal cancer and lymphomas","aka":[],"tldr":"EBV infects almost everyone and causes nasopharyngeal cancer, some lymphomas and some stomach cancers. A vaccine given before infection could remove those cancers.","summary":"Epstein-Barr virus infects almost everyone and causes nasopharyngeal cancer, some lymphomas and some stomach cancers, so this idea accelerates development of an EBV vaccine given before infection, with infection prevention and infectious mononucleosis as first endpoints and later deployment in high-incidence nasopharyngeal cancer regions. Moderna's mRNA-1189 and the NIH gp350 nanoparticle vaccine are in early trials, and HPV and HBV vaccines prove that preventing a viral infection prevents its cancers. The test is a phase 2 infection-prevention trial in EBV-seronegative adolescents. At early-clinical maturity it addresses the bottleneck Prevention we already have is not deployed and links to head and neck cancer, Hodgkin lymphoma and gastric cancer.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Prevention we already have is not deployed): Islami et al., Proportion of cancer attributable to modifiable risk factors (CA 2018)","url":"https://doi.org/10.3322/caac.21440"}],"tags":[],"related":[],"cancers":["head-and-neck","hodgkin-lymphoma","gastric"],"sections":["prevention"],"technologies":[],"targets":[],"drugs":[],"companies":["moderna"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption"],"keyPapers":["paper-islami-ca-cancer-j-clin"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"An EBV vaccine preventing at least 70% of primary infection in adolescents reduces EBV-associated cancers by a similar fraction in vaccinated cohorts over decades.","rationale":"HPV and HBV vaccines prove the model; EBV-related cancers exceed 200,000 cases a year.","test":"Run a phase 2 infection-prevention trial in EBV-seronegative adolescents.","maturity":"early-clinical","actor":"industry","cost":"large","horizonYears":15},{"id":"idea-fund-surgical-ai-robotics-evaluation","kind":"idea","name":"An independent evaluation unit for surgical robots and AI, paid on evidence","aka":[],"tldr":"Hospitals buy multi-million-dollar surgical robots and AI tools with little proof they help patients. An independent body would run the comparative trials, and payers would only pay premiums for what is shown to work.","summary":"A publicly-funded evaluation unit, analogous to a health technology assessment body but with the capacity to sponsor randomised and registry-based comparisons, for surgical robotics, intraoperative AI (anatomy recognition, margin prediction, skill assessment) and autonomous surgical functions in cancer surgery. Reimbursement premiums for these technologies would be conditional on participation in unit-led evaluations, with results published. Robotic surgery has diffused for two decades with few randomised trials, and surgical AI is following the same path; the drug world's requirement for evidence before payment is absent here.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Surgery and radiotherapy cure most, get least): Sullivan et al., Global cancer surgery (Lancet Oncology Commission 2015)","url":"https://doi.org/10.1016/S1470-2045(15)00223-5"}],"tags":[],"related":["idea-fund-device-technique-registry","idea-fund-surgical-video-registry","idea-fund-adaptive-radiotherapy-evidence"],"cancers":[],"sections":[],"technologies":["robotic-surgery","fluorescence-guided-surgery"],"targets":[],"drugs":[],"companies":["intuitive-surgical"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-surgery-radiation-innovation","b-ai-validation"],"keyPapers":["paper-sullivan-lancet-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"An evaluation unit with conditional-payment leverage generates randomised or high-quality comparative evidence for at least ten surgical robotic or AI applications within four years and leads to at least two adoption decisions being reversed or restricted on the basis of that evidence.","rationale":"Where randomised trials of robotic surgery have been done (ROLARR for rectal cancer, RAZOR for cystectomy) they showed no oncological advantage and much higher cost; those trials were run without any systematic mechanism. Coverage with evidence development has made trials happen for cardiac devices and proton therapy.","test":"Establish the unit, link premium reimbursement of two technologies to enrolment in its comparative studies, and measure evidence generated and adoption changes over four years.","maturity":"speculative","actor":"payer","cost":"large","horizonYears":4},{"id":"idea-moon-hype-index","kind":"idea","name":"An independent hype index grading cancer press releases and news stories","aka":[],"tldr":"Rate every cancer breakthrough story and press release for spin, using set criteria, and publish the scores so journalists, institutions and readers can see who overstates.","summary":"Spin in abstracts and press releases is documented and propagates into news coverage and patient expectations; HealthNewsReview.org showed independent grading is feasible before it closed for lack of funding. The proposal is a sustainably funded service that grades press releases from journals, institutions and companies on a published rubric (absolute versus relative numbers, harms, cost, stage of evidence, independent comment), publishes an institution-level hype index, and provides a plain-language re-statement of each finding.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Misinformation and unproven therapies): Johnson et al., Cancer misinformation and harmful information on Facebook and other social media (JNCI 2022)","url":"https://doi.org/10.1093/jnci/djab141"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-misinformation","b-incentive-misalignment"],"keyPapers":["paper-johnson-j-natl-cancer-inst"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Published hype scores reduce spin in subsequent press releases from graded institutions and reduce exaggerated claims in downstream news coverage.","rationale":"Reputational feedback changes institutional behaviour; the rubric exists and the grading cost is low.","test":"Grade all cancer press releases from the top 50 institutions for a year and publish; compare spin metrics in year two against ungraded institutions.","maturity":"early-clinical","actor":"research","cost":"small","horizonYears":1},{"id":"idea-tr1-surrogate-validation-programme","kind":"idea","name":"An independent programme that validates surrogate endpoints, setting by setting","aka":[],"tldr":"Trials often measure a stand-in for survival, such as time until the cancer grows on scans. An independent body would test, for each cancer and treatment type, whether the stand-in actually predicts survival, and publish the answer.","summary":"A standing, publicly funded consortium performs individual-patient-data meta-analyses of completed randomised trials to quantify trial-level surrogacy (correlation of treatment effects on PFS, pCR, MRD, ORR with effects on OS or QoL) by disease setting and drug class, publishes surrogate threshold effects, and maintains a public register of validated, unvalidated and refuted surrogates. Regulators reference the register when accepting surrogate-based endpoints.","asOf":"2026-09-08","links":[{"label":"FDA Oncology Center of Excellence: Project Endpoint","url":"https://www.fda.gov/about-fda/oncology-center-excellence/project-endpoint"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["esmo","asco"],"pathways":[],"terms":["pfs","os","pcr","mrd","orr","accelerated-approval"],"trials":[],"people":[],"bottlenecks":["b-trial-design","b-biomarker-validation"],"keyPapers":["paper-reproducibility-project-cancer-biology-elife-2021"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Where the register rates a surrogate as weak, requiring OS or QoL co-primary endpoints will not slow approval by more than a year on average, and post-marketing withdrawals for lack of benefit will fall.","rationale":"Systematic reviews have found trial-level surrogacy of PFS for OS is strong in some settings and poor in others, yet the same endpoint is accepted across settings. Data sharing platforms now make IPD meta-analysis feasible at scale.","test":"Fund the programme for three cancers with the most surrogate-based approvals and compare regulators' endpoint decisions before and after the register exists.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":4},{"id":"idea-moon-independent-replication-institute","kind":"idea","name":"An independent replication institute that re-tests key preclinical cancer findings before trials","aka":[],"tldr":"Many cancer lab results cannot be reproduced, and trials built on them fail. Fund an independent institute that re-runs important experiments before anyone spends millions on humans.","summary":"The Reproducibility Project: Cancer Biology found that most high-profile preclinical results replicated only partially or not at all. Trials and companies are built on unreplicated findings. The proposal is a funded, independent replication institute with standing capacity in the common cancer model systems, which re-tests findings prioritised by their influence on planned trials or investments, publishes all results, and issues a replication grade that funders, investors and ethics committees can require before first-in-human studies.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Preclinical results do not reproduce): Errington et al., Investigating the replicability of preclinical cancer biology (eLife 2021)","url":"https://doi.org/10.7554/eLife.71601"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["pdx-models","organoids"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-reproducibility","b-translational-valley"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Replication grading before phase 1 reduces the rate of early trials terminated for lack of efficacy and shifts investment toward findings that replicate.","rationale":"Independent replication is the cheapest insurance against the most expensive failures; it is not done because nobody owns it and careers do not reward it.","test":"Grade 50 findings underlying planned trials; follow the trials for three years and compare outcomes of high- and low-grade findings.","maturity":"early-clinical","actor":"philanthropy","cost":"medium","horizonYears":3},{"id":"idea-prev-indolent-lesion-nomenclature-body","kind":"idea","name":"An international body to rename indolent lesions so 'cancer' means something","aka":[],"tldr":"Some things called cancer, such as low-grade prostate lesions, almost never spread. An expert body could reclassify them, as cervical precancer was, so fewer people are overtreated.","summary":"Cervical CIN and bladder PUNLMP are precedents for moving low-risk lesions out of the carcinoma category. Propose a WHO/IARC-convened classification group with explicit criteria (lifetime metastatic risk under 1% untreated) and a schedule to review Gleason 6, papillary microcarcinoma, low-grade DCIS, small renal masses, and Barrett's low-grade dysplasia.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Overdiagnosis and false alarms): Welch & Black, Overdiagnosis in cancer (JNCI 2010)","url":"https://doi.org/10.1093/jnci/djq099"}],"tags":[],"related":[],"cancers":["prostate","thyroid"],"sections":["early-detection"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["iarc"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-overdiagnosis"],"keyPapers":["paper-welch-j-natl-cancer-inst"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Reclassification reduces active treatment of the reclassified lesions by at least 40% within five years without a measurable increase in cancer-specific mortality.","rationale":"Words drive fear and treatment; PUNLMP shows the profession can do this.","test":"Pre/post analysis after WHO Classification of Tumours reclassification for one lesion type, Gleason 6 first.","maturity":"speculative","actor":"policy","cost":"small","horizonYears":5},{"id":"idea-data-paediatric-rwe-consortium","kind":"idea","name":"An international consortium pooling the outcome of every treated child with cancer","aka":[],"tldr":"Childhood cancers are rare, so no one country sees enough cases. Pool the treatment and outcome of every child treated anywhere into one governed dataset.","summary":"Paediatric oncology already treats most children on or according to cooperative-group protocols, with structured data. Linking cooperative-group databases (COG, SIOP Europe, and LMIC networks) into one federated real-world resource, including children treated off-protocol and in LMICs, would allow toxicity, late effects and rare subtype questions to be answered globally. The proposal funds the governance, common data model and federation.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Weak real-world evidence and registries): Gyawali, Hey & Kesselheim, Assessment of the clinical benefit of cancer drugs receiving accelerated approval (JAMA Intern Med 2019)","url":"https://doi.org/10.1001/jamainternmed.2019.0462"}],"tags":[],"related":[],"cancers":["neuroblastoma","sarcoma"],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":["childrens-oncology-group"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-real-world-evidence","b-rare-cancers","b-data-silos"],"keyPapers":["paper-gyawali-jama-intern-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A pooled paediatric resource covering more than 80 percent of treated children in participating countries will answer rare-subtype and late-effect questions with cohorts five times larger than any current group and will be used to design the next generation of risk-adapted protocols.","rationale":"Paediatric oncology's cooperative structure is unique; the data exist in silos separated by group and continent, not by lack of standardisation.","test":"Federate COG and SIOP databases for two diseases (neuroblastoma, Ewing sarcoma); answer three pre-registered questions and report the marginal value of pooling.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":4},{"id":"idea-reg-net-price-transparency-registry","kind":"idea","name":"An international registry of real (net) cancer drug prices paid by public payers","aka":[],"tldr":"Countries negotiate secret discounts, so nobody knows what anyone actually pays for a cancer drug. Sharing real prices between public buyers would strengthen every negotiation.","summary":"Confidential rebates mean list prices are fiction and payers negotiate blind, a situation that the WHO Fair Pricing Forum and the Oslo Medicines Initiative have identified as one of the main drivers of high prices. The proposal is a treaty-level or coalition arrangement in which public payers deposit net prices per oncology product into a secure registry visible to other participating payers (not to the public or industry), with aggregate transparency published annually. Beneluxa and the Nordic Pharmaceutical Forum already share some information.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Prices and value): Prasad, De Jesús & Mailankody, The high price of anticancer drugs: origins, implications, barriers, solutions (Nat Rev Clin Oncol 2017)","url":"https://doi.org/10.1038/nrclinonc.2017.31"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-drug-pricing","b-data-silos"],"keyPapers":["paper-prasad-nat-rev-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Payers with access to the registry achieve net prices at least 10% lower than non-participants for the same products within three years, and the dispersion of net prices across similar-income countries narrows.","rationale":"Information asymmetry favours the seller in every negotiation; shared price intelligence is standard practice among large purchasers in other sectors and is the cheapest lever payers have.","test":"Establish the registry among five to ten European payers for oncology products, and compare their net price trajectories with matched non-participating payers using confidential data audited by a neutral party.","maturity":"speculative","actor":"payer","cost":"small","horizonYears":3},{"id":"idea-fund-combination-patent-pool","kind":"idea","name":"An oncology patent pool for combination trials across companies","aka":[],"tldr":"Companies would put their cancer drugs into a shared licensing pool so that any qualified investigator can test combinations of drugs from different owners under one standard agreement, with royalties split by a fixed formula.","summary":"A voluntary pool, administered by a neutral body on the model of the Medicines Patent Pool and the MPEG patent pools, in which participating companies grant a standard non-exclusive licence for their approved and late-stage oncology agents to be used in combination trials sponsored by academic groups, non-profits or other pool members, with pre-agreed terms for drug supply, data rights, publication and downstream royalty sharing if a combination is approved. Today each combination requires a bespoke negotiation that can take longer than the trial; pooled terms cut that to weeks. Regulators would recognise pool trials as acceptable for combination labelling.","asOf":"2026-09-08","links":[{"label":"Medicines Patent Pool","url":"https://medicinespatentpool.org/"}],"tags":[],"related":["idea-fund-standard-combination-agreement","idea-fund-compulsory-combination-access","idea-fund-neutral-platform-sponsor","adc-plus-io","radiation-plus-io"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-ip-collaboration","b-combination-space"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A pool with at least ten participating companies doubles the number of registered cross-company combination trials involving pooled agents within three years and reduces median contract negotiation time for such trials from over a year to under three months.","rationale":"The Medicines Patent Pool has licensed dozens of HIV, hepatitis C and tuberculosis products through standard terms; standards-essential patent pools show competing firms can agree fixed royalty splits. Combination therapy is where most oncology benefit now comes from and where inter-company friction is greatest.","test":"Convene five companies and two academic networks to sign pool terms for a defined set of agents; measure trials initiated and negotiation time against the same companies' prior bilateral combination agreements.","maturity":"speculative","actor":"industry","cost":"medium","horizonYears":3},{"id":"idea-bio1-collateral-sensitivity-atlas","kind":"idea","name":"An open atlas of collateral sensitivity for every approved targeted drug","aka":[],"tldr":"When a tumour evolves resistance to one drug, it sometimes becomes weaker against another. Map these trade-offs systematically so doctors can pick the next drug to exploit them.","summary":"Collateral sensitivity is well characterised in antibiotics and shown in a few oncology examples (MEK-inhibitor resistance sensitising to certain agents, ABL inhibitor rotation in CML). A systematic programme would evolve resistance to each approved targeted agent in dozens of models, screen the resistant derivatives against the full pharmacopoeia, and publish a public sensitivity map to inform sequencing trials.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Tumour heterogeneity and clonal evolution): Gerlinger et al., Intratumor heterogeneity and branched evolution (NEJM 2012)","url":"https://doi.org/10.1056/NEJMoa1113205"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["functional-drug-testing","crispr-screens"],"targets":[],"drugs":[],"companies":[],"institutions":["broad-institute"],"pathways":[],"terms":["resistance"],"trials":[],"people":[],"bottlenecks":["b-tumor-heterogeneity","b-resistance","b-combination-space"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"For most approved targeted agents, at least one collateral sensitivity with a greater than three-fold shift will be reproducible across models and will translate into a sequencing rule that prolongs second-line response in a trial.","rationale":"Resistance carries costs. Antibiotic collateral sensitivity maps have already guided cycling regimens; oncology has the models and drugs but has never done the systematic screen.","test":"Two-year screen across 20 drugs and 200 models with independent replication of top hits; then a randomised second-line sequencing trial in the setting with the strongest signal.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":4},{"id":"idea-moon-open-pro-data-commons","kind":"idea","name":"An open commons of patient-reported outcome data from cancer trials","aka":[],"tldr":"Pool the side-effect and quality-of-life data patients report in trials into one open database so regimens can be compared honestly and models can be built.","summary":"PRO data from trials sit in sponsor archives and are rarely shared or comparable. Project Data Sphere and Vivli show that trial data sharing is feasible. The proposal is a dedicated PRO commons with standardised instruments and formats (PRO-CTCAE, EORTC QLQ-C30, PROMIS), mandatory deposition for publicly funded trials and incentives for industry, and tools for cross-trial comparison of symptom burden by regimen and patient characteristics.","asOf":"2026-09-08","links":[{"label":"Project Data Sphere","url":"https://www.projectdatasphere.org/"},{"label":"Vivli","url":"https://vivli.org/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol","b-data-silos"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Within three years the commons contains PRO data from over 100 trials and supports at least ten published cross-regimen tolerability comparisons that inform guidelines and decision aids.","rationale":"Tolerability is only meaningful in comparison, and comparison requires pooled, standardised data. The infrastructure for sharing trial data exists; PROs are simply not prioritised.","test":"Seed the commons with data from cooperative-group trials and one industry partner; measure deposition rates, reuse and citations.","maturity":"speculative","actor":"data","cost":"medium","horizonYears":3},{"id":"idea-moon-open-degrader-consortium","kind":"idea","name":"An open degrader consortium against every undruggable driver transcription factor","aka":[],"tldr":"Cancer's most important drivers, such as MYC and mutant p53, cannot be blocked with normal drugs. Pool effort and share results openly to build molecules that destroy them instead.","summary":"Targeted protein degradation (PROTACs, molecular glues) has produced clinical candidates for previously undruggable proteins, but efforts against the hardest targets are fragmented and duplicated under secrecy. Structural Genomics Consortium-style open science produced chemical probes for hundreds of proteins. The proposal is an open consortium with industry, academic and philanthropic members that generates and releases ligands, degraders, ternary complex structures and assays for the ten highest-value undruggable drivers (MYC, mutant TP53 variants, beta-catenin, KRAS G12D and rarer variants, fusion oncoproteins), with a pre-agreed rule that clinical candidates may be developed by any member.","asOf":"2026-09-08","links":[{"label":"Open Targets","url":"https://www.opentargets.org/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["protac-degrader","ai-drug-design"],"targets":["tp53","kras"],"drugs":[],"companies":["arvinas","kymera","monte-rosa"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-undruggable-targets","b-ip-collaboration"],"keyPapers":["paper-vogelstein-surfing-p53-network-nature-2000"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Open pooling delivers clinical candidates against at least three undruggable drivers within six years, faster than any single closed programme has achieved for the same targets.","rationale":"Pre-competitive sharing of probes and structures has repeatedly accelerated target validation; the largest risks in these targets are scientific, not commercial, so secrecy mainly buys duplication.","test":"Launch with three targets and five members; success is an open, validated in vivo-active degrader for at least one target within three years.","maturity":"preclinical-evidence","actor":"research","cost":"large","horizonYears":7},{"id":"idea-tr2-synergy-ranking-engine","kind":"idea","name":"An open engine that ranks every drug pair by predicted synergy before anyone runs a trial","aka":[],"tldr":"Use existing cell-line and organoid data to score thousands of drug pairs, publish the ranking openly, and only test the top of the list in people.","summary":"DepMap dependency screens, the NCI ALMANAC pairwise matrix and published organoid drug-response sets contain far more combination signal than has been mined. A public model that predicts synergy and, critically, therapeutic window (tumour versus normal-cell toxicity) for each pair in each molecular context would give trialists a prioritised shortlist. Models should be scored prospectively against every new combination readout.","asOf":"2026-09-08","links":[{"label":"DepMap portal","url":"https://depmap.org/portal/"},{"label":"NCI ALMANAC","url":"https://dtp.cancer.gov/ncialmanac"},{"label":"DREAM Challenges","url":"https://dreamchallenges.org/"}],"tags":[],"related":["depmap","drugbank-chembl","idea-organoid-guided-adc"],"cancers":[],"sections":[],"technologies":["crispr-screens","organoids","ai-drug-design"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-combination-space","b-preclinical-models"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Combinations in the top decile of the published ranking will show randomised phase 2 success (meeting primary endpoint) at least twice as often as combinations chosen by conventional mechanistic argument.","rationale":"The DREAM AstraZeneca-Sanger synergy challenge showed predictive signal in cell lines. NCI ALMANAC identified bortezomib plus clofarabine from a systematic screen. The failure has been that rankings are not published, not maintained and not scored against outcomes.","test":"Publish rankings for all pairs of approved oncology drugs; register predictions; score them against every randomised combination readout over three years, reporting calibration publicly.","maturity":"preclinical-evidence","actor":"data","cost":"medium","horizonYears":3},{"id":"idea-fund-academic-adc-bispecific-platform","kind":"idea","name":"An open engineering platform for academic ADCs and bispecifics","aka":[],"tldr":"Academic labs find new tumour targets but cannot turn an antibody into an antibody-drug conjugate or a bispecific without licensed linker and payload technology. A shared platform would provide that at no cost for first trials.","summary":"A publicly-funded platform holding licences (or developing its own patent-free versions) for linker-payload chemistries, site-specific conjugation, bispecific formats and CAR constructs, offered royalty-free to academic teams for research and first-in-human studies, with commercial terms triggered only on licensing to a company. Paired with GMP manufacturing at translational institutes, this lets academic centres test conjugates against novel or rare-cancer antigens that no company will prioritise. The Structural Genomics Consortium's open chemical probes and the IAVI/Neutralizing Antibody Center model for HIV antibodies are precedents for open engineering infrastructure.","asOf":"2026-09-08","links":[{"label":"Structural Genomics Consortium","url":"https://www.thesgc.org/"}],"tags":[],"related":["idea-fund-translational-institutes-gmp","idea-fund-shared-personalised-therapy-gmp"],"cancers":[],"sections":[],"technologies":["adc","bispecific-antibody","site-specific-conjugation","t-cell-engager"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-translational-valley","b-ip-collaboration"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"An open ADC and bispecific platform enables at least ten academic first-in-human trials of conjugates against novel or rare-cancer antigens within five years, compared with near zero today, and at least two are subsequently licensed.","rationale":"Modern ADC success is largely payload and linker engineering, which is patent-encumbered and inaccessible to academics; the antigens most likely to matter for rare cancers are found in academia. Open tool infrastructure has repeatedly seeded new fields (SGC probes, Addgene plasmids).","test":"Fund the platform for three years, count academic conjugate programmes reaching GMP manufacturing and first-in-human dosing, and compare with the prior five-year baseline.","maturity":"speculative","actor":"engineering","cost":"medium","horizonYears":4},{"id":"idea-tr2-combination-forecast-tournament","kind":"idea","name":"An open forecasting tournament on which combination trials will succeed","aka":[],"tldr":"Ask experts and models to predict, in public, which registered combination trials will meet their endpoint. Track who is right, and use the best forecasters to decide what to fund.","summary":"Forecasting tournaments (Good Judgment Project, the replication-prediction markets in psychology) show that aggregated, scored predictions outperform committees. Applying this to registered oncology combination trials would create a calibrated prior for each combination, expose which mechanistic arguments actually predict success, and give funders a quantitative tool for prioritisation.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Too many combinations to test): Palmer & Sorger, Combination cancer therapy can confer benefit via patient-to-patient variability without drug additivity or synergy (Cell 2017)","url":"https://doi.org/10.1016/j.cell.2017.11.009"}],"tags":[],"related":["clinicaltrials-gov","idea-tr2-synergy-ranking-engine"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-combination-space","b-funding-allocation"],"keyPapers":["paper-palmer-cell"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Aggregated tournament forecasts will discriminate successful from failed combination trials with an area under the curve above 0.75, better than expert panels or sponsor stage-gates.","rationale":"Replication prediction markets forecast which psychology findings would replicate with roughly 70% accuracy. Trial outcomes are similarly forecastable from design, prior data and sponsor behaviour.","test":"Run a two-year tournament on 100 registered phase 2 and 3 combination trials with readouts due; score Brier and discrimination against outcomes.","maturity":"speculative","actor":"data","cost":"small","horizonYears":2},{"id":"idea-data-open-cell-foundation-model","kind":"idea","name":"An open foundation model of the cancer cell trained on perturbation data","aka":[],"tldr":"Build a shared, openly available AI model that has learned how cancer cells respond to genetic and drug perturbations, so any lab can predict what a new drug or combination might do.","summary":"Single-cell perturbation atlases, CRISPR screens (DepMap), drug-response datasets and proteomics now exist at scale, but models trained on them are mostly proprietary or single-lab. The proposal is a pre-competitive, openly licensed foundation model of the cancer cell (transcriptomic and proteomic state under perturbation) trained on pooled public and consortium data with open weights, evaluated on held-out perturbations and prospective wet-lab validation, in the way AlphaFold became shared infrastructure for structure. The Chan Zuckerberg Initiative's virtual cell work and the Arc Institute's efforts are precedents.","asOf":"2026-09-08","links":[{"label":"DepMap","url":"https://depmap.org/portal/"},{"label":"CZI virtual cell","url":"https://virtualcellmodels.cziscience.com/"}],"tags":[],"related":["depmap","cellxgene-hca"],"cancers":[],"sections":["ai-computation","drug-discovery"],"technologies":["crispr-screens","single-cell-spatial","ai-drug-design"],"targets":[],"drugs":[],"companies":[],"institutions":["broad-institute"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-ai-validation","b-preclinical-models","b-combination-space"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"An open cell model will predict the transcriptional response to unseen drug and gene perturbations in unseen cell lines with accuracy sufficient to prioritise combinations, and prospectively validated predictions will yield synergistic combinations at a rate several times higher than random screening.","rationale":"AlphaFold showed that a shared open model on curated public data can lift an entire field; perturbation biology now has the data volume and benchmark structure to attempt the same.","test":"Train on public perturbation data with a held-out set of drugs and cell lines; test the top 100 predicted synergistic combinations in wet-lab screens against 100 random combinations; report hit rates.","maturity":"preclinical-evidence","actor":"philanthropy","cost":"large","horizonYears":4},{"id":"idea-acc-open-oncology-workforce-model","kind":"idea","name":"An open global model of cancer workforce supply and demand by country","aka":[],"tldr":"No one knows exactly how many oncologists, nurses, physicists and pathologists each country has or needs. A public, regularly updated model would let governments plan training and spot shortfalls years ahead.","summary":"Estimates of oncology workforce density are scattered across surveys and often a decade old. An open model combining registry burden (GLOBOCAN), treatment utilisation rates, professional-body registers, and training-pipeline data would project supply and demand by profession and country to 2040 and would show the effect of training decisions. The model would be maintained as a public good with annual updates.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Not enough oncologists, nurses, pathologists, physicists): Yang et al., Projected supply of and demand for oncologists and radiation oncologists through 2025 (JOP 2014)","url":"https://doi.org/10.1200/JOP.2013.001319"}],"tags":[],"related":["globocan"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["iarc"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-workforce","b-data-silos"],"keyPapers":["paper-yang-j-oncol-pract"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Countries using the model to set training quotas will reduce the projected 2035 shortfall in at least two professions by more than 20% relative to business-as-usual, as measured by subsequent registration data.","rationale":"Health workforce planning models exist for nurses and physicians in general; oncology has the burden and utilisation data needed but has never assembled them.","test":"Build and publish the model; validate historical projections against current registers in ten countries; track policy uptake and quota changes.","maturity":"speculative","actor":"data","cost":"small","horizonYears":2},{"id":"idea-reg-closed-manufacturing-interop-standard","kind":"idea","name":"An open interoperability standard for closed automated cell-processing machines","aka":[],"tldr":"Each cell-therapy machine uses its own proprietary process and cartridges. A common standard would let a process run on any machine, like a document opening in any word processor.","summary":"Closed automated systems (Miltenyi CliniMACS Prodigy, Lonza Cocoon, Cellares Cell Shuttle, Ori Biotech and others) each lock a process to one platform, so a product validated on one cannot move without a full comparability exercise. The proposal is an open standard for process description (unit operations, parameters, in-process controls, data schema) and for consumable interfaces, maintained by a standards body with regulator participation, plus a shared comparability framework so that moving a validated process between compliant platforms requires a defined, reduced data package.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Manufacturing cost and time for living and radioactive medicines): Hernandez, Prasad & Gellad, Total costs of chimeric antigen receptor T-cell immunotherapy (JAMA Oncology 2018)","url":"https://doi.org/10.1001/jamaoncol.2018.0977"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["car-t","til-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-manufacturing-cell-therapy"],"keyPapers":["paper-hernandez-jama-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Products built to the standard can be transferred between compliant platforms with a comparability package a quarter the size of today's, and the number of manufacturing sites per approved cell therapy doubles within five years.","rationale":"Interoperability standards (DICOM in imaging, HL7 FHIR in records) unlocked competition and scale in adjacent fields. Vendor lock-in currently makes each cell-therapy process a single point of failure.","test":"Convene manufacturers, three device vendors and two regulators to publish version 1 of the standard, then demonstrate transfer of one CD19 CAR-T process between two compliant devices with side-by-side release data.","maturity":"speculative","actor":"engineering","cost":"medium","horizonYears":4},{"id":"idea-data-open-evidence-knowledge-graph","kind":"idea","name":"An open knowledge graph linking trials, results, biomarkers, drugs and recommendations","aka":[],"tldr":"Build a public, machine-readable map connecting every cancer trial to its results, the drugs and biomarkers involved, and the guideline recommendations it supports, with a source for every link.","summary":"Evidence in oncology is scattered across registries, papers, labels and guidelines with no shared identifiers. An open knowledge graph (trial identifiers, PICO elements, structured results, drug and biomarker ontologies, guideline recommendations, provenance for each edge) would let software answer 'what is the evidence for drug X in population Y' reproducibly. OncoKB, CIViC, Open Targets and ClinicalTrials.gov are partial graphs; the proposal funds their federation under open licences with a governance body and curation incentives.","asOf":"2026-09-08","links":[{"label":"Open Targets","url":"https://www.opentargets.org/"}],"tags":[],"related":["oncokb","civic","open-targets","clinicaltrials-gov","awesome-cancer-variant-resources"],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-knowledge-diffusion","b-data-silos"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"An open evidence graph will reduce the time to compile the evidence base for a guideline question from weeks of manual review to hours, and will be adopted as the backbone of at least three decision-support products within three years.","rationale":"Open Targets and Wikidata show that open, federated knowledge graphs with provenance attract community curation and become infrastructure; oncology's clinical evidence layer lacks one.","test":"Build the graph for two diseases from existing open sources; have guideline panels use it for one update cycle and measure time saved and errors found versus manual review.","maturity":"early-clinical","actor":"philanthropy","cost":"medium","horizonYears":3},{"id":"idea-data-rwe-rct-calibration-library","kind":"idea","name":"An open library pairing completed cancer trials with real-world emulations","aka":[],"tldr":"Build a public library in which every phase 3 cancer trial is paired with a real-world emulation in federated hospital data, publishing how far the two agree in direction, magnitude and confidence interval overlap. Oncology needs its own calibration set because RCT-DUPLICATE covered mostly cardiometabolic disease, and it would map which question types can be trusted.","summary":"RCT-DUPLICATE calibrated real-world methods against trials mostly in cardiometabolic disease; oncology, with its time-varying treatments and surrogate endpoints, needs its own calibration set. The proposal funds a standing programme that emulates every phase 3 oncology trial with a real-world counterpart in federated data, publishes agreement metrics (direction, magnitude, confidence interval overlap), and maintains a public map of which question types (first-line comparisons, sequencing, dose) are emulable.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Weak real-world evidence and registries): Gyawali, Hey & Kesselheim, Assessment of the clinical benefit of cancer drugs receiving accelerated approval (JAMA Intern Med 2019)","url":"https://doi.org/10.1001/jamainternmed.2019.0462"}],"tags":[],"related":["idea-data-target-trial-emulation-standard"],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["real-world-evidence"],"trials":[],"people":[],"bottlenecks":["b-real-world-evidence"],"keyPapers":["paper-gyawali-jama-intern-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Across 100 oncology trials, emulation agreement will be high for first-line drug-versus-drug comparisons with hard endpoints and poor for questions involving progression-based endpoints or treatment switching, giving regulators an evidence-based rule for when RWE can substitute for a trial.","rationale":"Without a calibration library, every RWE submission is argued case by case. A map of emulability converts the debate into a lookup table.","test":"Fund the first 30 emulations across breast, lung and prostate; publish agreement metrics; test whether the resulting rule predicts agreement in the next 20.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":3},{"id":"idea-bio1-covalent-ligandability-atlas","kind":"idea","name":"An open map of which cancer proteins any drug can stick to","aka":[],"tldr":"Most cancer proteins have never been tested to see whether a small molecule can attach to them at all. A public map of what is chemically reachable would tell the field where to aim.","summary":"Activity-based protein profiling with covalent fragment libraries can measure ligandable sites across thousands of proteins in cancer cell lysates and live cells. Existing datasets are partial and largely proprietary. A precompetitive atlas covering the cysteine, lysine and tyrosine proteomes across 50 cancer models, published openly with hit compounds deposited, would convert 'undruggable' from an assertion into a measurement.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The undruggable drivers): Dang et al., Drugging the 'undruggable' cancer targets (Nature Reviews Cancer 2017)","url":"https://doi.org/10.1038/nrc.2017.36"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["proteomics","ai-drug-design"],"targets":[],"drugs":[],"companies":["frontier-medicines"],"institutions":["broad-institute","icr-london"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-undruggable-targets","b-reproducibility"],"keyPapers":["paper-dang-nat-rev-cancer"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Systematic covalent fragment profiling identifies ligandable sites on at least 200 proteins currently classified as undruggable, and at least ten of these yield functional chemical probes within three years.","rationale":"The approach found the ligandable site that became the KRAS G12C drug class. Coverage, not concept, is the limiting factor, and the cost per protein falls sharply with shared infrastructure.","test":"Fund two chemoproteomics centres for three years with mandated quarterly public data release; count new ligandable sites and probes independently reproduced by a third laboratory.","maturity":"preclinical-evidence","actor":"philanthropy","cost":"medium","horizonYears":4},{"id":"idea-bio2-rare-tumour-model-bank","kind":"idea","name":"An open model bank for the rare tumours nobody has models for","aka":[],"tldr":"You cannot study a cancer without a laboratory model of it, and most rare cancers have none. A funded bank that makes and shares models would unlock research.","summary":"Rare tumour research stalls because there is no cell line, organoid or xenograft to work with, and individual laboratories cannot justify the cost of derivation for a disease they may study once. A central derivation facility taking fresh surgical material from a referral network, generating organoids and xenografts, characterising them and distributing them openly on a cost-recovery basis would remove the barrier for hundreds of diseases at once.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Rare and paediatric cancers without markets): Gatta et al., Rare cancers are not so rare: the rare cancer burden in Europe (EJC 2011)","url":"https://doi.org/10.1016/j.ejca.2011.08.008"}],"tags":[],"related":["cancer-models","depmap"],"cancers":["sarcoma","neuroendocrine","cholangiocarcinoma","mesothelioma"],"sections":[],"technologies":["organoids","pdx-models","functional-drug-testing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-rare-cancers","b-preclinical-models","b-translational-valley"],"keyPapers":["paper-gatta-eur-j-cancer"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A central facility can derive usable models for at least half of attempted rare tumour cases and distribute over 200 characterised models within five years, measurably increasing publications and drug programmes in those diseases.","rationale":"Shared model repositories have driven whole fields, and dependency map projects showed that model availability, not ideas, determines what gets studied. Rare tumour surgery already generates the tissue, which is currently discarded.","test":"A two-year pilot with three referral centres reporting derivation success rate by histology, cost per model, and external requests served.","maturity":"preclinical-evidence","actor":"philanthropy","cost":"medium","horizonYears":6},{"id":"idea-moon-open-cancer-cell-state-model","kind":"idea","name":"An open model of every cancer cell state, built from perturbation atlases","aka":[],"tldr":"Map every state a cancer cell can be in, and how drugs and the surrounding tissue move it between states, into an open computational model anyone can query and improve.","summary":"Single-cell and spatial atlases (Human Tumor Atlas Network, Human Cell Atlas) describe cell states; perturbation screens and foundation models trained on them begin to predict responses. The proposal is a coordinated, openly licensed effort to generate perturbation-response single-cell data across hundreds of models and patient samples, train and release a foundation model of cancer cell state transitions, and benchmark it prospectively against drug response in organoids and trials, with the data, weights and benchmarks all public.","asOf":"2026-09-08","links":[{"label":"Human Tumor Atlas Network","url":"https://humantumoratlas.org/"},{"label":"Human Cell Atlas","url":"https://www.humancellatlas.org/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["single-cell-spatial","crispr-screens","organoids","pathology-foundation-model"],"targets":[],"drugs":[],"companies":["10x-genomics"],"institutions":["broad-institute"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-tumor-heterogeneity","b-preclinical-models","b-reproducibility"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"An open cell-state model predicts drug response and resistance transitions in held-out patient samples better than existing biomarkers and shortens target and combination discovery cycles measurably.","rationale":"Heterogeneity and plasticity defeat single-marker approaches; only a model of states and transitions captures them. Open weights and benchmarks avoid the reproducibility failures of closed models.","test":"Release version one with prospective benchmark on organoid response; then a biomarker-defined trial in which model-predicted responders are enriched and outcomes compared with standard selection.","maturity":"preclinical-evidence","actor":"research","cost":"large","horizonYears":6},{"id":"idea-bio1-rare-cancer-organoid-bank","kind":"idea","name":"An open organoid bank for cancers too rare to have models","aka":[],"tldr":"Rare and paediatric cancers often have no cell line or xenograft anywhere in the world, so no one can test drugs on them. A funded network collecting tissue at referral centres, deriving organoids under one protocol and distributing them at cost with no reach-through rights would change that.","summary":"Rare and paediatric cancers lack cell lines and xenografts, which blocks even basic drug testing. A distributed programme would fund collection at referral centres, derive organoids and xenografts under a common protocol, characterise them genomically, and distribute them at cost with no reach-through rights. Precedents include the Human Cancer Models Initiative and paediatric preclinical testing programmes.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Lab models that fail to predict what happens in patients): Wong, Siah & Lo, Estimation of clinical trial success rates (Biostatistics 2019)","url":"https://doi.org/10.1093/biostatistics/kxx069"}],"tags":[],"related":[],"cancers":["sarcoma","neuroblastoma","cholangiocarcinoma"],"sections":[],"technologies":["organoids","pdx-models"],"targets":[],"drugs":[],"companies":[],"institutions":["nci","cold-spring-harbor"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-preclinical-models","b-rare-cancers"],"keyPapers":["paper-wong-biostatistics"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Providing at least three characterised models for each of 50 rare cancer types measurably increases the number of published drug-testing studies and industry programmes in those diseases within five years.","rationale":"Model scarcity, not biological intractability, is the first barrier for rare disease drug development; a model is a prerequisite for any preclinical package.","test":"Fund derivation for ten rare types, distribute openly, and count downstream requests, publications and programme starts against matched types without models.","maturity":"preclinical-evidence","actor":"philanthropy","cost":"medium","horizonYears":5},{"id":"idea-moon-supplement-interaction-database","kind":"idea","name":"An open supplement-drug interaction checker built into oncology prescribing","aka":[],"tldr":"Most patients take supplements and rarely tell their oncologist. Ask routinely and check automatically for interactions with chemotherapy and targeted drugs.","summary":"Herbal and dietary supplement use is common in cancer patients and can alter drug metabolism (St John's wort, curcumin, green tea extract with certain kinase inhibitors) or interfere with treatment. Data are scattered across MSK's About Herbs, pharmacology references and case reports. The proposal is a curated open database of supplement-anticancer drug interactions with evidence grades, integrated into electronic prescribing so that documented supplement use triggers an alert, plus a standard intake question at every prescribing visit.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Misinformation and unproven therapies): Johnson et al., Cancer misinformation and harmful information on Facebook and other social media (JNCI 2022)","url":"https://doi.org/10.1093/jnci/djab141"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["mskcc"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-misinformation","b-toxicity-qol"],"keyPapers":["paper-johnson-j-natl-cancer-inst"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Routine intake and automated checking increase documented supplement use severalfold and reduce clinically relevant interactions and unexplained toxicity or subtherapeutic exposure.","rationale":"Disclosure rises when asked non-judgementally; interaction knowledge exists but is not at the point of care.","test":"Implement in two centres; measure documentation rates, alert frequency and pharmacist-confirmed interactions before and after.","maturity":"early-clinical","actor":"data","cost":"small","horizonYears":2},{"id":"idea-acc-open-hardware-linac","kind":"idea","name":"An open-hardware radiotherapy machine built for unreliable power and dust","aka":[],"tldr":"Design a radiotherapy machine from scratch for hospitals with patchy electricity, heat and few engineers, and publish the design so several companies can build it cheaply.","summary":"Commercial linear accelerators are built for well-staffed Western hospitals; in sub-Saharan Africa they sit idle for long stretches because of power failures, heat, and the cost of a service call. A consortium (the CERN/STFC/ICEC 'Project STELLA' work is a precedent) would specify a ruggedised, modular, remotely diagnosable machine with battery-buffered power, sealed electronics, swappable modules that a local technician can replace, and an open interface specification. The design and test data would be published so multiple manufacturers can bid; the buyer pays for uptime, not for the box.","asOf":"2026-09-08","links":[{"label":"IAEA DIRAC directory of radiotherapy centres","url":"https://dirac.iaea.org/"},{"label":"IAEA Rays of Hope","url":"https://www.iaea.org/services/rays-of-hope"}],"tags":[],"related":[],"cancers":[],"sections":["radiation"],"technologies":["imrt-igrt"],"targets":[],"drugs":[],"companies":["varian","elekta","united-imaging"],"institutions":["iarc"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-global-access","b-surgery-radiation-innovation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A purpose-designed machine will achieve more than 90% scheduled uptime in district hospitals in sub-Saharan Africa, against a historical figure well below that for conventional linacs in the same settings, at a total ten-year cost of ownership at least 40% lower.","rationale":"Every other capital good used in low-resource health systems (solar vaccine refrigerators, oxygen concentrators, GeneXpert) was eventually redesigned for the environment rather than shipped as-is. Radiotherapy has never had that redesign, despite the IAEA DIRAC database showing dozens of countries with one or zero working machines.","test":"Fund a two-year design phase with a published requirements document, then a three-site field trial (one machine each in three countries) measuring uptime, mean time to repair, dose accuracy audits by the IAEA, and patients treated per month against a matched conventional linac.","maturity":"speculative","actor":"engineering","cost":"large","horizonYears":7},{"id":"idea-fund-precompetitive-undruggable-consortium","kind":"idea","name":"An open-science consortium on the undruggable drivers, open until a candidate","aka":[],"tldr":"Companies and public funders would pool money and scientists to crack the hardest cancer proteins, such as MYC and mutant p53, sharing everything openly until there is a real drug candidate, then competing on the final product.","summary":"A consortium on the Structural Genomics Consortium and Open Targets model, but aimed at the highest-value undruggable oncology targets: MYC, mutant p53 reactivation, non-G12C RAS alleles beyond current inhibitors, fusion oncoproteins, transcription-factor and phosphatase targets. Members fund shared structural biology, chemical biology, degrader and molecular glue platforms and open probe generation, with an agreement that all results are published without patents up to the point of a validated chemical series, after which members may file and compete. The public benefit is a decade of duplicated, secret failure replaced by a shared map of what does and does not work.","asOf":"2026-09-08","links":[{"label":"Structural Genomics Consortium","url":"https://www.thesgc.org/"},{"label":"Open Targets","url":"https://www.opentargets.org/"}],"tags":[],"related":["idea-fund-first-in-class-prize","idea-fund-target-validation-consortium","kras-roadmap"],"cancers":[],"sections":[],"technologies":["protac-degrader","ai-drug-design"],"targets":["tp53","kras","menin"],"drugs":[],"companies":[],"institutions":["broad-institute","francis-crick"],"pathways":["p53-cell-cycle","ras-mapk"],"terms":[],"trials":[],"people":[],"bottlenecks":["b-ip-collaboration","b-undruggable-targets"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"An open consortium of at least eight companies and three public funders produces open, potent chemical probes for at least three previously undrugged oncology target classes within six years and at least two members enter clinical development with compounds derived from consortium-enabled chemistry.","rationale":"SGC has released hundreds of structures and dozens of open chemical probes that seeded later drug programmes (including in epigenetics), demonstrating that competitors will share pre-competitive science; KRAS G12C became druggable through academic chemistry that was widely published, after which competition produced multiple drugs quickly.","test":"Constitute the consortium with a three-target initial portfolio and publish annual progress including negative results; success at year four is at least one open probe with demonstrated cellular activity per target class.","maturity":"early-clinical","actor":"industry","cost":"large","horizonYears":6},{"id":"idea-bio2-organotropism-atlas","kind":"idea","name":"An organotropism atlas that predicts where a cancer will spread","aka":[],"tldr":"Different cancers favour different organs, and so do different patients. A model that predicts which organ is at risk could target surveillance and prevention.","summary":"Site of relapse is recorded in registries and trial datasets but almost never modelled as an outcome. Linking primary tumour genomics, transcriptomics and digital pathology to first-relapse site across tens of thousands of patients would produce an organotropism predictor, and would identify the features that drive lung, liver, bone and brain tropism in humans rather than in mice.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Metastasis is understood least and studied last): Dillekås et al., Are 90% of deaths from cancer caused by metastases? (Cancer Medicine 2019)","url":"https://doi.org/10.1002/cam4.2474"}],"tags":[],"related":["genie","seer","cbioportal"],"cancers":["breast-her2-positive","melanoma","prostate"],"sections":[],"technologies":["pathology-foundation-model","rna-seq"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-metastasis-biology","b-data-silos","b-real-world-evidence"],"keyPapers":["paper-dillekas-cancer-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A multimodal model trained on primary tumour features predicts first metastatic site with an AUC above 0.7 in held-out cohorts, and its top features nominate druggable organ-specific seeding mechanisms.","rationale":"Human organotropism is strikingly reproducible by subtype (HER2-positive breast to brain, luminal breast to bone, uveal melanoma to liver) but has never been systematically explained. Existing registry and trial data can answer it without collecting new samples.","test":"Federated analysis across three national registries plus genomics-linked outcome data; publish the model, then validate it prospectively by predicting relapse site in an ongoing adjuvant cohort.","maturity":"speculative","actor":"data","cost":"medium","horizonYears":6},{"id":"idea-tr1-sex-stratified-pk-and-dosing","kind":"idea","name":"Analyse and dose by sex: women get more toxicity from many cancer drugs at the same dose","aka":[],"tldr":"Women get more severe side effects than men at identical doses of fluorouracil, several kinase inhibitors and immune checkpoint inhibitors in pooled analyses. Trials should pre-specify sex-stratified drug level and toxicity analyses and, where they differ, run sex-specific dose-finding and label accordingly.","summary":"Registrational trials pre-specify sex-stratified PK, exposure-response and toxicity analyses; where exposure or toxicity differs, dose-finding includes sex-specific cohorts and labels carry sex-specific guidance. Fluorouracil, several TKIs and immune checkpoint inhibitors show sex differences in toxicity in pooled analyses; the mechanism (body composition, clearance, immune biology) varies by drug.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Trials do not represent the people who get cancer): Loree et al., Disparity of race reporting and representation in trials leading to cancer drug approvals (JAMA Oncology 2019)","url":"https://doi.org/10.1001/jamaoncol.2019.1870"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["cytotoxic-chemotherapy","kinase-inhibitors"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-diversity","b-dose-optimisation","b-toxicity-qol"],"keyPapers":["paper-loree-jama-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Sex-stratified analysis will reveal clinically relevant exposure differences for a meaningful fraction of agents, and sex-adjusted dosing will reduce grade 3+ toxicity in women without reducing efficacy.","rationale":"Sex is the most basic stratifier and is routinely ignored in dose selection; pharmacology differences by sex are documented and body-surface-area dosing does not remove them.","test":"Pooled re-analysis of existing trial datasets by sex for toxicity and exposure; then a randomised sex-adjusted dosing study of one agent with a documented difference.","maturity":"early-clinical","actor":"industry","cost":"small","horizonYears":3},{"id":"idea-tr1-ancestry-aware-pharmacology-programme","kind":"idea","name":"Ancestry-aware pharmacology: drug-level sub-studies across populations before approval","aka":[],"tldr":"Drugs are processed differently by people with different genetic backgrounds, but doses are set mostly in white and East Asian populations. Every new drug should be studied for how it behaves across ancestries, with dosing advice by genotype rather than by race.","summary":"Registrational programmes include pharmacokinetic and pharmacogenomic sub-studies powered across the main genetic ancestry groups, genotyping known variants (CYP2D6, CYP3A5, UGT1A1, DPYD, NUDT15, HLA alleles) and reporting exposure and toxicity by genotype. Labels carry genotype-based dosing where exposure differs, replacing crude race-based statements. African, South Asian and Indigenous populations are prioritised because they are least represented in existing PK data.","asOf":"2026-09-08","links":[{"label":"CPIC guideline: fluoropyrimidines and DPYD","url":"https://cpicpgx.org/guidelines/guideline-for-fluoropyrimidines-and-dpyd/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["germline-testing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["germline-vs-somatic"],"trials":[],"people":[],"bottlenecks":["b-trial-diversity","b-dose-optimisation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Ancestry-aware programmes will identify clinically relevant exposure differences for a meaningful fraction of new oral oncology agents, and genotype-guided dosing will reduce grade 3+ toxicity in affected groups without loss of efficacy.","rationale":"Known examples include NUDT15 variants and thiopurine toxicity in East Asian and Hispanic patients, UGT1A1*28 and irinotecan, and DPYD variants and fluoropyrimidines; several were discovered only after approval and harm.","test":"Mandate the sub-study for new oral agents for three years and count label changes attributable to it; run a genotype-guided dosing RCT for one agent with a discovered difference.","maturity":"early-clinical","actor":"regulator","cost":"medium","horizonYears":4},{"id":"idea-bio2-tumour-anchored-tgfbeta-trap","kind":"idea","name":"Anchor a TGF-beta trap in the tumour stroma so it cannot act everywhere","aka":[],"tldr":"TGF-beta is a signal that keeps immune cells out of tumours, but blocking it throughout the body caused bleeding and heart toxicity and sank bintrafusp alfa. Tethering the blocker to tumour stroma with a FAP anchor, a collagen-binding domain or a protease-activated mask could give the benefit without the harm.","summary":"Systemic TGF-beta blockade, including the PD-L1-TGF-beta trap bintrafusp alfa, failed largely on a narrow therapeutic index with bleeding and cardiac toxicity. Localisation strategies (a FAP-anchored trap, a collagen-binding domain fusion, or a protease-activated masked format) restrict activity to stroma-rich tumour tissue, and masked antibody formats are already in clinical trials.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Cold tumours and the immunosuppressive microenvironment): Haslam & Prasad, Estimation of the percentage of US patients eligible for and responding to checkpoint inhibitors (JAMA Netw Open 2019)","url":"https://doi.org/10.1001/jamanetworkopen.2019.2535"}],"tags":[],"related":[],"cancers":["urothelial","pancreatic"],"sections":[],"technologies":["masked-adc","bispecific-antibody","checkpoint-inhibitor"],"targets":["fap","pdl1"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["desmoplasia","cold-vs-hot"],"trials":[],"people":[],"bottlenecks":["b-tme-immunosuppression","b-toxicity-qol"],"keyPapers":["paper-haslam-jama-netw-open","paper-pd-l1-urothelial-mol-cancer-ther-2015","paper-pd-l1-urothelial-trends-mol-med-2015","paper-pd-l1-urothelial-onco-targets-ther-2016"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A stroma-anchored TGF-beta trap achieves at least tenfold higher tumour-to-plasma target engagement than an unanchored trap and increases T-cell penetration into the tumour core without cardiovascular toxicity.","rationale":"TGF-beta is one of the best-validated barriers to T-cell infiltration in human tumours, notably in urothelial cancer where a stromal TGF-beta signature predicts checkpoint failure. The failure of systemic agents is an index problem, and localisation is the standard fix.","test":"Preclinical head-to-head of anchored versus systemic trap for exposure ratio and toxicity, then a phase 1 with paired biopsies measuring stromal phospho-SMAD2 suppression and CD8 distribution relative to stroma.","maturity":"preclinical-evidence","actor":"industry","cost":"medium","horizonYears":7},{"id":"idea-cost-real-time-pa-fhir","kind":"idea","name":"Answer prior authorisation requests in seconds from the medical record","aka":[],"tldr":"Most cancer drug approvals depend on a handful of facts already in the chart, such as the diagnosis, biomarker and line of therapy; sending those automatically in a standard format would return most decisions before the patient leaves the room.","summary":"CMS's 2024 Interoperability and Prior Authorization final rule requires payers to offer electronic prior authorisation through HL7 FHIR interfaces and to decide urgent requests within 72 hours and standard ones within seven days from 2026 and 2027. Oncology criteria are structured (diagnosis, stage, biomarker, prior lines), so the mCODE data standard can carry them. Payers publishing their oncology rules as computable criteria, and electronic records sending mCODE bundles, turns a fax-and-phone process into an automated one with human review only for exceptions.","asOf":"2026-09-10","links":[{"label":"CMS Interoperability and Prior Authorization final rule (CMS-0057-F, January 2024)","url":"https://www.cms.gov/priorities/key-initiatives/burden-reduction/interoperability/policies-and-regulations/cms-interoperability-and-prior-authorization-final-rule-cms-0057-f"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["hl7"],"pathways":[],"terms":["mcode","nccn-compendium"],"trials":[],"people":[],"bottlenecks":["b-care-fragmentation","b-data-silos","b-workforce"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Automated FHIR-based oncology prior authorisation will decide more than 70% of requests within one hour and cut practice administrative cost per request by more than half.","rationale":"The regulatory deadlines are set; the data standards exist; the remaining work is mapping each payer's criteria into computable rules.","test":"Payer and practice pilots reporting decision times, share auto-approved, appeal rates and staff hours before and after.","maturity":"being-tested-at-scale","actor":"data","cost":"medium","horizonYears":2},{"id":"idea-prev-hpylori-stool-resistance-guided","kind":"idea","name":"Antibiotic-resistance testing from a stool sample before treating H. pylori","aka":[],"tldr":"H. pylori eradication often fails because of antibiotic resistance. A stool DNA test showing which antibiotics will work would raise cure rates and protect antibiotics.","summary":"Helicobacter pylori eradication often fails because of antibiotic resistance, so this idea runs a stool PCR for 23S rRNA and gyrA resistance mutations before treatment and tailors first-line therapy accordingly in mass eradication programmes. Clarithromycin resistance is now common in many regions, tailored-therapy RCTs already show superiority over empirical treatment, and stool testing removes the need for endoscopy. Endpoints are eradication rate and antibiotic consumption, with the aim of higher cure rates and less macrolide use, protecting antibiotics as well as preventing gastric cancer. The test is an RCT of 5,000 patients within a population programme. At early-clinical maturity it addresses the bottleneck Prevention we already have is not deployed.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Prevention we already have is not deployed): Islami et al., Proportion of cancer attributable to modifiable risk factors (CA 2018)","url":"https://doi.org/10.3322/caac.21440"}],"tags":[],"related":[],"cancers":["gastric"],"sections":["prevention"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption"],"keyPapers":["paper-islami-ca-cancer-j-clin"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Resistance-guided therapy achieves at least 90% eradication versus about 75% for empirical therapy and reduces macrolide use by at least 40%.","rationale":"Tailored-therapy RCTs already show superiority; stool PCR removes the need for endoscopy.","test":"Run an RCT of 5,000 patients within a population programme.","maturity":"early-clinical","actor":"clinic","cost":"medium","horizonYears":3},{"id":"idea-bio1-pmhc-bispecifics-public-drivers","kind":"idea","name":"Antibodies that see mutant KRAS and p53 fragments displayed on the cell surface","aka":[],"tldr":"Cells chop up their internal proteins and display the pieces on their surface. That means even undruggable proteins inside the cell can be attacked from outside by the immune system.","summary":"TCR-mimic antibodies and bispecific T-cell engagers can recognise mutant peptide-MHC complexes, including KRAS G12V and TP53 R175H presented on HLA-A*02:01, with published proof of concept. Tebentafusp validated the ImmTAC format clinically in uveal melanoma. The proposal is a coordinated programme covering the commonest driver mutations across the commonest HLA alleles, treating public neoantigens as an off-the-shelf target class.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The undruggable drivers): Dang et al., Drugging the 'undruggable' cancer targets (Nature Reviews Cancer 2017)","url":"https://doi.org/10.1038/nrc.2017.36"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["t-cell-engager","bispecific-antibody","tcr-t"],"targets":["kras","tp53"],"drugs":["tebentafusp"],"companies":["immunocore","immatics","tscan"],"institutions":[],"pathways":[],"terms":["neoantigen"],"trials":[],"people":[],"bottlenecks":["b-undruggable-targets","b-immunotherapy-response"],"keyPapers":["paper-vogelstein-surfing-p53-network-nature-2000","paper-dang-nat-rev-cancer"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A pMHC-directed bispecific against a public driver neoantigen produces objective responses in HLA-matched, mutation-positive patients, demonstrating that intracellular undruggable drivers are immunologically targetable.","rationale":"The approach makes druggability a question of antigen presentation rather than protein pockets, and the driver mutations are truncal, so escape by antigen loss requires losing the driver itself.","test":"First-in-human study in HLA-A*02:01-positive, KRAS G12V-positive pancreatic or colorectal cancer, with mandatory HLA and mutation screening and on-treatment biopsies for T-cell infiltration.","maturity":"preclinical-evidence","actor":"industry","cost":"large","horizonYears":6},{"id":"idea-adc-for-mesothelioma","kind":"idea","name":"Antibody-drug conjugates for mesothelioma: why they have failed so far and how they could work","aka":[],"tldr":"Nearly every mesothelioma carries the surface protein mesothelin, yet the one antibody-drug conjugate tried in a randomised trial did no better than chemotherapy. The idea is to fix the three reasons it failed rather than abandon the approach.","summary":"Mesothelioma looks ideal for antibody-drug conjugates: mesothelin is on almost every tumour cell and rare elsewhere. Anetumab ravtansine, a mesothelin antibody carrying the tubulin poison DM4, proved otherwise in 248 patients, matching vinorelbine's 4.5-month progression-free survival and no more. Three explanations have evidence behind them. Mesothelioma sheds soluble mesothelin into the blood, which binds the antibody before it reaches the tumour. Expression is patchy and the tumour grows as thin sheets with dense stroma, so few cells take up enough payload. And a tubulin payload adds little to a slow-cycling tumour that already resists chemotherapy. The idea proposes conjugates built for these facts: antibodies that bind membrane mesothelin epitopes not present on the shed form, topoisomerase I payloads with a bystander effect that kill neighbouring cells that took up no drug (the DXd and SN-38 class that transformed breast and lung cancer ADCs), regional intrapleural delivery to bypass shed antigen in blood, and combination with PD-1 blockade to turn payload-induced cell death into an immune response, which the National Cancer Institute is already testing with anetumab ravtansine and pembrolizumab. Other targets present on mesothelioma, such as folate receptor alpha, on which the conjugate Rina-S is being tested across solid tumours, and B7-H3, widen the options beyond mesothelin.","asOf":"2026-09-07","links":[{"label":"Kindler et al., anetumab ravtansine versus vinorelbine (Lancet Oncology 2022)","url":"https://doi.org/10.1016/S1470-2045(22)00061-4"},{"label":"Pembrolizumab with or without anetumab ravtansine, NCT03126630","url":"https://clinicaltrials.gov/study/NCT03126630"},{"label":"Rinatabart sesutecan in advanced solid tumours, NCT05579366","url":"https://clinicaltrials.gov/study/NCT05579366"}],"tags":[],"related":[],"cancers":["mesothelioma"],"sections":[],"technologies":["adc","checkpoint-inhibitor"],"targets":["mesothelin"],"drugs":["anetumab-ravtansine","trastuzumab-deruxtecan"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["anetumab-vs-vinorelbine-mpm","nci-anetumab-pembrolizumab-mpm"],"people":[],"bottlenecks":[],"keyPapers":["paper-kindler-lancet-oncol","paper-mesothelin-mesothelioma-cancer-discov-2016","paper-mesothelin-mesothelioma-clin-cancer-res-2004","paper-mesothelin-mesothelioma-j-clin-oncol-2016"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A mesothelin- or FRα-directed conjugate with a bystander-capable topoisomerase I payload, given with PD-1 blockade, will produce a response rate above 30 percent and median progression-free survival beyond 8 months in second-line pleural mesothelioma, roughly double what vinorelbine or anetumab ravtansine achieved.","rationale":"Mesothelin expression is near universal in epithelioid mesothelioma; TOP1-payload ADCs with bystander killing succeeded where tubulin-payload ADCs failed in HER2-low breast cancer and in lung cancer; shed antigen and heterogeneity are documented and addressable; the pleural space is accessible for regional dosing.","test":"Expansion cohorts for mesothelioma in ongoing trials of TOP1-payload conjugates against mesothelin and folate receptor alpha, measuring soluble mesothelin as a stratification factor; then a randomised second-line trial against vinorelbine or gemcitabine with progression-free survival as the primary endpoint.","maturity":"early-clinical","actor":"industry","cost":"large","horizonYears":6},{"id":"idea-cost-optimus-legacy-drugs","kind":"idea","name":"Apply Project Optimus to drugs already on the market","aka":[],"tldr":"The FDA now requires new cancer drugs to prove their dose is the right one rather than the highest tolerated; asking the same question of the twenty best-selling approved drugs could cut doses, side effects and cost at once.","summary":"The FDA's Project Optimus and its 2024 final guidance require sponsors to compare doses before approval. Most approved targeted drugs and antibodies were never dose-optimised: a maximum tolerated dose from phase 1 became the label. A post-marketing programme, with FDA authority to require dose-comparison studies as a condition of continued approval or through the accelerated-approval confirmatory pathway, would revisit the doses of high-spend drugs. Lower or less frequent doses save money directly and reduce dose reductions and discontinuations that waste drug.","asOf":"2026-09-10","links":[{"label":"FDA guidance: Optimizing the Dosage of Human Prescription Drugs and Biological Products for the Treatment of Oncologic Diseases (August 2024)","url":"https://www.fda.gov/regulatory-information/search-fda-guidance-documents/optimizing-dosage-human-prescription-drugs-and-biological-products-treatment-oncologic-diseases"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["fda-oce","nci"],"pathways":[],"terms":["project-optimus"],"trials":[],"people":[],"bottlenecks":["b-dose-optimisation","b-drug-pricing","b-toxicity-qol"],"keyPapers":["paper-drug-dosing-conundrum-nejm-2021"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Post-marketing dose-optimisation studies of ten high-spend oncology drugs will find at least half can be given at a lower dose or longer interval with equal efficacy, saving more than 20% of spend on those drugs.","rationale":"Every time it has been tested (abiraterone, extended-interval pembrolizumab, six-month trastuzumab) a lower or shorter regimen has held up.","test":"FDA and NCI co-sponsor randomised dose-comparison trials embedded in cooperative groups, with efficacy, toxicity and cost endpoints.","maturity":"speculative","actor":"regulator","cost":"medium","horizonYears":4},{"id":"idea-reg-biosimilar-no-efficacy-trial","kind":"idea","name":"Approve cancer biosimilars on analytics and pharmacokinetics, no efficacy trials","aka":[],"tldr":"Copies of biological cancer drugs are still required to run large trials that rarely change the answer. Dropping them would cut years and tens of millions from each biosimilar.","summary":"The MHRA has not required comparative efficacy trials for most biosimilars since 2021, the EMA published a 2025 reflection paper proposing to waive them where analytical and pharmacokinetic similarity are shown, and FDA has signalled the same direction. Comparative efficacy trials for oncology monoclonal antibodies (trastuzumab, bevacizumab, rituximab, and soon pembrolizumab and nivolumab as patents expire around 2028) cost tens of millions and have essentially never overturned a positive analytical package. The proposal is a coordinated ICH-level waiver with a shared analytical similarity standard, so a biosimilar programme runs once for all regions.","asOf":"2026-09-08","links":[{"label":"EMA reflection paper on biosimilar clinical requirements","url":"https://www.ema.europa.eu/en/human-regulatory-overview/research-development/scientific-guidelines/multidisciplinary-guidelines/multidisciplinary-biosimilar"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["monoclonal-antibody"],"targets":[],"drugs":["trastuzumab","pembrolizumab","nivolumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-drug-pricing","b-regulatory-fragmentation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Waiving comparative efficacy trials reduces biosimilar development cost by at least $30 million and time by two years per product, doubling the number of biosimilar entrants for the first checkpoint inhibitor patent expiries, with no efficacy or immunogenicity signal in post-marketing surveillance.","rationale":"Analytical methods now characterise antibodies far more sensitively than clinical endpoints can, and the accumulated experience of dozens of approved biosimilars shows clinical efficacy trials add cost without discriminating power.","test":"Track the number of entrants, development timelines and post-marketing safety for biosimilars approved under the MHRA and EMA waivers against those approved with efficacy trials; harmonise the standard through ICH.","maturity":"being-tested-at-scale","actor":"regulator","cost":"small","horizonYears":3},{"id":"idea-nl-ask-about-diet-prebunking","kind":"idea","name":"Ask about diet at diagnosis, and prebunk the myths before the internet does","aka":[],"tldr":"Almost every newly diagnosed patient searches for what to eat and finds sugar-starvation, alkaline and juice-cure claims. If the oncology team asks about diet first and hands over good information, the myths have less room.","summary":"Patients report that clinicians rarely discuss diet, so they turn to social media and supplement marketing, where unproven claims dominate. Prebunking, warning people about a specific manipulation before they encounter it, has randomised evidence from misinformation research and from HPV vaccination. A short, structured diet and supplement conversation at the first oncology visit, with a dietitian-authored handout that names and explains the common myths and offers what is actually supported (fibre, protein, activity, alcohol, smoking), could be tested cheaply.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Misinformation and unproven therapies): Johnson et al., Cancer misinformation and harmful information on Facebook and other social media (JNCI 2022)","url":"https://doi.org/10.1093/jnci/djab141"}],"tags":[],"related":["idea-moon-prebunking-at-diagnosis","idea-moon-misinformation-rapid-response"],"cancers":[],"sections":["nutrition-lifestyle","supportive-care"],"technologies":["nutrition-screening-mnt","dietary-supplements-treatment-interactions","ketogenic-diet-glioblastoma"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["unproven-diet-claims","warburg-effect-diet-claims"],"trials":[],"people":[],"bottlenecks":["b-misinformation","b-patient-voice","b-knowledge-diffusion"],"keyPapers":["paper-johnson-j-natl-cancer-inst"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A five-minute structured diet conversation plus prebunking materials at the first oncology consultation reduces adoption of unproven diets and antioxidant supplements at three months by half and increases dietitian referral uptake, without increasing anxiety.","rationale":"Misinformation fills a vacuum; the evidence that patients want diet advice and do not get it is consistent; prebunking is cheap and has experimental support. Dietitian referral is the constructive alternative.","test":"Cluster-randomised trial across oncology clinics with patient-reported diet and supplement behaviours at 3 and 6 months, belief in specific myths, anxiety and dietitian referral rates as endpoints.","maturity":"speculative","actor":"clinic","cost":"small","horizonYears":2},{"id":"idea-rejuv-registry-randomised-screening-in-survivors","kind":"idea","name":"Ask whether survivorship screening saves lives, using registry-based randomisation","aka":[],"tldr":"No randomised trial has shown that screening survivors for a second cancer reduces death from it. A registry-based randomised trial, which invites rather than enrols, is the only design that could answer this at an affordable cost.","summary":"Survivors of chest radiotherapy given young are offered breast surveillance in the United Kingdom on the strength of their measured risk. Survivors of the same treatment are offered nothing for lung, skin, bowel or bladder, despite measured excess risks, and the reason is not that anyone decided against it. A conventional trial here is impossible: the latency is decades, each survivor group is small, and consenting people to no surveillance when their risk is known is not acceptable.\n\nA registry-based randomised design, as used in cardiology and in screening research, changes the economics. Eligible survivors are identified from a registry linkage, randomised to be invited or not invited to a surveillance pathway, and followed through the same registry for cancer incidence, stage at diagnosis and death. Nobody is denied care they would otherwise have had, because the comparator is the current default of no programme. The marginal cost is the invitation and the pathway, not a trial infrastructure.\n\nThe honest limits are that this answers the invitation question rather than the test question, that contamination from private screening would dilute the effect, and that mortality from a specific second cancer needs very large numbers or very long follow-up. Stage shift and interval cancers are the realistic interim endpoints.","asOf":"2026-10-02","links":[{"label":"ClinicalTrials.gov NCT06113016","url":"https://clinicaltrials.gov/study/NCT06113016"},{"label":"NHS England: very high risk breast screening protocol","url":"https://www.gov.uk/government/publications/breast-screening-very-high-risk-women-surveillance-protocols"}],"tags":["rejuvenation","survivorship","open-problem","screening"],"related":["rejuv-second-screening-after-treatment-compared","second-primary-lung-after-chest-radiotherapy","rejuv-second-uk-very-high-risk-breast-screening","idea-acc-tailored-second-cancer-screening","rejuvenation-roadmap"],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["rejuv-agenda-screening-without-a-trial","rejuv-agenda-late-effects-are-not-counted","b-survivorship","b-early-detection"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Inviting a defined survivor group with a measured excess risk to an organised surveillance pathway reduces death from that cancer, or at minimum shifts stage at diagnosis, compared with the current default of no programme.","rationale":"Measured excess risks in several survivor groups exceed the risk in populations for whom screening has been shown to save lives: second-primary lung cancer rates in survivors of some head and neck cancers exceed the rate in the control arm of the trial that established lung screening works. No country screens on the basis of treatment history. The only existing survivor programme, the United Kingdom's very high risk breast protocol, rests on inference rather than trial evidence, and that inference has never been tested in any organ.","test":"A registry-based randomised invitation trial in a country with linked cancer registry and treatment data: identify survivors meeting an exposure threshold, randomise to invitation or no invitation, and follow through the registry for incidence, stage distribution and cause-specific mortality. Start with lung after chest radiotherapy or thoracic treatment, where the comparator trial evidence in a non-survivor population already exists and the risk is highest.","maturity":"speculative","actor":"research","cost":"medium","horizonYears":10},{"id":"lymphoma-ev-genetic-subtype-directed-first-line","kind":"idea","name":"Assign first-line treatment in diffuse large B-cell lymphoma by genetic subtype, not by a three-antibody stain","aka":["LymphGen-directed first-line therapy","Genetic subtype-directed treatment in diffuse large B-cell lymphoma"],"tldr":"Three genetic classifications of the commonest aggressive lymphoma exist and none of them yet decides anyone's treatment. The trial that would change that has not been run.","summary":"The obstacles are concrete rather than conceptual. Comprehensive classification needs copy number and structural variants as well as mutations, which routine panels do not generate; a turnaround time short enough to decide first-line treatment in an aggressive lymphoma means days, not weeks; and a proportion of tumours remain unclassified by design. Any trial has to report that proportion honestly, because a classifier that works on two-thirds of patients is a different clinical proposition from one that works on all of them. The training cohorts were also largely of European ancestry, which is a validation gap rather than a flaw.","asOf":"2026-10-01","links":[],"tags":["lymphoma-evidence"],"related":["lymphoma-roadmap"],"cancers":["dlbcl","non-hodgkin-lymphoma"],"sections":["diagnostics","targeted-therapy"],"technologies":["wes-wgs","ngs"],"targets":["myd88","cd79b","bcl2","btk","ezh2"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["cell-of-origin"],"trials":[],"people":[],"bottlenecks":["b-biomarker-validation","b-trial-design","b-translational-valley"],"keyPapers":["paper-wright-lymphgen-genetic-subtypes-dlbcl-cancer-cell-2020","paper-schmitz-genetics-pathogenesis-dlbcl-nejm-2018","paper-chapuy-molecular-subtypes-dlbcl-nat-med-2018","paper-phoenix-ibrutinib-r-chop-non-gcb-dlbcl-jco-2019"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Assigning first-line treatment in diffuse large B-cell lymphoma by LymphGen genetic subtype improves progression-free survival over assigning it by cell-of-origin immunohistochemistry or by giving everyone R-CHOP.","rationale":"Schmitz showed that two of the four genetic subtypes, MCD and BN2, depend on chronic active B-cell receptor signalling, which Bruton tyrosine kinase inhibitors block, and that outcomes differ sharply between subtypes after immunochemotherapy. PHOENIX, which selected by the non-germinal-centre immunohistochemistry phenotype rather than by genetics, failed overall while producing long remissions in a subgroup. Wright's LymphGen tool makes per-patient classification possible with a probability attached. The pieces exist; nobody has put them in a randomised trial of first-line treatment.","test":"A randomised first-line trial in diffuse large B-cell lymphoma with comprehensive genomic profiling at diagnosis, assigning treatment by LymphGen subtype in the experimental arm (a Bruton tyrosine kinase inhibitor or a BCL2 inhibitor added to R-CHOP for the subtypes predicted to benefit, standard R-CHOP for the rest) against R-CHOP for everyone, powered on progression-free survival, with the proportion of tumours successfully classified reported as a co-primary feasibility endpoint.","maturity":"preclinical-evidence","actor":"research","cost":"large","horizonYears":8},{"id":"idea-tr1-community-site-quota","kind":"idea","name":"At least a third of pivotal-trial sites in community and rural settings","aka":[],"tldr":"Most cancer patients are treated outside big academic hospitals, but most trials are run inside them. Requiring a share of sites to be community practices would bring trials to where patients are.","summary":"Regulators and public funders would expect registrational trials to open at least 30 percent of sites in community oncology practices and non-metropolitan hospitals, supported by hub-and-spoke oversight from an academic centre (the NCORP model). Sponsors report site mix in the application and diversity plan.","asOf":"2026-09-08","links":[{"label":"NCI Community Oncology Research Program","url":"https://ncorp.cancer.gov/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["nci"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-enrolment","b-trial-diversity"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Trials meeting a community-site share will enrol a population closer to the disease's real-world age, race and rurality distribution, and will not have worse data quality by monitoring metrics.","rationale":"NCORP trials enrol more rural and minority patients than academic-only trials; community practices treat the majority of US cancer patients but host a minority of industry trials.","test":"Compare demographic representativeness and query rates between industry trials above and below the community-site threshold, using FDA Drug Trials Snapshots and sponsor data.","maturity":"speculative","actor":"regulator","cost":"small","horizonYears":3},{"id":"idea-ecdna-targeting","kind":"idea","name":"Attack extrachromosomal DNA, the engine of oncogene amplification","aka":[],"tldr":"Aggressive glioblastomas, sarcomas and gastric cancers keep amplified cancer genes such as EGFR, MYC, MDM2 and CDK4 on free-floating DNA circles (ecDNA) whose copy number rises and falls quickly, letting the tumour dial resistance up and down. Cells carrying ecDNA depend on CHK1, giving a first drug target.","summary":"ecDNA carries EGFR, MYC, MDM2, and CDK4 amplicons in glioblastoma, sarcoma, and gastric cancer, associates with shorter survival, and enables rapid drug resistance by copy-number fluctuation. The eDyNAmiC Cancer Grand Challenge team reported CHK1 dependence and transcription-replication conflicts in ecDNA+ cells (2024).","asOf":"2026-09-08","links":[{"label":"Turner et al., Extrachromosomal oncogene amplification drives tumour evolution and genetic heterogeneity (Nature 2017)","url":"https://doi.org/10.1038/nature21356"}],"tags":["mechanism","open-question"],"related":[],"cancers":["glioblastoma","sarcoma","gastric"],"sections":[],"technologies":["wes-wgs","liquid-biopsy"],"targets":["egfr","cdk4-6"],"drugs":[],"companies":[],"institutions":["stanford","cruk"],"pathways":["chromosomal-instability","replication-stress","clonal-evolution"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-turner-nature","paper-egfr-gastric-eur-j-cancer-2001","paper-egfr-glioblastoma-mol-oncol-2018","paper-egfr-glioblastoma-sci-signal-2009"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"ecDNA-positive tumours are selectively sensitive to CHK1 inhibition combined with the amplified-oncogene inhibitor, and ecDNA status detectable by WGS or cfDNA identifies responders.","rationale":"Preclinical CHK1 sensitivity, an ecDNA detection assay (AmpliconArchitect) applicable to routine WGS, and the failure of oncogene inhibitors alone in ecDNA-driven tumours.","test":"Phase 1/2 of a CHK1 inhibitor plus targeted agent in ecDNA-positive EGFR-amplified glioblastoma and MDM2/CDK4-amplified sarcoma, with ecDNA burden in cfDNA as a pharmacodynamic marker.","maturity":"preclinical-evidence"},{"id":"idea-bio1-paralog-synthetic-lethality","kind":"idea","name":"Attack the backup copy when a tumour has lost the original gene","aka":[],"tldr":"Tumours often lose one of a pair of near-identical genes. They then depend entirely on the remaining copy, which a drug can block, killing only the cancer.","summary":"SMARCA4-mutant cancers depend on SMARCA2; MTAP-deleted cancers depend on PRMT5 in a methylthioadenosine-dependent manner; other paralog pairs (for example ARID1A/ARID1B, ENO1/ENO2) show the same logic. Paralog dependencies are the most systematic way to exploit tumour-suppressor loss, which is otherwise undruggable. Selective SMARCA2 degraders and MTA-cooperative PRMT5 inhibitors have reached the clinic.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The undruggable drivers): Dang et al., Drugging the 'undruggable' cancer targets (Nature Reviews Cancer 2017)","url":"https://doi.org/10.1038/nrc.2017.36"}],"tags":[],"related":["idea-mtap-prmt5-mesothelioma"],"cancers":[],"sections":[],"technologies":["crispr-screens","synthetic-lethality-approaches","protac-degrader"],"targets":[],"drugs":[],"companies":[],"institutions":["broad-institute","icr-london"],"pathways":[],"terms":["synthetic-lethality"],"trials":[],"people":[],"bottlenecks":["b-undruggable-targets"],"keyPapers":["paper-dang-nat-rev-cancer"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A genome-wide paralog dependency map across 500 cell lines yields at least ten new pairs where loss-of-function in the tumour creates a greater than five-fold selective dependency confirmed in vivo.","rationale":"Tumour suppressor loss is more common than oncogene activation but has almost no direct therapies; paralog buffering converts loss into a positive drug target, exactly as PARP inhibition did for BRCA loss.","test":"Dual-guide CRISPR paralog screens in a large line panel with matched genotype annotation; validate the top hits in isogenic pairs and PDX models before chemistry investment.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":5},{"id":"idea-tr2-arrive-audit","kind":"idea","name":"Audit animal studies for randomisation and blinding, published by institution","aka":[],"tldr":"Most mouse studies of cancer drugs do not randomise animals or blind the people measuring tumours, which inflates results. Checking and publishing which institutions do it properly would change behaviour.","summary":"The ARRIVE guidelines set minimum reporting standards for animal research, but compliance remains low and unenforced. Systematic reviews show that unblinded, unrandomised animal studies overestimate effects. Funders could commission annual audits of a random sample of animal studies they supported, scoring randomisation, blinding, sample-size justification and reporting, and publish scores by institution.","asOf":"2026-09-08","links":[{"label":"ARRIVE guidelines","url":"https://arriveguidelines.org/"}],"tags":[],"related":["idea-tr2-animal-power-mandate","idea-tr2-multilab-preclinical"],"cancers":[],"sections":[],"technologies":["pdx-models"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-reproducibility","b-preclinical-models"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Institutions whose scores are published will improve compliance with randomisation and blinding to above 80% within three years, from the 20 to 40% typically found in audits.","rationale":"Public institutional scores worked for clinical trial transparency; animal research has the same structure of diffuse responsibility that public reporting fixes.","test":"Audit 500 funded animal studies across 20 institutions; publish; re-audit after two years.","maturity":"early-clinical","actor":"philanthropy","cost":"small","horizonYears":2},{"id":"idea-acc-tumour-board-implementation-audit","kind":"idea","name":"Audit whether tumour board recommendations were actually carried out","aka":[],"tldr":"Hospitals hold weekly meetings to decide each patient's plan but rarely check what happened afterwards. A simple loop that records the recommendation and checks it against what was done would catch dropped plans.","summary":"Studies suggest that a meaningful minority of multidisciplinary team recommendations are not implemented, for reasons ranging from patient choice to lost referrals, and few boards track this. Recording each recommendation as structured data and reconciling it automatically with subsequent orders and treatment records would produce an implementation rate per team, with reasons for deviation, closing the loop on the most important decision point in cancer care.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Fragmented care and guideline gaps): Hanna et al., Mortality due to cancer treatment delay: systematic review and meta-analysis (BMJ 2020)","url":"https://doi.org/10.1136/bmj.m4087"}],"tags":[],"related":["idea-acc-guideline-concordance-dashboards"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-care-fragmentation"],"keyPapers":["paper-hanna-bmj"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Boards that receive quarterly implementation audits will reduce unexplained non-implementation of recommendations by at least half within a year.","rationale":"Closing feedback loops is basic quality engineering; multidisciplinary boards are one of the few places in medicine where the decision is documented but the outcome is not systematically checked.","test":"Introduce structured recommendation capture and reconciliation in ten hospitals and measure implementation rates and reasons over four quarters.","maturity":"speculative","actor":"clinic","cost":"small","horizonYears":1},{"id":"idea-moon-automated-combination-discovery","kind":"idea","name":"Automated combination discovery: patient-sample screens feeding Bayesian platform trials","aka":[],"tldr":"There are far more possible drug combinations than can ever be tried in patients. Test thousands on living samples of real tumours, then feed only the winners into adaptive trials.","summary":"The combination space of approved and investigational cancer drugs is astronomically large; combinations reach the clinic through intuition and commercial convenience. Functional precision medicine (ex vivo drug testing on patient cells, EXALT trial in haematological malignancies) and high-throughput organoid screening make empirical combination discovery on patient material feasible. The proposal is an integrated pipeline: standardised ex vivo combination screens on fresh samples from trial participants, machine learning to prioritise synergistic and resistance-preventing pairs, and a standing Bayesian platform trial that adds and drops combination arms based on pipeline output.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Too many combinations to test): Palmer & Sorger, Combination cancer therapy can confer benefit via patient-to-patient variability without drug additivity or synergy (Cell 2017)","url":"https://doi.org/10.1016/j.cell.2017.11.009"}],"tags":[],"related":["idea-organoid-guided-adc"],"cancers":["aml","colorectal"],"sections":[],"technologies":["functional-drug-testing","organoids","ai-drug-design"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["basket-umbrella-platform"],"trials":[],"people":[],"bottlenecks":["b-combination-space","b-preclinical-models"],"keyPapers":["paper-palmer-cell"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Pipeline-prioritised combinations achieve response rates in the platform at least double those of historically selected combinations in the same settings.","rationale":"Empirical screening beat rational design in antibiotics and in EXALT; connecting the screen directly to a trial closes the loop that has been missing.","test":"Run the pipeline in relapsed acute myeloid leukaemia and metastatic colorectal cancer for three years; compare platform response rates with contemporaneous conventional combination trials.","maturity":"preclinical-evidence","actor":"research","cost":"large","horizonYears":6},{"id":"idea-data-retraction-propagation","kind":"idea","name":"Automatic flagging of retracted or corrected evidence in guidelines and decision support","aka":[],"tldr":"When a study is retracted or corrected, every guideline and software tool that relied on it would be alerted automatically, so wrong evidence stops influencing care.","summary":"Retracted papers continue to be cited for years; guidelines and decision tools rarely re-check their evidence base. With structured citations in computable guidelines and an evidence graph, retraction and correction notices (Retraction Watch database, Crossref) can be matched to every recommendation that depends on the affected study, triggering review. The proposal builds and funds that matching service.","asOf":"2026-09-08","links":[{"label":"Retraction Watch Database","url":"https://retractionwatch.com/retraction-watch-database-user-guide/"}],"tags":[],"related":["idea-data-computable-living-guidelines"],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-knowledge-diffusion","b-reproducibility"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Automatic propagation will reduce the time from retraction to guideline review from years to weeks and will identify recommendations resting on retracted evidence that are currently unnoticed.","rationale":"Retraction Watch and Crossref make notices machine-readable; the gap is that guidelines do not maintain machine-readable citation lists, which computable guidelines would fix.","test":"Match the Retraction Watch database against citations in three major oncology guidelines; count affected recommendations; run the service prospectively for one year.","maturity":"speculative","actor":"engineering","cost":"small","horizonYears":1},{"id":"idea-prev-reflex-germline-testing","kind":"idea","name":"Automatic germline testing for every cancer type where it changes care","aka":[],"tldr":"Anyone with ovarian, pancreatic, metastatic prostate or mismatch-repair-deficient colorectal cancer should be tested for inherited mutations, yet testing rates fall well short. Making it an automatic, opt-out laboratory step triggered by pathology, as reflex mismatch-repair testing already is, would close the gap.","summary":"Anyone with ovarian, pancreatic, metastatic prostate or mismatch-repair-deficient colorectal cancer should have germline testing, but testing rates fall well short, so this idea makes it an automatic opt-out laboratory step triggered by pathology, as reflex MMR and MSI testing already is, mainstreamed by oncologists with genetics support only for positives. Reflex mismatch-repair testing succeeded and mainstreaming trials show oncologists can consent patients. The aim is near-universal testing in eligible groups and proportionally more cascade testing of relatives. The test is health-system implementation with monthly testing-rate dashboards. Being tested at scale, it addresses the bottleneck Inherited risk is mostly unidentified.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Inherited risk is mostly unidentified): Childers et al., National estimates of genetic testing in women with breast or ovarian cancer (JCO 2017)","url":"https://doi.org/10.1200/JCO.2017.73.6314"}],"tags":[],"related":["prostate-roadmap","idea-prostate-hrr-testing-at-metastatic-diagnosis"],"cancers":["ovarian","pancreatic","prostate","colorectal"],"sections":["prevention","diagnostics"],"technologies":["germline-testing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["germline-vs-somatic","msi"],"trials":[],"people":[],"bottlenecks":["b-hereditary-risk"],"keyPapers":["paper-childers-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Reflex opt-out testing raises germline testing to at least 90% in eligible groups and increases cascade testing of relatives proportionally.","rationale":"Reflex mismatch-repair testing succeeded, and mainstreaming trials show oncologists can consent patients.","test":"Health-system implementation with monthly testing-rate dashboards.","maturity":"being-tested-at-scale","actor":"clinic","cost":"small","horizonYears":2},{"id":"idea-fund-shelved-asset-escrow","kind":"idea","name":"Automatic offer of shelved cancer assets to non-profits after two years","aka":[],"tldr":"When a company stops developing a cancer drug for business rather than safety reasons and leaves it idle for two years, it would be obliged to offer the rights, data package and remaining drug supply to qualified non-profit or academic developers on pre-set terms, keeping the right to resume. This turns the stalled-asset registry's listing into a duty.","summary":"A legal or funder-imposed condition (for example on drugs that received public research funding, orphan designation or tax credits) that oncology assets discontinued for non-safety reasons and not actively developed for two years must be offered for licence to qualified non-profit or academic developers on pre-set terms (non-exclusive for research, exclusive for defined rare indications, modest royalties on commercialisation). Data packages and remaining drug supply are included. Companies retain rights to resume. This complements the stalled-asset registry by creating a duty, not just a listing.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Secrecy and intellectual property block collaboration): Danchev et al., Evaluation of data sharing after implementation of the ICMJE data sharing statement requirement (JAMA Netw Open 2021)","url":"https://doi.org/10.1001/jamanetworkopen.2020.33972"}],"tags":[],"related":["idea-fund-stalled-asset-registry","idea-fund-nonprofit-pharma","idea-fund-repurposing-indication-exclusivity","tiragolumab","magrolimab"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-ip-collaboration","b-translational-valley","b-rare-cancers"],"keyPapers":["paper-danchev-jama-netw-open"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"An escrow duty leads to at least ten shelved oncology assets entering non-profit or academic development within three years and at least one reaching a registration trial in a rare or paediatric indication within six.","rationale":"Many discontinued assets have adequate safety data and mechanistic rationale in indications the owner never pursued; academic groups routinely identify such assets but cannot obtain them. Use-it-or-lose-it provisions exist in patent law (compulsory licensing for non-working) and in orphan drug regulation (revocation for insufficient supply).","test":"Apply the condition to publicly co-funded assets in one jurisdiction and track offers, licences and subsequent trials over three years.","maturity":"speculative","actor":"policy","cost":"small","horizonYears":3},{"id":"idea-acc-automatic-early-palliative-triggers","kind":"idea","name":"Automatic palliative care referral triggered by diagnosis, not by decline","aka":[],"tldr":"Palliative care given from the start of treatment for advanced cancer improves quality of life and may extend it. Instead of waiting for an oncologist to remember, the system should refer automatically when the diagnosis is recorded.","summary":"Temel and colleagues showed in 2010 that early palliative care in metastatic lung cancer improved quality of life, mood, and survival, and subsequent trials confirmed benefits across cancers. Referral remains late and inconsistent. Electronic triggers (stage IV diagnosis of defined cancers, second-line therapy start, unplanned admission) that generate a default referral unless declined would make early integration the norm.","asOf":"2026-09-08","links":[{"label":"Temel et al., NEJM 2010","url":"https://www.nejm.org/doi/full/10.1056/NEJMoa1000678"}],"tags":[],"related":[],"cancers":["nsclc","pancreatic","gastric"],"sections":["supportive-care"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-palliative","b-care-fragmentation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Automatic triggers will raise the proportion of patients with metastatic lung, pancreatic, and gastric cancer seen by palliative care within eight weeks of diagnosis from under 30% to above 75%, and reduce chemotherapy in the last 14 days of life.","rationale":"Default enrolment outperforms clinician-initiated referral in every domain where it has been tested; the evidence for early palliative care is Level 1.","test":"A stepped-wedge trial across 15 centres with time to palliative contact, end-of-life quality indicators, and patient-reported quality of life as endpoints.","maturity":"being-tested-at-scale","actor":"clinic","cost":"small","horizonYears":2},{"id":"idea-reg-market-expansion-repricing","kind":"idea","name":"Automatic price cuts when a cancer drug's approved indications and volumes expand","aka":[],"tldr":"When a cancer drug is approved for more uses, the company sells far more of it but the price stays the same. Japan cuts prices automatically when sales balloon; others should too.","summary":"Japan's market expansion repricing rule lowers the reimbursement price when a drug's sales exceed forecasts by a defined margin, and was applied to nivolumab, whose price was cut by half in 2017 after expansion beyond melanoma. Most other systems renegotiate slowly or not at all as indications multiply. The proposal is a rule-based repricing schedule in other public systems: price falls by a published formula when cumulative approved indications or annual volume cross thresholds, reflecting the lower per-unit development cost and the fact that later indications rely on the same molecule.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Prices and value): Prasad, De Jesús & Mailankody, The high price of anticancer drugs: origins, implications, barriers, solutions (Nat Rev Clin Oncol 2017)","url":"https://doi.org/10.1038/nrclinonc.2017.31"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":["nivolumab","pembrolizumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-drug-pricing"],"keyPapers":["paper-prasad-nat-rev-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Rule-based repricing reduces spend on multi-indication oncology drugs by at least 20% within three years of adoption without reducing the number of new indications filed in that market.","rationale":"A drug's development cost does not scale with its indications, so returns balloon as indications expand; a predictable formula avoids case-by-case negotiation and gives manufacturers certainty.","test":"Compare spend trajectories for checkpoint inhibitors in Japan with those in comparable markets without expansion repricing; adopt a formula in one further market and measure spend and filing behaviour.","maturity":"being-tested-at-scale","actor":"payer","cost":"small","horizonYears":3},{"id":"idea-reg-orphan-designation-reciprocity","kind":"idea","name":"Automatic reciprocity of orphan and rare-paediatric designations between regulators","aka":[],"tldr":"A rare cancer drug designated 'orphan' in the US must reapply in Europe, Japan and elsewhere. Recognising each other's decisions would save small companies months.","summary":"Orphan designation (FDA, EMA, MHLW, others) grants fee waivers, protocol assistance and exclusivity, and is applied for separately with different prevalence thresholds and evidence formats. FDA and EMA offer a common application form but decide independently. The proposal is reciprocal recognition: a designation from one stringent regulator is accepted by partners on notification, with local prevalence data required only where the condition's epidemiology plausibly differs.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Regulatory divergence between regions): FDA Oncology Center of Excellence, Project Orbis","url":"https://www.fda.gov/about-fda/oncology-center-excellence/project-orbis"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-regulatory-fragmentation","b-rare-cancers"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Reciprocity increases the number of rare-cancer programmes holding designations in all major regions by at least 30% and shortens time to designation in the second region from months to weeks.","rationale":"Designation is largely a prevalence calculation; rare cancers are rare everywhere. The administrative burden falls disproportionately on small biotechs and academic sponsors, which run most rare-cancer programmes.","test":"Pilot reciprocity for oncology designations between FDA, EMA and MHRA for two years; count programmes designated in all three and time to second designation before and after.","maturity":"speculative","actor":"regulator","cost":"small","horizonYears":2},{"id":"idea-data-automatic-outcome-linkage","kind":"idea","name":"Automatic weekly linkage of cancer registries to deaths, prescriptions and imaging","aka":[],"tldr":"Connect the cancer registry to death records, pharmacy records and scan reports automatically every week, so we always know what happened to every patient without anyone filling in a form.","summary":"Most registries capture diagnosis well and outcomes poorly, with follow-up lagging years. Nordic registries and England's National Disease Registration Service show that deterministic linkage to death, hospital episode, prescribing and imaging records makes near-complete outcome capture routine. The proposal funds automated pipelines with statutory access and weekly refresh in every registry country, plus derivation of progression proxies from imaging report text using validated NLP.","asOf":"2026-09-08","links":[{"label":"NHS National Disease Registration Service","url":"https://digital.nhs.uk/ndrs"}],"tags":[],"related":["seer"],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["real-world-evidence"],"trials":[],"people":[],"bottlenecks":["b-data-silos","b-real-world-evidence"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Weekly automated linkage reduces registry outcome latency from more than two years to under three months and raises treatment-outcome completeness above 95 percent.","rationale":"Where linkage is statutory and automated (Denmark, Sweden, England), registries are the backbone of real-world evidence; elsewhere they are diagnosis counts. The difference is legal access and engineering, not science.","test":"In one registry without current linkage, build the pipeline and compare outcome completeness and latency before and after over two years; validate NLP-derived progression against chart review in 1,000 patients.","maturity":"being-tested-at-scale","actor":"data","cost":"medium","horizonYears":2},{"id":"idea-tr2-outcome-switching-monitor","kind":"idea","name":"Automatically detect when a trial changes its outcomes after the fact","aka":[],"tldr":"Trials sometimes quietly swap the outcome they promised to measure for one that looks better. Software can compare the registered plan with the published paper and flag the switch.","summary":"The COMPare project manually compared registered and published outcomes in five top journals and found widespread undisclosed switching. Registry entries and publications are now structured enough for automated comparison, and pre-specified statistical analysis plans are increasingly public. A continuously running monitor that flags outcome discrepancies in oncology trials, notifies journals and posts findings publicly would deter switching.","asOf":"2026-09-08","links":[{"label":"COMPare trials project","url":"https://compare-trials.org/"}],"tags":[],"related":["clinicaltrials-gov","pubmed-europepmc","idea-tr2-automated-stats-check"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-negative-results","b-trial-design"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Public flagging reduces undisclosed primary outcome switching in oncology trials from the roughly 30% documented in audits to under 10% within three years.","rationale":"COMPare showed that journals correct when confronted with evidence. Automation makes the confrontation systematic rather than sporadic.","test":"Build the monitor over ClinicalTrials.gov and PubMed; audit its precision manually on 200 trials; publish quarterly reports and measure the switching rate.","maturity":"early-clinical","actor":"data","cost":"small","horizonYears":1},{"id":"idea-moon-closed-loop-adaptive-therapy","kind":"idea","name":"Autonomous closed-loop adaptive therapy driven by blood tests and evolutionary models","aka":[],"tldr":"Rather than giving the same dose until the cancer grows, measure tumour DNA in blood every few weeks and let a validated algorithm raise, lower, pause or switch drugs to keep the cancer suppressed for longer.","summary":"Adaptive therapy trials in prostate cancer (PSA-guided abiraterone cycling at Moffitt) suggest that modulating dose to maintain competition between sensitive and resistant cells can extend control. Circulating tumour DNA now allows frequent, clone-resolved monitoring across cancers. The proposal is a closed-loop system: serial ctDNA and imaging feed an evolutionary model that recommends dose and drug changes under pre-specified rules, with clinician oversight, tested first in oncogene-driven lung cancer and hormone-sensitive prostate cancer.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Acquired resistance to every therapy): Soria et al., Osimertinib in untreated EGFR-mutated NSCLC (FLAURA, NEJM 2018)","url":"https://doi.org/10.1056/NEJMoa1713137"}],"tags":[],"related":[],"cancers":["nsclc","prostate"],"sections":[],"technologies":["liquid-biopsy","kinase-inhibitors"],"targets":[],"drugs":["osimertinib"],"companies":[],"institutions":["moffitt"],"pathways":[],"terms":["ctdna","resistance"],"trials":["adaura","flaura","flaura2","laura","nct06417814"],"people":[],"bottlenecks":["b-resistance","b-dose-optimisation","b-ai-validation"],"keyPapers":["paper-flaura-nejm-2018","paper-osimertinib-nsclc-n-engl-j-med-2017","paper-osimertinib-nsclc-n-engl-j-med-2020"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Algorithm-guided adaptive dosing extends time to treatment failure by at least 30% over continuous standard dosing with lower cumulative drug exposure and toxicity.","rationale":"Resistance is an evolutionary process; continuous maximum dosing selects for it. Frequent measurement plus rule-based modulation is how control engineering handles adaptive adversaries.","test":"Randomised phase 2 of closed-loop adaptive versus standard continuous therapy in EGFR-mutant lung cancer on osimertinib, with time to failure primary and cumulative dose and toxicity secondary.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":6},{"id":"idea-moon-ban-unproven-therapy-ads","kind":"idea","name":"Ban and enforce against paid advertising of unproven cancer treatments","aka":[],"tldr":"Make it illegal and technically impossible to buy adverts for cancer cures that have not been proven, and hold platforms responsible for enforcement.","summary":"Many jurisdictions prohibit advertising cancer cures in principle (for example the UK Cancer Act 1939) but enforcement online is minimal and platforms accept paid promotion of unproven clinics and supplements. The proposal is explicit legislation covering digital advertising, platform liability for paid cancer treatment promotion without regulatory authorisation, an automated flagging pipeline, and regular published enforcement statistics.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Misinformation and unproven therapies): Johnson et al., Cancer misinformation and harmful information on Facebook and other social media (JNCI 2022)","url":"https://doi.org/10.1093/jnci/djab141"}],"tags":[],"related":["idea-moon-unproven-clinic-registry"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-misinformation"],"keyPapers":["paper-johnson-j-natl-cancer-inst"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Enforcement removes the majority of paid unproven-cure advertising within a year and reduces referrals to and spending on unproven clinics.","rationale":"Paid reach is the accelerant of unproven-therapy marketing; removing it is more tractable than moderating organic speech and has clear legal precedent.","test":"Audit paid cancer-treatment adverts before and after enforcement in one jurisdiction; measure ad volume, clinic web traffic and patient-reported exposure.","maturity":"early-clinical","actor":"policy","cost":"small","horizonYears":1},{"id":"idea-prev-commercial-sunbed-ban","kind":"idea","name":"Ban commercial sunbeds","aka":[],"tldr":"Sunbeds cause melanoma, especially when used young. Australia and Brazil have banned them. Other countries should follow and measure the effect.","summary":"Sunbeds cause melanoma, especially when used young, and IARC classifies UV tanning devices as Group 1 carcinogens, so this idea bans commercial sunbeds in the remaining high-use countries, much of Europe and the US, following Australia and Brazil. Each ban would carry a pre-planned evaluation of melanoma incidence in adults under 40. The causal evidence is strong, the policy precedent exists and the cost is negligible. The test is an interrupted time series against non-adopting comparators. Being tested at scale, it addresses the bottleneck Prevention we already have is not deployed and links to the melanoma record and IARC.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Prevention we already have is not deployed): Islami et al., Proportion of cancer attributable to modifiable risk factors (CA 2018)","url":"https://doi.org/10.3322/caac.21440"}],"tags":[],"related":[],"cancers":["melanoma"],"sections":["prevention"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["iarc"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption"],"keyPapers":["paper-islami-ca-cancer-j-clin"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A commercial sunbed ban reduces melanoma incidence in adults under 40 by at least 10% within 15 years.","rationale":"Strong causal evidence, policy precedent, and negligible cost.","test":"Run an interrupted time series against non-adopting comparators.","maturity":"being-tested-at-scale","actor":"policy","cost":"small","horizonYears":10},{"id":"idea-prev-genetic-non-discrimination-insurance","kind":"idea","name":"Ban life and disability insurers from using genetic results","aka":[],"tldr":"Fear of losing insurance is a top barrier to genetic testing in surveys. Extending non-discrimination law to life and disability cover, as Canada's 2017 Genetic Non-Discrimination Act does and the US law does not, would remove that fear and raise cascade testing in families.","summary":"Fear of losing insurance deters people from genetic testing, so this idea extends non-discrimination law to life and disability cover in countries that lack it, as Canada's Genetic Non-Discrimination Act of 2017 does, whereas the US Genetic Information Nondiscrimination Act excludes those products. Surveys consistently cite insurance fear as a top barrier to testing, so the aim is higher cascade and population testing uptake. The test is a difference-in-differences comparison across jurisdictions before and after legal change. Speculative in maturity, it addresses the bottlenecks Inherited risk is mostly unidentified and Prevention we already have is not deployed, and links to germline testing.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Inherited risk is mostly unidentified): Childers et al., National estimates of genetic testing in women with breast or ovarian cancer (JCO 2017)","url":"https://doi.org/10.1200/JCO.2017.73.6314"}],"tags":[],"related":[],"cancers":[],"sections":["prevention"],"technologies":["germline-testing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-hereditary-risk","b-prevention-adoption"],"keyPapers":["paper-childers-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Legal protection increases cascade and population testing uptake by at least 10 percentage points.","rationale":"Surveys consistently cite insurance fear as a top barrier to testing.","test":"Difference-in-differences comparison across jurisdictions before and after legal change.","maturity":"speculative","actor":"policy","cost":"small","horizonYears":3},{"id":"idea-bio1-multiregion-blocks-default","kind":"idea","name":"Bank three spatially separate tumour blocks from every resection","aka":[],"tldr":"Hospitals usually keep one piece of a removed tumour. Keeping three pieces from different parts would show how varied the tumour is, at almost no extra cost.","summary":"TRACERx showed that a single region misses subclonal drivers and under-calls copy-number heterogeneity in a large share of lung cancers. Pathology protocols could mandate three or more spatially annotated blocks (core, edge, invasive front) frozen and formalin-fixed for every resected solid tumour, with the region map stored with the specimen. The marginal cost is technician time; the payoff is a national multi-region resource attached to outcomes.","asOf":"2026-09-08","links":[{"label":"TRACERx (NCT01888601)","url":"https://clinicaltrials.gov/study/NCT01888601"}],"tags":[],"related":[],"cancers":["nsclc","colorectal","rcc"],"sections":[],"technologies":["wes-wgs","cgp"],"targets":[],"drugs":[],"companies":[],"institutions":["francis-crick","cruk"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-tumor-heterogeneity","b-data-silos"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Routine three-block banking changes the reported driver or clonality status in at least 10 percent of resected tumours and improves recurrence prediction over single-block profiling.","rationale":"Multi-region sequencing consistently reveals branch drivers and chromosomal instability that single biopsies miss; TRACERx and PCAWG show heterogeneity metrics are prognostic. Banking is cheap; sequencing can follow later.","test":"Two-year pilot in five surgical centres: implement the protocol, sequence a random 500-case subset, and measure the discordance rate between single-block and three-block calls and the improvement in relapse prediction.","maturity":"preclinical-evidence","actor":"clinic","cost":"small","horizonYears":3},{"id":"idea-bio2-survivor-plasma-biobank","kind":"idea","name":"Bank yearly blood from cancer survivors so future tests can be validated","aka":[],"tldr":"To prove a leftover-cancer test works you need blood taken years before relapse. Collecting and freezing yearly samples now makes every future test testable.","summary":"Every new MRD or early detection assay needs pre-diagnostic or pre-relapse serial specimens, which take years to accumulate and cannot be created retrospectively. A prospective survivor cohort of 50,000 people banking annual plasma, with registry-linked outcomes and open access rules, would become the shared validation substrate for the whole field.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Dormant cells and minimal residual disease): Tie et al., ctDNA analysis guiding adjuvant therapy in stage II colon cancer (NEJM 2022)","url":"https://doi.org/10.1056/NEJMoa2200075"}],"tags":[],"related":["seer","cbioportal"],"cancers":[],"sections":[],"technologies":["liquid-biopsy","mrd-testing","mced"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["mrd","ctdna"],"trials":[],"people":[],"bottlenecks":["b-dormancy-mrd","b-data-silos","b-early-detection"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A serial survivor plasma bank with linked outcomes shortens the validation cycle for a new MRD assay from five years to under one, and is used by at least ten independent developers within five years of opening.","rationale":"The UK Biobank and PLCO-style cohorts demonstrate that pre-event specimen collections become disproportionately valuable over time and are impossible to replicate quickly. Survivors are highly motivated donors and are already in follow-up pathways.","test":"Pilot in 2,000 survivors at high recurrence risk with annual draws for three years; measure retention, cost per sample-year, and number of external validation studies enabled.","maturity":"speculative","actor":"data","cost":"medium","horizonYears":8},{"id":"idea-tr2-reagent-lot-ledger","kind":"idea","name":"Barcode every reagent lot so batch effects can be traced across experiments and labs","aka":[],"tldr":"Results can change when a supplier changes a batch of serum, antibody or growth factor. Recording which batch was used in each experiment, in a shared ledger, would let these effects be spotted.","summary":"Lot-to-lot variation in serum, media supplements, antibodies and enzymes is a recognised but untracked source of irreproducibility. A shared, machine-readable ledger of reagent lots (vendor, catalogue and lot number, hashed) linked to experiments and publications, populated by lab inventory software and vendor APIs, would let batch effects be detected across the community and would let vendors be held accountable for problem lots.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Preclinical results do not reproduce): Errington et al., Investigating the replicability of preclinical cancer biology (eLife 2021)","url":"https://doi.org/10.7554/eLife.71601"}],"tags":[],"related":["idea-tr2-cell-line-passport","idea-tr2-antibody-validation-mandate"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-reproducibility"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Ledger analysis will identify at least one widely used reagent lot associated with anomalous results across multiple laboratories within two years, and its identification will explain a documented replication failure.","rationale":"Supply-chain traceability is standard in manufacturing and food safety; research reagents have no equivalent despite comparable stakes.","test":"Implement lot capture in two inventory tools across twenty labs; link to published experiments; search for lot-associated anomalies.","maturity":"speculative","actor":"engineering","cost":"small","horizonYears":2},{"id":"idea-bio1-barcoded-avatars-clonal-fitness","kind":"idea","name":"Barcode patient-derived tumours to watch which clones win under each drug","aka":[],"tldr":"Tag every cell in a patient's lab-grown tumour with a unique DNA label, give it a drug, and read the labels to see which cells survive. This predicts which resistant clone will emerge.","summary":"Lentiviral cellular barcoding of organoids or PDX models allows quantitative clonal tracking under therapy. Applied to patient avatars before treatment, it would measure the pre-existing resistant clone fraction and fitness under candidate drugs, prioritising combinations that suppress all high-fitness clones rather than the bulk.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Tumour heterogeneity and clonal evolution): Gerlinger et al., Intratumor heterogeneity and branched evolution (NEJM 2012)","url":"https://doi.org/10.1056/NEJMoa1113205"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["organoids","pdx-models","crispr-screens"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["resistance"],"trials":[],"people":[],"bottlenecks":["b-tumor-heterogeneity","b-preclinical-models"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Barcoded avatar clonal dynamics predict the dominant resistance clone found in the patient's progression biopsy in most cases, and drug combinations chosen to suppress all barcoded winners extend avatar time-to-regrowth compared with bulk-response-chosen combinations.","rationale":"Barcoding studies in cell lines and PDX (for example in breast and lung models) show that resistance often arises from rare pre-existing clones whose identity is stable and predictable, not from random de novo events.","test":"Barcode 30 patient-derived models with matched clinical follow-up, treat with the patient's actual regimen, and compare the barcoded winner genotype with the patient's progression biopsy.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":4},{"id":"idea-tr1-shrinkage-subgroup-analysis","kind":"idea","name":"Bayesian shrinkage for subgroup claims to stop false 'works in this group' stories","aka":[],"tldr":"Trials look at dozens of patient subgroups and some will look good by chance. A statistical method that pulls extreme subgroup results toward the overall result would make these claims more honest.","summary":"Forest plots of subgroup effects are replaced or accompanied by hierarchical Bayesian shrinkage estimates, in which each subgroup effect is partially pooled toward the overall effect according to its precision. Regulators require shrunken estimates for any subgroup claim in a label and journals require them in publications.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Trial design, endpoints and cost): Davis et al., Availability of evidence of benefits on survival and quality of life of cancer drugs approved by EMA 2009-13 (BMJ 2017)","url":"https://doi.org/10.1136/bmj.j4530"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["hazard-ratio"],"trials":[],"people":[],"bottlenecks":["b-trial-design","b-negative-results"],"keyPapers":["paper-davis-bmj"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Shrinkage-based subgroup reporting will reduce the number of subgroup-driven label restrictions or expansions that are later reversed, and will improve replication of subgroup effects in subsequent trials.","rationale":"Naive subgroup estimates are noisy and biased toward extremes when selected; shrinkage is the standard remedy in other fields and would have avoided several well-known oncology subgroup reversals.","test":"Re-analyse subgroup claims from past label decisions with shrinkage and check which would have survived; compare with later replication data.","maturity":"speculative","actor":"regulator","cost":"small","horizonYears":1},{"id":"idea-biomarker-quadruplet-gastric","kind":"idea","name":"Biomarker-directed first-line quadruplets in gastric cancer","aka":[],"tldr":"Stomach cancer now has three add-on biomarkers (HER2, PD-L1, Claudin 18.2) that often overlap. Test whether combining two add-ons beats picking one.","summary":"Gastric cancer now has three first-line add-on biomarkers, HER2, PD-L1 and Claudin 18.2, which sometimes overlap. This idea asks whether tumours that are both CLDN18.2-positive and PD-L1 CPS 5 or higher do better with chemotherapy plus zolbetuximab plus PD-1 blockade than with chemotherapy plus a PD-1 inhibitor alone. The rationale is that the two add-ons act through non-overlapping mechanisms, antibody-dependent cellular cytotoxicity versus T-cell release, and zolbetuximab-induced cell death may increase antigen presentation. Zolbetuximab with nivolumab is under study in ILUSTRO, HERIZON-GEA-01 combined zanidatamab with tislelizumab, and the proposed test is a randomised phase 3 in double-positive patients, at an early clinical stage.","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT03504397: SPOTLIGHT & GLOW","url":"https://clinicaltrials.gov/study/NCT03504397"},{"label":"ClinicalTrials.gov NCT02872116: CheckMate 649","url":"https://clinicaltrials.gov/study/NCT02872116"}],"tags":[],"related":[],"cancers":["gastric"],"sections":[],"technologies":[],"targets":["cldn18-2","pd1","her2"],"drugs":["zolbetuximab","nivolumab","zanidatamab","tislelizumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["spotlight-glow","checkmate-649","herizon-gea-01"],"people":[],"bottlenecks":[],"keyPapers":["paper-yarden-sliwkowski-erbb-network-nrmcb-2001"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"In CLDN18.2-positive, PD-L1 CPS ≥5 tumours, chemotherapy + zolbetuximab + PD-1 blockade improves OS over chemotherapy + PD-1 alone without prohibitive toxicity.","rationale":"Non-overlapping mechanisms (ADCC vs T-cell release); zolbetuximab-induced cell death may increase antigen presentation.","test":"Randomised phase 3 in double-positive patients; OS primary; ctDNA and CLDN18.2 heterogeneity as stratifiers.","maturity":"early-clinical"},{"id":"idea-moon-cardioprotection-by-default","kind":"idea","name":"Biomarker-guided cardioprotection for everyone on cardiotoxic cancer therapy","aka":[],"tldr":"Anthracyclines, HER2 drugs and some newer agents can damage the heart. Monitor with blood tests and scans and start cheap heart-protective drugs early in those at risk.","summary":"Cardio-oncology has grown as a specialty but access is patchy and protective strategies (dexrazoxane, statins, ACE inhibitors, beta-blockers, SGLT2 inhibitors) have mostly small or mixed trials. The proposal is a unified, algorithmic programme: baseline risk score, troponin and strain imaging surveillance at defined points, protocolised initiation of protective therapy on early signals, and a linked registry, tested in a pragmatic randomised trial across anthracycline, HER2 and immune checkpoint regimens.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Toxicity and quality of life are undervalued): Di Maio et al., Symptomatic toxicities experienced during anticancer treatment: agreement between patient and physician reporting (JCO 2015)","url":"https://doi.org/10.1200/JCO.2014.57.9334"}],"tags":[],"related":[],"cancers":["breast-her2-positive","dlbcl"],"sections":[],"technologies":["cardio-oncology"],"targets":[],"drugs":["trastuzumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol","b-survivorship"],"keyPapers":["paper-di-maio-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Biomarker-guided cardioprotection halves the incidence of cancer therapy-related cardiac dysfunction at two years and reduces treatment interruptions for cardiac reasons.","rationale":"Cardiac injury is detectable before it is symptomatic and several inexpensive drugs plausibly protect; the field lacks a standardised, tested pathway rather than candidate interventions.","test":"Pragmatic multi-centre trial randomising centres to the algorithmic programme versus usual care with cardiac dysfunction and oncology dose delivery as co-primary endpoints.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":4},{"id":"idea-adjuvant-selection-rcc","kind":"idea","name":"Biomarker-selected adjuvant therapy in RCC (ctDNA, CAIX PET, gene signatures)","aka":[],"tldr":"Adjuvant immunotherapy after kidney cancer surgery is given to everyone at high pathological risk although most would never relapse, so a year of toxicity is spread across the whole group to help a minority. A biomarker such as CAIX PET or kidney-specific tumour DNA could pick out the few who need it.","summary":"Adjuvant pembrolizumab in KEYNOTE-564, and pembrolizumab with belzutifan in LITESPARK-022, are given to everyone at high pathological risk after nephrectomy, although most would never relapse. This idea proposes selecting patients with a biomarker instead: because renal cell carcinoma sheds little ctDNA, candidates include CAIX PET with 89Zr-girentuximab, kidney-specific ctDNA or methylation assays, and transcriptomic signatures such as ClearCode34. The rationale is that the number needed to treat is high, a year of PD-1 blockade plus HIF-2alpha inhibition carries real toxicity, and IMvigor011 set a precedent in bladder cancer. The proposed test is a biomarker-stratified adjuvant trial with a surveillance arm and a CAIX PET substudy, at an early clinical stage.","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT03142334: KEYNOTE-564","url":"https://clinicaltrials.gov/study/NCT03142334"},{"label":"ClinicalTrials.gov NCT05239728: LITESPARK-022","url":"https://clinicaltrials.gov/study/NCT05239728"}],"tags":[],"related":[],"cancers":["rcc"],"sections":[],"technologies":["caix-pet","mrd-testing"],"targets":[],"drugs":["pembrolizumab","belzutifan"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["keynote-564","litespark-022","imvigor011"],"people":[],"bottlenecks":[],"keyPapers":["paper-keynote-564-nejm-2021"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A post-nephrectomy residual-disease or high-risk signature can identify a subgroup with ≥30% two-year relapse risk in whom adjuvant pembrolizumab ± belzutifan gives an absolute DFS gain of ≥15%, while sparing low-signature patients.","rationale":"Number needed to treat in KEYNOTE-564 is high; toxicity of a year of IO plus HIF-2α inhibition is not trivial; precedent in IMvigor011 for ctDNA-guided adjuvant IO in bladder cancer.","test":"Biomarker-stratified adjuvant trial with a surveillance arm for low-risk-signature patients; CAIX PET substudy.","maturity":"early-clinical"},{"id":"idea-bio1-outlier-lesion-biopsy","kind":"idea","name":"Biopsy the one lesion that is growing while the others shrink","aka":[],"tldr":"When a scan shows most tumours shrinking but one growing, that odd lesion holds the escape mechanism. Sampling it, and treating it locally, should be routine.","summary":"Mixed responses are common on targeted therapy and immunotherapy, yet the discordant lesion is rarely biopsied and the systemic drug is often abandoned. The proposal is a protocolised pathway: automated lesion-level response tracking on CT, biopsy of the outlier, targeted sequencing, and continuation of systemic therapy with local ablation or SBRT to the outlier lesion.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Tumour heterogeneity and clonal evolution): Gerlinger et al., Intratumor heterogeneity and branched evolution (NEJM 2012)","url":"https://doi.org/10.1056/NEJMoa1113205"}],"tags":[],"related":[],"cancers":["nsclc","melanoma"],"sections":[],"technologies":["sbrt","cgp","ct"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["recist","oligometastatic"],"trials":[],"people":[],"bottlenecks":["b-tumor-heterogeneity","b-resistance"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Outlier-lesion biopsy identifies a distinct resistance mechanism in over half of mixed responders, and continuing systemic therapy plus local treatment yields longer time to next systemic line than switching drugs.","rationale":"Oligoprogression management with local therapy is already practised in EGFR and ALK lung cancer; adding the biopsy converts each case into a resistance mechanism datum and prevents premature drug switches.","test":"Single-arm study of 100 mixed responders across tumour types with paired outlier and responding-lesion sequencing; endpoints are mechanism discordance rate and time to next systemic therapy versus matched historical controls.","maturity":"early-clinical","actor":"clinic","cost":"small","horizonYears":2},{"id":"idea-reg-biosimilar-first-default-switching","kind":"idea","name":"Biosimilar-first defaults and payment parity in every cancer day unit","aka":[],"tldr":"Cheaper copies of biological cancer drugs exist but are used far less in some countries than others. Making them the default choice saves billions with no loss of benefit.","summary":"NHS England moved most patients to trastuzumab and rituximab biosimilars within a year of launch through commissioning defaults and shared savings; US uptake was slower because reimbursement incentives favoured the originator. The proposal is a bundle of implementation measures for every payer: prescribing systems default to the lowest-cost interchangeable biologic, payment parity so clinics do not lose revenue by switching, pharmacist-led switching protocols with patient information, and public reporting of biosimilar share by centre.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Prices and value): Prasad, De Jesús & Mailankody, The high price of anticancer drugs: origins, implications, barriers, solutions (Nat Rev Clin Oncol 2017)","url":"https://doi.org/10.1038/nrclinonc.2017.31"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["monoclonal-antibody"],"targets":[],"drugs":["trastuzumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-drug-pricing"],"keyPapers":["paper-prasad-nat-rev-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"The bundle raises biosimilar share for oncology monoclonals above 80% within 12 months of launch in adopting systems, saving at least 30% of prior spend on those molecules with no change in clinical outcomes.","rationale":"Biosimilar uptake is a behavioural and incentive problem, not a scientific one; where defaults and incentives were aligned, switching was fast and safe.","test":"Compare biosimilar share and spend between health systems adopting the bundle and matched systems that do not, over the first two years of each new oncology biosimilar launch.","maturity":"being-tested-at-scale","actor":"payer","cost":"small","horizonYears":2},{"id":"idea-bio2-myeloid-engager-bispecific","kind":"idea","name":"Bispecific antibodies that engage macrophages instead of T cells","aka":[],"tldr":"Drugs that grab T cells and drag them onto tumours work well in blood cancers. The same trick aimed at tumour-eating cells might work where T cells are absent.","summary":"T-cell engagers require T cells to be present and functional, which fails in T-cell-poor tumours. Myeloid engagers pairing a tumour antigen with CD47 blockade, SIRP-alpha, CD40 or Fc-gamma receptor agonism localise phagocytic activation to tumour tissue, potentially avoiding the anaemia that limited systemic anti-CD47 antibodies.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Cold tumours and the immunosuppressive microenvironment): Haslam & Prasad, Estimation of the percentage of US patients eligible for and responding to checkpoint inhibitors (JAMA Netw Open 2019)","url":"https://doi.org/10.1001/jamanetworkopen.2019.2535"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["bispecific-antibody","car-nk-macrophage"],"targets":["cd47","her2","trop2"],"drugs":["magrolimab"],"companies":[],"institutions":[],"pathways":[],"terms":["fc-effector","cold-vs-hot"],"trials":[],"people":[],"bottlenecks":["b-tme-immunosuppression","b-toxicity-qol"],"keyPapers":["paper-haslam-jama-netw-open"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A tumour-antigen-anchored myeloid engager produces tumour regression in T-cell-poor models and, in humans, increases phagocytic marker expression in tumour biopsies without the haemolytic anaemia seen with systemic CD47 blockade.","rationale":"Systemic CD47 blockade failed on toxicity and on-target effects in red cells, a classic index problem solved by tumour anchoring. Macrophages are abundant in exactly the tumours where T cells are scarce, so the effector cell is already in place.","test":"Preclinical comparison of anchored versus systemic CD47 blockade for haematological toxicity and efficacy, then a phase 1 with biopsy-based phagocytosis pharmacodynamics.","maturity":"preclinical-evidence","actor":"industry","cost":"medium","horizonYears":7},{"id":"idea-bladder-preservation-mibc","kind":"idea","name":"Bladder preservation for MIBC after perioperative EV + pembrolizumab complete response","aka":[],"tldr":"If the ADC-immunotherapy combination erases the tumour in more than half of patients before surgery, some may not need their bladder removed at all.","summary":"pCR 57% in EV-303 and high pCR in EV-304 raise the question that dostarlimab answered in dMMR rectal cancer: can complete responders skip surgery? Trials (e.g., SunRISe-4 arms, MODERN, and investigator-led bladder-sparing studies) are beginning to test cystectomy omission with ctDNA and MRI-guided surveillance.","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT03924895: EV-303 / KEYNOTE-905","url":"https://clinicaltrials.gov/study/NCT03924895"},{"label":"ClinicalTrials.gov NCT04700124: EV-304 / KEYNOTE-B15","url":"https://clinicaltrials.gov/study/NCT04700124"}],"tags":[],"related":[],"cancers":["urothelial"],"sections":[],"technologies":["mrd-testing","mri"],"targets":[],"drugs":["enfortumab-vedotin","pembrolizumab","signatera"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["ev-303","ev-304"],"people":[],"bottlenecks":[],"keyPapers":["paper-pembrolizumab-urothelial-n-engl-j-med-2017","paper-pembrolizumab-urothelial-lancet-oncol-2017","paper-ev-302-nejm-2024"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Patients with clinical complete response (cystoscopy, MRI, ctDNA-negative) after EV + pembrolizumab can defer cystectomy with a 2-year bladder-intact event-free survival above 70%.","rationale":"Cystectomy carries major morbidity; response depth is now high enough that surveillance may be non-inferior for a selected group, as in rectal cancer organ preservation.","test":"Single-arm bladder-sparing trial with strict clinical complete response criteria and salvage cystectomy, compared against EV-303/304 outcomes; ctDNA (Signatera-type) as an eligibility and monitoring tool.","maturity":"early-clinical"},{"id":"idea-fund-lmic-radiotherapy-finance","kind":"idea","name":"Blended finance and a low-cost linac to close the global radiotherapy gap","aka":[],"tldr":"Dozens of countries have no radiotherapy machine at all. Combine long-term finance with a machine designed to be cheap, robust and maintainable where power and engineers are scarce.","summary":"Two linked efforts: a blended-finance facility (development banks, IAEA Rays of Hope, philanthropy) that finances radiotherapy centres including training and maintenance contracts over ten years rather than one-off machine donations; and an open engineering programme (following the CERN and STFC initiative for a linac for challenging environments) for a linear accelerator designed for unstable power, high ambient temperature, remote diagnostics and modular repair, manufactured at a fraction of current cost. The two must go together: machines without finance for staff and service become the idle equipment already common in low-income settings.","asOf":"2026-09-08","links":[{"label":"IAEA Rays of Hope","url":"https://www.iaea.org/services/rays-of-hope"}],"tags":[],"related":["idea-fund-global-cancer-fund","idea-fund-lmic-burden-match"],"cancers":["cervical","head-and-neck","breast-hr-positive"],"sections":[],"technologies":["imrt-igrt","brachytherapy"],"targets":[],"drugs":[],"companies":[],"institutions":["iarc","tata-memorial"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-surgery-radiation-innovation","b-global-access"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"The combined programme raises the number of functioning megavoltage machines per million population in participating countries by at least 50% within six years, with machine uptime above 90%, and reduces cost per course of curative radiotherapy below a defined target.","rationale":"Half of cancer patients in low-income countries who need radiotherapy have no access; the Lancet Oncology Commission on global radiotherapy showed investment is highly cost-effective. Donated machines fail for lack of service; finance models that bundle training and maintenance succeed, as in some IAEA and private-partnership examples.","test":"Finance ten centres under the bundled model and deploy two prototype low-cost linacs, tracking uptime, patients treated and cost per course against conventional installations.","maturity":"early-clinical","actor":"philanthropy","cost":"large","horizonYears":6},{"id":"idea-bio1-epigenetic-persister-blockade","kind":"idea","name":"Block the chemical switch that lets cells hide from treatment","aka":[],"tldr":"Cells that survive treatment do so by changing which genes they use, not their DNA. Drugs that block that change may stop survivors from forming at all.","summary":"The persister state depends on chromatin regulators including KDM5A, LSD1 and BRD4, and pharmacological inhibition of these reduced persister formation in the original studies of drug-tolerant cells. The proposal is to use these inhibitors not as continuous therapy but as short pulses during the induction phase, when the persister state is being established, minimising the toxicity that has limited epigenetic drugs.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Acquired resistance to every therapy): Soria et al., Osimertinib in untreated EGFR-mutated NSCLC (FLAURA, NEJM 2018)","url":"https://doi.org/10.1056/NEJMoa1713137"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["epigenetic-drugs"],"targets":["ezh2"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["resistance"],"trials":[],"people":[],"bottlenecks":["b-resistance"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Short-course epigenetic inhibition during the first weeks of targeted therapy reduces the persister population and extends time to resistance, without the cumulative toxicity of continuous dosing.","rationale":"The persister transition is a time-limited event, so exposure only needs to cover that window; epigenetic drugs have failed largely on chronic tolerability rather than lack of activity.","test":"Preclinical schedule optimisation comparing pulsed versus continuous epigenetic inhibition alongside a targeted agent, with persister quantification by lineage tracing, then a phase 1b pulsed schedule.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":6},{"id":"idea-bio2-complement-c5ar-blockade","kind":"idea","name":"Block the complement signal that recruits tumour-protecting cells","aka":[],"tldr":"An old part of the immune system called complement can be hijacked by tumours to summon protective cells. Drugs that block it already exist for other diseases.","summary":"C5a acting through C5aR1 recruits and polarises suppressive myeloid cells in lung, cervical and pancreatic tumour models, and complement inhibitors are approved for rare haematological and kidney diseases, giving established safety data. Combination with checkpoint blockade showed additive effects in mouse models, and small early-phase trials of anti-C5aR1 with checkpoint inhibitors have begun.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Cold tumours and the immunosuppressive microenvironment): Haslam & Prasad, Estimation of the percentage of US patients eligible for and responding to checkpoint inhibitors (JAMA Netw Open 2019)","url":"https://doi.org/10.1001/jamanetworkopen.2019.2535"}],"tags":[],"related":[],"cancers":["nsclc","pancreatic","cervical"],"sections":[],"technologies":["checkpoint-inhibitor","monoclonal-antibody"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["cold-vs-hot"],"trials":[],"people":[],"bottlenecks":["b-tme-immunosuppression","b-generic-repurposing"],"keyPapers":["paper-haslam-jama-netw-open"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"C5aR1 blockade reduces suppressive myeloid infiltration in human tumours and restores checkpoint response in tumours with high complement activation signatures.","rationale":"Complement is an unusual immunotherapy target because clinical-grade inhibitors already exist for other indications, so repositioning is fast. Complement activation signatures are measurable in tissue and plasma, allowing patient selection from the outset.","test":"Signature-selected phase 1b with paired biopsies measuring myeloid infiltration and complement activation, plus a plasma pharmacodynamic assay to confirm target coverage.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":7},{"id":"idea-bio2-autophagy-block-mrd","kind":"idea","name":"Block the recycling that keeps dormant cells alive","aka":[],"tldr":"Sleeping cancer cells survive by recycling their own contents. An old malaria drug blocks that recycling and is being tested in people with no visible cancer but detectable residual cells.","summary":"Dormant disseminated cells depend on autophagy for survival, and hydroxychloroquine plus mTOR inhibition has been tested in bone-marrow-positive breast cancer survivors in the CLEVER-type design at Johns Hopkins. The concept is attractive because it treats survivors while disease burden is at its minimum, but hydroxychloroquine is a weak, non-specific autophagy inhibitor; a potent selective ULK1 or ATG7 inhibitor would be the real test.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Dormant cells and minimal residual disease): Tie et al., ctDNA analysis guiding adjuvant therapy in stage II colon cancer (NEJM 2022)","url":"https://doi.org/10.1056/NEJMoa2200075"}],"tags":[],"related":[],"cancers":["breast-hr-positive","tnbc"],"sections":[],"technologies":["mrd-testing","liquid-biopsy"],"targets":[],"drugs":["everolimus"],"companies":[],"institutions":["johns-hopkins"],"pathways":[],"terms":["mrd","late-recurrence"],"trials":[],"people":[],"bottlenecks":["b-dormancy-mrd","b-generic-repurposing"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Selective autophagy inhibition clears bone-marrow disseminated tumour cells or converts ctDNA-positive survivors to ctDNA-negative at a materially higher rate than observation.","rationale":"Autophagy dependence is a well-documented feature of quiescent, nutrient-poor cells, and dormancy is the setting where selective vulnerability should be largest. The endpoint is molecular and cheap, so a small trial can give a clear answer.","test":"A randomised phase 2 in ctDNA-positive or marrow-positive survivors comparing selective autophagy inhibition with observation, primary endpoint molecular clearance at 12 months, with serial marrow and plasma sampling.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":5},{"id":"idea-bio1-stromal-resistance-blockade","kind":"idea","name":"Block the survival signals the tumour's neighbours provide","aka":[],"tldr":"Cancer cells can survive a drug because surrounding normal cells feed them growth signals. Blocking those signals could make existing drugs work better and longer.","summary":"Fibroblast- and macrophage-derived factors including HGF, FGFs and neuregulin rescue tumour cells from targeted therapy in co-culture and in vivo, an effect largely invisible in monoculture screens. Environment-mediated resistance argues for combining targeted agents with blockade of the specific rescuing ligand or its receptor, selected by profiling the tumour's own stroma rather than the tumour cells alone.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Acquired resistance to every therapy): Soria et al., Osimertinib in untreated EGFR-mutated NSCLC (FLAURA, NEJM 2018)","url":"https://doi.org/10.1056/NEJMoa1713137"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["single-cell-spatial"],"targets":["met","fap","her3"],"drugs":["patritumab-deruxtecan"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-resistance","b-tme-immunosuppression"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Stroma-directed ligand blockade added to targeted therapy deepens response in tumours whose stroma expresses the rescuing ligand, and stromal ligand expression predicts which patients benefit.","rationale":"The rescue phenomenon was demonstrated systematically in large co-culture screens; the clinical failure of some combination trials may reflect unselected populations rather than a wrong mechanism.","test":"Score stromal ligand expression on baseline biopsies from a completed combination trial to test the predictive hypothesis retrospectively before designing a selected prospective study.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":5},{"id":"idea-prev-ebv-dna-npc-screening-scaleup","kind":"idea","name":"Blood EBV DNA screening for nasopharyngeal cancer across southern China and Southeast Asia","aka":[],"tldr":"Nasopharyngeal cancer is common in southern China and is caused by a virus. A blood test for viral DNA finds it early, and a large study showed better survival. Scale it up.","summary":"Plasma EBV DNA screening detected nasopharyngeal carcinoma at earlier stage with improved progression-free survival in a 20,000-man Hong Kong study. Propose programme rollout in high-incidence regions with two-time-point confirmation, endoscopy for persistent positives, and mortality evaluation via registries.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The hardest cancers are found late): Crosby et al., Early detection of cancer (Science 2022)","url":"https://doi.org/10.1126/science.aay9040"}],"tags":[],"related":[],"cancers":["head-and-neck"],"sections":["early-detection"],"technologies":["liquid-biopsy"],"targets":[],"drugs":[],"companies":[],"institutions":["sysucc"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-early-detection","b-global-access"],"keyPapers":["paper-crosby-science"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Programme screening reduces nasopharyngeal cancer mortality by at least 30% in screened men aged 40-62 in high-incidence regions.","rationale":"A strong single-cancer test with a clear cause; high-incidence regions make positive predictive value acceptable.","test":"Cluster-randomised implementation in Guangdong or Guangxi with registry follow-up.","maturity":"being-tested-at-scale","actor":"policy","cost":"medium","horizonYears":6},{"id":"idea-hcc-blood-surveillance","kind":"idea","name":"Blood-based HCC surveillance to replace six-monthly ultrasound","aka":[],"tldr":"A blood test (methylation, GALAD) that finds liver cancer early in people with cirrhosis, especially those with fatty liver where ultrasound fails.","summary":"The idea is to replace six-monthly ultrasound surveillance for hepatocellular carcinoma in cirrhosis with a blood test, using cell-free DNA methylation panels or the GALAD score that incorporates alpha-fetoprotein. Ultrasound misses much early HCC in obese and steatotic livers, whereas blood is unaffected by body habitus and can be posted, and poor adherence is the biggest failure of current surveillance. The hypothesis is that blood surveillance in fatty-liver cirrhosis detects more early-stage HCC than ultrasound at an acceptable false-positive rate, increasing curative-intent treatment. The test is a randomised or paired-design trial with early-stage detection and curative treatment as endpoints; it addresses the bottleneck that the hardest cancers are found late.","asOf":"2026-09-07","links":[{"label":"Chalasani et al., Validation of a novel multitarget blood test shows high sensitivity to detect early-stage hepatocellular carcinoma (Clinical Gastroenterology and Hepatology 2022)","url":"https://doi.org/10.1016/j.cgh.2021.08.010"}],"tags":[],"related":[],"cancers":["hcc"],"sections":[],"technologies":["hcc-surveillance","mced","methylation-profiling"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["afp"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-chalasani-clin-gastroenterol-hepatol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Six-monthly blood surveillance detects more early-stage HCC than ultrasound in MASLD cirrhosis at acceptable false-positive rates, increasing curative-intent treatment.","rationale":"Blood is unaffected by body habitus and can be mailed; adherence is the biggest failure of current surveillance.","test":"Randomised or paired-design surveillance trial with early-stage detection and curative treatment rate as endpoints.","maturity":"early-clinical"},{"id":"idea-mced-new-onset-diabetes","kind":"idea","name":"Blood-based pancreatic cancer detection in new-onset diabetes","aka":[],"tldr":"Adults who suddenly develop diabetes after 50 have several times the usual risk of pancreatic cancer. Test their blood.","summary":"Adults who develop diabetes after the age of 50 carry a raised risk of harbouring an occult pancreatic ductal adenocarcinoma, and this idea proposes testing their blood rather than waiting for symptoms. Risk-stratified testing with a multi-cancer early detection assay such as Galleri, or a multi-analyte CA 19-9 panel, would be offered to people with a high END-PAC score, with imaging reserved for those who test positive. Because cancer is far more prevalent in this enriched group, the positive predictive value of a blood test rises into a useful range. The test would be a prospective NOD-type cohort with blinded blood testing and three years of cancer ascertainment. At an early clinical stage, it addresses the bottleneck that the hardest cancers are found late.","asOf":"2026-09-06","links":[{"label":"PATHFINDER: the first prospective test of a multi-cancer blood test in people without symptoms (The Lancet 2023)","url":"https://doi.org/10.1016/S0140-6736(23)01700-2"},{"label":"NHS-Galleri: design of the largest randomised trial of a multi-cancer blood test (Cancers 2022)","url":"https://doi.org/10.3390/cancers14194818"}],"tags":[],"related":[],"cancers":["pancreatic"],"sections":[],"technologies":["mced","pancreatic-surveillance"],"targets":[],"drugs":["galleri"],"companies":[],"institutions":[],"pathways":[],"terms":["ppv","ca19-9"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Risk-stratified blood testing (MCED or multi-analyte CA19-9 panel) in high-END-PAC-score new-onset diabetes detects PDAC at resectable stage with acceptable PPV.","rationale":"Enriched prevalence (~1%) raises PPV to a useful range; imaging can be reserved for test-positives.","test":"Prospective cohort (NOD-type) with blinded blood testing and 3-year cancer ascertainment; compare stage distribution with contemporaneous controls.","maturity":"early-clinical"},{"id":"idea-bio2-il1-awakening-blockade","kind":"idea","name":"Blunt the inflammation that wakes sleeping cancer cells","aka":[],"tldr":"Inflammation from infection, injury or surgery can wake dormant cancer cells. Interleukin-1 beta drives that awakening in mouse models of breast cancer, and a cardiovascular trial of the interleukin-1 beta blocker canakinumab saw fewer lung cancers, so blocking it early might keep dormant cells asleep.","summary":"Interleukin-1 beta from the bone marrow niche drives the exit of breast cancer cells from dormancy and metastatic outgrowth in mouse models, and a large cardiovascular trial of canakinumab reported an unexpected reduction in lung cancer incidence and mortality. Later lung cancer treatment trials of canakinumab in advanced disease were negative, which is consistent with awakening being an early, not late, event.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Dormant cells and minimal residual disease): Tie et al., ctDNA analysis guiding adjuvant therapy in stage II colon cancer (NEJM 2022)","url":"https://doi.org/10.1056/NEJMoa2200075"}],"tags":[],"related":[],"cancers":["breast-hr-positive","nsclc"],"sections":[],"technologies":["mrd-testing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["mrd","late-recurrence"],"trials":[],"people":[],"bottlenecks":["b-dormancy-mrd","b-metastasis-biology"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Interleukin-1 beta blockade in high-risk survivors reduces distant relapse rate, whereas the same drug has no effect in established metastatic disease.","rationale":"Setting-dependence is the crux: an awakening inhibitor cannot shrink a tumour that is already growing. Testing prevention rather than treatment aligns the mechanism with the endpoint, and the CANTOS incidence signal is a human-level hint that the axis matters.","test":"A randomised trial in ctDNA-positive or clinically high-risk resected breast or lung cancer with relapse-free survival and ctDNA clearance as co-primary endpoints, powered for a modest effect and sized off the CANTOS incidence data.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":7},{"id":"idea-tr1-bayesian-borrowing-smaller-controls","kind":"idea","name":"Borrow from past control arms to shrink the control group in phase 3","aka":[],"tldr":"When the standard treatment has been given to thousands of similar patients in earlier trials, a new trial could randomise fewer people to it and lean on that history, as long as the old data still matches.","summary":"Hybrid control designs use Bayesian dynamic borrowing (power priors, meta-analytic-predictive priors, commensurate priors) from curated historical control arms and real-world cohorts to reduce concurrent control allocation to 1:2 or 1:3 while retaining randomisation. Borrowing is down-weighted automatically when the concurrent controls diverge from history. The FDA Complex Innovative Design programme has reviewed such designs; oncology uptake is limited.","asOf":"2026-09-08","links":[{"label":"FDA Complex Innovative Trial Design meeting programme","url":"https://www.fda.gov/drugs/development-resources/complex-innovative-trial-design-meeting-program"}],"tags":[],"related":[],"cancers":["nsclc","colorectal"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["hazard-ratio","standard-of-care"],"trials":[],"people":[],"bottlenecks":["b-trial-design","b-trial-enrolment"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Hybrid-control phase 3 trials in well-characterised indications will reach the same decision as a conventional 1:1 trial with 25-40 percent fewer control patients and shorter accrual, and the borrowing weight will correctly fall when historical drift exists.","rationale":"Control-arm outcomes in first-line NSCLC, metastatic breast and CRC are stable across recent trials with the same regimen; requiring 400 fresh control patients every time is a cost paid by patients as well as sponsors.","test":"Re-analyse three completed phase 3 trials as if run with dynamic borrowing from pre-existing control data; confirm identical conclusions. Then run one prospective hybrid trial under the CID programme.","maturity":"early-clinical","actor":"industry","cost":"medium","horizonYears":3},{"id":"idea-tr2-replication-bounties","kind":"idea","name":"Bounties for documented failed replications of high-impact findings","aka":[],"tldr":"Pay a fixed reward to any lab that pre-registers and carefully repeats a heavily cited preclinical cancer finding, whatever the outcome, with a bonus for the first documented non-replication that passes methodological review. Today that work is unpaid and unpublished.","summary":"Security research uses bug bounties to reward finding flaws. A replication bounty programme would list high-impact preclinical oncology findings (selected by citations and translational stage), pay a fixed sum for a pre-registered, adequately powered replication attempt regardless of outcome, and a bonus for the first documented non-replication that passes methodological review. Results are published in a registry.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Preclinical results do not reproduce): Errington et al., Investigating the replicability of preclinical cancer biology (eLife 2021)","url":"https://doi.org/10.7554/eLife.71601"}],"tags":[],"related":["idea-tr2-replication-set-aside","idea-tr2-preclinical-negative-registry"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-reproducibility","b-negative-results"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"The programme will produce at least 50 pre-registered replications per year at a cost per replication under a tenth of a standard grant, and at least a third of targeted findings will fail to replicate.","rationale":"Replication attempts already happen informally in labs and industry; the bounty converts private knowledge into public record at low cost.","test":"Fund 50 bounties in year one; measure uptake, methodological quality of submissions and publication of results.","maturity":"speculative","actor":"philanthropy","cost":"small","horizonYears":1},{"id":"idea-atc-triplet-io","kind":"idea","name":"BRAF/MEK plus PD-1 blockade as standard for BRAF-mutant anaplastic thyroid cancer","aka":[],"tldr":"Add immunotherapy to the two targeted pills in the most aggressive thyroid cancer, because the combination has produced multi-year survivors in early series.","summary":"The idea is to make dabrafenib and trametinib plus pembrolizumab the standard first-line treatment for BRAF V600E-mutant anaplastic thyroid cancer. Anaplastic thyroid cancer is immunologically hot relative to differentiated cancers, with high PD-L1 expression and mutational burden, and targeted therapy induces rapid antigen release that checkpoint blockade can exploit. MD Anderson series of the triplet report multi-year survivors and longer overall survival than the doublet, building on the anaplastic cohort of the ROAR trial. The hypothesis is that adding pembrolizumab extends overall survival; given the rarity of the disease, the test is an international randomised phase 2 of doublet versus triplet with survival at one year as primary endpoint.","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT02034110: ROAR (anaplastic thyroid cancer cohort)","url":"https://clinicaltrials.gov/study/NCT02034110"}],"tags":[],"related":[],"cancers":["thyroid"],"sections":[],"technologies":[],"targets":["braf","pd1"],"drugs":["dabrafenib-trametinib","pembrolizumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["roar-atc"],"people":[],"bottlenecks":[],"keyPapers":["paper-braf-thyroid-n-engl-j-med-2015","paper-braf-thyroid-endocr-relat-cancer-2005","paper-braf-thyroid-endocr-rev-2007"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Adding pembrolizumab to dabrafenib-trametinib extends OS in BRAF V600E ATC.","rationale":"Targeted therapy induces rapid immunogenic response and antigen release; ATC is immunologically hot relative to differentiated cancers.","test":"International randomised phase 2 (doublet vs triplet) given rarity, with OS at 12 months as primary endpoint.","maturity":"early-clinical"},{"id":"idea-tr1-brain-mets-default-included","kind":"idea","name":"Brain metastases included by default in every solid-tumour trial","aka":[],"tldr":"Up to a fifth of people with advanced solid tumours have cancer in the brain and are usually barred from trials. Letting in those whose brain disease is treated, stable or symptom-free would widen trials and tell us whether drugs work in the brain.","summary":"Protocols would include patients with treated and stable brain metastases, and asymptomatic untreated metastases below a size threshold, with a pre-specified intracranial response assessment (RANO-BM) as a secondary endpoint. Exclusion would be allowed only for agents with a documented neurotoxicity signal or where the sponsor pre-registers a separate CNS cohort. The FDA brain metastases eligibility guidance supports this but uptake remains partial.","asOf":"2026-09-08","links":[{"label":"FDA: Cancer Clinical Trial Eligibility Criteria: Brain Metastases","url":"https://www.fda.gov/regulatory-information/search-fda-guidance-documents/cancer-clinical-trial-eligibility-criteria-brain-metastases"}],"tags":[],"related":[],"cancers":["nsclc","breast-her2-positive","melanoma"],"sections":[],"technologies":["mri"],"targets":[],"drugs":["osimertinib","lorlatinib","tucatinib","trastuzumab-deruxtecan"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-enrolment","b-brain-delivery"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Trials including stable and asymptomatic brain metastases will enrol faster, and the intracranial efficacy data generated will change labelling or guidelines for at least a quarter of new agents in lung, breast and melanoma within five years.","rationale":"Osimertinib, lorlatinib, tucatinib and trastuzumab deruxtecan changed practice for brain metastases only because trials permitted such patients. Excluding them creates an evidence vacuum for exactly the population with the greatest unmet need.","test":"Compare enrolment rate and CNS-relevant label changes between new registrational trials that adopt default inclusion versus those that do not, using ClinicalTrials.gov records over a three-year window.","maturity":"early-clinical","actor":"regulator","cost":"small","horizonYears":2},{"id":"idea-bio2-net-blockade-perioperative","kind":"idea","name":"Break the neutrophil DNA nets that catch tumour cells after surgery","aka":[],"tldr":"Surgery makes some immune cells throw out sticky DNA webs that trap travelling cancer cells and help them settle. Dissolving those webs during the operation might prevent some relapses.","summary":"Neutrophil extracellular traps capture circulating tumour cells and promote liver and lung seeding in multiple mouse models, and trap markers rise sharply after large cancer operations. DNase I is an approved inhaled drug and PAD4 inhibitors are in development, so a perioperative net-dissolving window trial is quick and cheap to run.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Metastasis is understood least and studied last): Dillekås et al., Are 90% of deaths from cancer caused by metastases? (Cancer Medicine 2019)","url":"https://doi.org/10.1002/cam4.2474"}],"tags":[],"related":[],"cancers":["colorectal","pancreatic"],"sections":[],"technologies":["liquid-biopsy","mrd-testing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["ctdna"],"trials":[],"people":["erik-sahai"],"bottlenecks":["b-metastasis-biology","b-dormancy-mrd"],"keyPapers":["paper-dillekas-cancer-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Perioperative net degradation with DNase or a PAD4 inhibitor reduces postoperative ctDNA positivity at four weeks by a third after colorectal or pancreatic resection, and lowers two-year distant relapse.","rationale":"The postoperative period is a brief, defined window of raised metastatic risk, and neutrophil traps are one of the few molecular explanations for it that already has drugs in hand and measurable pharmacodynamics.","test":"A 120-patient randomised window trial in colorectal liver resection or pancreatic resection with day-28 ctDNA as primary endpoint and trap markers such as citrullinated histone H3 as pharmacodynamic readouts.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":6},{"id":"idea-bio1-condensate-disruptors","kind":"idea","name":"Break up the liquid droplets where oncogenic transcription happens","aka":[],"tldr":"Some cancer-driving proteins gather into droplet-like blobs inside the nucleus to switch genes on. Drugs that dissolve those blobs might switch the cancer programme off.","summary":"Transcriptional condensates concentrate MYC, fusion oncoproteins, mediator complex and RNA polymerase at super-enhancers. Certain drugs, including some antineoplastics, concentrate selectively in condensates, and condensate-modulating chemotypes have been reported. A dedicated screen using condensate-specific reporters (optoDroplet or in vitro reconstitution with labelled scaffolds) could identify compounds that selectively dissolve oncogenic condensates while sparing normal ones.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The undruggable drivers): Dang et al., Drugging the 'undruggable' cancer targets (Nature Reviews Cancer 2017)","url":"https://doi.org/10.1038/nrc.2017.36"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["epigenetic-drugs"],"targets":[],"drugs":[],"companies":[],"institutions":["dana-farber","broad-institute"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-undruggable-targets"],"keyPapers":["paper-dang-nat-rev-cancer"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Compounds that dissolve oncoprotein condensates suppress super-enhancer-driven transcription and kill condensate-dependent tumour cells at concentrations that do not affect housekeeping transcription.","rationale":"Condensate biology is a general mechanism for transcription factors that lack pockets, and drug partitioning into condensates has been shown to affect potency, so the physics is at least addressable.","test":"Reconstituted condensate screens with orthogonal cellular validation in an EWS-FLI1 and a MYC-amplified model, with transcriptomic evidence of selective super-enhancer target loss.","maturity":"speculative","actor":"research","cost":"medium","horizonYears":9},{"id":"idea-cost-travel-teleoncology","kind":"idea","name":"Bring the oncologist to the local clinic by video and the drug to the local pharmacy","aka":[],"tldr":"Travel and time off work are among the biggest costs families face; if consultations happen by video, blood tests locally and oral drugs by mail, most routine visits need no journey at all.","summary":"Rural patients travel hours for a fifteen-minute review. Tele-oncology models (Australia's Townsville network, the US Veterans Health Administration) pair a remote oncologist with a local nurse or general practitioner, local laboratory draws and mail-order or local dispensing of oral drugs; infusions are given at the nearest capable site. Decentralised trial designs use the same infrastructure. Payment parity for video visits, which many payers made permanent after 2020, removes the main barrier.","asOf":"2026-09-10","links":[{"label":"Medicare.gov: Telehealth","url":"https://www.medicare.gov/coverage/telehealth"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["ai-trial-matching"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["financial-toxicity"],"trials":[],"people":[],"bottlenecks":["b-care-fragmentation","b-global-access","b-trial-enrolment"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A hub-and-spoke tele-oncology model will cut patient travel distance for routine care by more than half and reduce out-of-pocket travel and lost-wage cost by a comparable share, with equal guideline concordance and survival.","rationale":"Published tele-oncology programmes report equivalent outcomes and high satisfaction; the saving falls to patients, who are otherwise invisible in cost accounting.","test":"Regional implementation with patient-reported travel time and cost, visit completion, time to treatment and survival compared with the pre-implementation cohort.","maturity":"being-tested-at-scale","actor":"clinic","cost":"medium","horizonYears":3},{"id":"idea-data-consent-in-the-pathway","kind":"idea","name":"Broad research consent as a routine step of the cancer pathway","aka":[],"tldr":"Every newly diagnosed patient would be asked, as part of standard care, whether their data and leftover tissue can be used for research, so researchers never have to go back and ask.","summary":"Cancer centres such as Memorial Sloan Kettering and the Princess Margaret already consent a majority of patients to institutional research protocols at first visit. The proposal is to make this a nationally standardised pathway step with a common consent text and a shared flag in the record, so that data from consented patients can be pooled across centres without re-consent. Ethics committees would recognise the common consent as sufficient for defined categories of research.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Data silos): AACR Project GENIE","url":"https://www.aacr.org/professionals/research/aacr-project-genie/"}],"tags":[],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["mskcc","princess-margaret"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-data-silos","b-trial-enrolment"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A common pathway consent recognised by all ethics committees in a country will make more than 80 percent of new patients research-ready at diagnosis and remove re-consent as a barrier in more than 90 percent of retrospective studies.","rationale":"Where institutions have made consent routine, enrolment rates above 70 percent are typical; the problem is that each institution's consent is unique and not recognised elsewhere.","test":"Agree a common consent text among five centres and one national ethics body; measure the share of patients research-ready and the number of multi-centre studies that proceed without re-consent over two years.","maturity":"early-clinical","actor":"clinic","cost":"small","horizonYears":2},{"id":"idea-btk-degrader-frontline","kind":"idea","name":"BTK degraders to pre-empt resistance in frontline CLL","aka":[],"tldr":"If destroying BTK works when every inhibitor has failed, using it first might stop resistance from ever emerging.","summary":"The idea is to use a BTK degrader such as BGB-16673 with a BCL-2 inhibitor such as sonrotoclax as a 12-month fixed-duration frontline regimen for chronic lymphocytic leukaemia, pre-empting the acquired-resistance bottleneck. Degradation removes both kinase and scaffold functions and is not defeated by the C481, T474 or L528 mutations that arise under inhibitor pressure; BGB-16673 works in most heavily pretreated, mutation-bearing patients. The hypothesis is deeper undetectable MRD, longer treatment-free survival and fewer resistance mutations than a covalent BTK inhibitor with venetoclax. The test is a phase 2 of BGB-16673 with sonrotoclax in untreated patients, then a randomised comparison against acalabrutinib-venetoclax; CaDAnCe-304 already tests the degrader in relapse.","asOf":"2026-09-07","links":[{"label":"Montoya et al., Kinase-impaired BTK mutations are susceptible to the clinical-stage BTK and IKZF1/3 degrader NX-2127 (Science 2024)","url":"https://doi.org/10.1126/science.adi5798"}],"tags":[],"related":[],"cancers":["cll"],"sections":[],"technologies":["protac-degrader"],"targets":["btk","bcl2"],"drugs":["bgb-16673","sonrotoclax","acalabrutinib","venetoclax"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["cadance-304"],"people":[],"bottlenecks":[],"keyPapers":["paper-montoya-science","paper-acalabrutinib-cll-n-engl-j-med-2016","paper-bcl-2-cll-nat-rev-drug-discov-2017","paper-acalabrutinib-cll-j-clin-oncol-2021"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A BTK degrader plus a BCL-2 inhibitor for 12 months produces higher uMRD and longer treatment-free survival than covalent BTKi + venetoclax, with fewer BTK resistance mutations at relapse.","rationale":"Degradation removes both kinase and scaffold functions and is not defeated by C481, T474, or L528 mutations that arise under inhibitor pressure.","test":"Phase 2 doublet (BGB-16673 + sonrotoclax) in treatment-naive CLL with uMRD at month 15 as the primary endpoint, then randomised comparison with acalabrutinib-venetoclax.","maturity":"early-clinical"},{"id":"idea-bio2-blood-csf-barrier-model","kind":"idea","name":"Build a human model of the barrier that guards the brain fluid","aka":[],"tldr":"Drugs that reach brain tissue may still fail to reach the fluid where cancer spreads along the linings. A lab model of that second barrier would let us screen for drugs that cross it.","summary":"Leptomeningeal disease is governed by the blood-cerebrospinal fluid barrier at the choroid plexus, which differs from the blood-brain barrier in transporters and tight junction composition. Stem-cell-derived choroid plexus organoids that produce cerebrospinal fluid-like secretion have been reported, giving a human in vitro system for screening cerebrospinal fluid penetration and for studying how tumour cells survive in that nutrient-poor compartment.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The brain: barrier and sanctuary): Stupp et al., Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma (NEJM 2005)","url":"https://doi.org/10.1056/NEJMoa043330"}],"tags":[],"related":[],"cancers":["breast-her2-positive","nsclc","melanoma"],"sections":[],"technologies":["organoids"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["blood-brain-barrier"],"trials":[],"people":[],"bottlenecks":["b-brain-delivery","b-preclinical-models"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Choroid plexus organoid permeability ranks drugs concordantly with measured human cerebrospinal fluid-to-plasma ratios, making it a usable screening assay for leptomeningeal indications.","rationale":"Leptomeningeal metastasis is rarely survived beyond a few months and is increasingly common as systemic control improves, yet drug selection for it is guesswork. A quantitative human assay for the correct barrier is a prerequisite for rational selection.","test":"Benchmark organoid permeability against 20 drugs with published human cerebrospinal fluid-to-plasma ratios; report rank correlation and cost per compound.","maturity":"preclinical-evidence","actor":"engineering","cost":"medium","horizonYears":6},{"id":"idea-bio1-metastatic-niche-models","kind":"idea","name":"Build laboratory models of the organs cancer spreads to","aka":[],"tldr":"Cancer usually kills by spreading to bone, liver, lung or brain. Almost all laboratory models grow tumours under the skin instead, where the surroundings are nothing like those organs.","summary":"Subcutaneous xenografts remain the default despite being the least relevant site. Engineered bone marrow niches, liver-on-chip with resident macrophages, and perfused lung and brain models can be seeded with patient tumour cells to study colonisation, dormancy and organ-specific drug response. Organ-specific microenvironments determine both seeding and treatment sensitivity.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Lab models that fail to predict what happens in patients): Wong, Siah & Lo, Estimation of clinical trial success rates (Biostatistics 2019)","url":"https://doi.org/10.1093/biostatistics/kxx069"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["organoids","pdx-models"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["oligometastatic"],"trials":[],"people":[],"bottlenecks":["b-preclinical-models","b-metastasis-biology"],"keyPapers":["paper-wong-biostatistics"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Drug sensitivity of the same tumour cells differs substantially between organ-mimicking niches, and niche-specific results predict site-specific clinical response better than subcutaneous models.","rationale":"Clinically, responses differ by metastatic site (for example liver metastases predict poor immunotherapy benefit), which no subcutaneous model can represent.","test":"Test three agents against matched tumour cells in bone, liver and lung niche models and compare with site-specific response data from clinical imaging cohorts.","maturity":"speculative","actor":"engineering","cost":"medium","horizonYears":5},{"id":"idea-prev-prs-ancestry-portability-standard","kind":"idea","name":"Build polygenic scores that work in every ancestry before deploying any","aka":[],"tldr":"Genetic risk scores were built mostly on Europeans and work worse in others. Funding non-European cohorts and setting a portability standard would prevent screening that widens inequality.","summary":"Polygenic risk scores were built mostly on Europeans and work worse in others, so this idea funds diverse cohorts and sets a portability standard requiring comparable PRS discrimination across ancestries before any score is used in screening. Accuracy drops substantially in African and South Asian ancestry, the gap is a training-data problem, and deployment without standards locks in inequity. The aim is to close the performance gap for breast, prostate and colorectal PRS within five years. The test benchmarks scores annually against a held-out multi-ancestry cohort. At early-clinical maturity it addresses the bottlenecks Inherited risk is mostly unidentified and Trials do not represent the people who get cancer.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Inherited risk is mostly unidentified): Childers et al., National estimates of genetic testing in women with breast or ovarian cancer (JCO 2017)","url":"https://doi.org/10.1200/JCO.2017.73.6314"}],"tags":[],"related":[],"cancers":[],"sections":["prevention"],"technologies":["germline-testing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-hereditary-risk","b-trial-diversity"],"keyPapers":["paper-childers-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Multi-ancestry training and standards reduce the performance gap for breast, prostate and colorectal PRS to under 20% within five years.","rationale":"The portability gap is a training-data problem; deployment without standards locks in inequity.","test":"Benchmark PRS annually against a held-out multi-ancestry cohort.","maturity":"early-clinical","actor":"research","cost":"large","horizonYears":5},{"id":"idea-reg-yb176-enrichment-capacity","kind":"idea","name":"Build Western ytterbium-176 enrichment so lutetium-177 has more than one supplier","aka":[],"tldr":"The lutetium used in approved prostate and neuroendocrine cancer treatments is made from an enriched metal that comes mostly from Russia. Making it elsewhere would secure supply.","summary":"No-carrier-added lutetium-177 is produced by irradiating enriched ytterbium-176, most of which has historically come from Russian electromagnetic separators. Demand is rising steeply with Pluvicto, Lutathera and pipeline radioligands. Several companies (ASP Isotopes, ITM, SHINE and others) are developing laser or centrifuge enrichment in North America and Europe. The proposal is an advance market commitment by health systems and manufacturers to buy a guaranteed volume of Western-enriched ytterbium-176 at a floor price for ten years, with a strategic buffer stock, mirroring how vaccine advance commitments created capacity.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Manufacturing cost and time for living and radioactive medicines): Hernandez, Prasad & Gellad, Total costs of chimeric antigen receptor T-cell immunotherapy (JAMA Oncology 2018)","url":"https://doi.org/10.1001/jamaoncol.2018.0977"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["radioligand-therapy"],"targets":[],"drugs":["pluvicto","lutathera"],"companies":["itm","novartis"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-manufacturing-cell-therapy","b-global-access"],"keyPapers":["paper-hernandez-jama-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Advance commitments bring at least two non-Russian enrichment facilities to commercial output within four years, supplying more than half of global ytterbium-176 demand, and lutetium-177 supply interruptions to clinics fall to zero.","rationale":"Enrichment is a capital-intensive, low-margin step whose investors need demand certainty; the clinical demand is now visible and growing, and geopolitical risk to a single-source supply chain is evident.","test":"Model demand to 2035 with the major radioligand producers, structure a joint offtake agreement, and measure delivered enrichment capacity and supply-interruption reports over five years.","maturity":"early-clinical","actor":"industry","cost":"large","horizonYears":4},{"id":"idea-acc-episode-payment-tied-to-concordance","kind":"idea","name":"Bundled episode payments for cancer care with bonuses for guideline concordance","aka":[],"tldr":"Pay hospitals a single amount for a whole course of cancer treatment, with extra for following the evidence, rather than paying per visit and per drug, which rewards fragmentation.","summary":"The US Oncology Care Model and its successor tested episode-based payment for chemotherapy episodes with quality measures; results on cost were mixed, but process measures improved. A design that ties a larger share of payment to guideline concordance, supportive care access, and avoidance of low-value end-of-life chemotherapy, while adjusting for case mix, could align incentives with coordination. This is a payer experiment, and needs careful attention to unintended effects.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Fragmented care and guideline gaps): Hanna et al., Mortality due to cancer treatment delay: systematic review and meta-analysis (BMJ 2020)","url":"https://doi.org/10.1136/bmj.m4087"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-care-fragmentation","b-incentive-misalignment","b-drug-pricing"],"keyPapers":["paper-hanna-bmj"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Episode payment with concordance bonuses will improve guideline-concordant care and reduce emergency visits and end-of-life chemotherapy without increasing total cost per episode.","rationale":"Fee-for-service rewards volume and fragmentation; bundles create a single accountable entity for the episode, which is the precondition for coordination.","test":"A randomised payer pilot across practices with concordance, utilisation, patient experience, and cost as endpoints, evaluated independently.","maturity":"being-tested-at-scale","actor":"payer","cost":"large","horizonYears":5},{"id":"idea-fund-lmic-burden-match","kind":"idea","name":"Burden-matched funding for trials led in low- and middle-income countries","aka":[],"tldr":"Seven in ten cancer deaths are in poorer countries, yet almost all trials happen in rich ones. Funders would commit a share of money for trials designed and led where the burden is.","summary":"The largest cancer research funders commit a fixed fraction (say 15%) of their trials budget to studies whose principal investigator and majority of sites are in low- and middle-income countries, targeting cancers and questions that matter there: cervical cancer treatment with limited radiotherapy, oesophageal squamous cell carcinoma, hepatocellular carcinoma from hepatitis B, hypofractionation and shorter regimens, low-cost generics. Precedents include Tata Memorial's trials that changed global practice on low-dose immunotherapy and neoadjuvant chemotherapy in head and neck cancer at a fraction of Western trial costs.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Funding follows fashion, not burden): Carter & Nguyen, A comparison of cancer burden and research spending (BMC Cancer 2012)","url":"https://doi.org/10.1186/1471-2407-12-526"}],"tags":[],"related":["idea-fund-global-cancer-fund","idea-fund-lmic-radiotherapy-finance"],"cancers":["cervical","esophageal","hcc","head-and-neck"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["tata-memorial","einstein-sao-paulo","sysucc"],"pathways":[],"terms":[],"trials":[],"people":["badwe-rajendra","gupta-sudeep","barrios-carlos"],"bottlenecks":["b-funding-allocation","b-global-access","b-trial-diversity"],"keyPapers":["paper-sun-bmc-cancer"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A burden-matched commitment produces at least ten practice-changing phase 3 results relevant to LMIC settings within a decade at a per-patient cost under a third of comparable high-income trials, and doubles the LMIC share of registered interventional oncology trials.","rationale":"Trials in India, Brazil and China have shown that large, pragmatic, low-cost phase 3s are feasible and change guidelines; the limiting factor is core funding for trial units rather than science. Results generalise upward more often than down: hypofractionation and de-escalation findings from LMIC trials have been adopted in rich countries.","test":"Two funders pool a pilot fund of tens of millions, award competitively to LMIC-led trial units, and audit after five years for trials completed, guideline citations and cost per patient compared with the funders' other trials.","maturity":"speculative","actor":"philanthropy","cost":"large","horizonYears":6},{"id":"idea-fund-burden-weighted-portfolio","kind":"idea","name":"Burden-weighted portfolio targets for every major cancer funder","aka":[],"tldr":"Funders would publish how their spending compares with deaths and years of life lost per cancer, and commit to shift a fixed share of money each year towards the biggest gaps.","summary":"A burden-weighted formula sets a target share for each cancer type and each stage of the pipeline (prevention, detection, metastasis, delivery) using disability-adjusted life years and deaths from GLOBOCAN and the Global Burden of Disease study, adjusted by a tractability discount. Funders publish actual versus target and are held to a rebalancing rule of, for example, moving 10% of the discretionary portfolio per year towards under-funded areas. Analyses of NCI and UK spending have repeatedly shown lung, pancreatic, oesophageal, liver and stomach cancers receive far less per death than breast, leukaemia and prostate.","asOf":"2026-09-08","links":[{"label":"GLOBOCAN (IARC Global Cancer Observatory)","url":"https://gco.iarc.fr/"},{"label":"Global Burden of Disease","url":"https://www.healthdata.org/research-analysis/gbd"},{"label":"International Cancer Research Partnership","url":"https://www.icrpartnership.org/"}],"tags":[],"related":["idea-fund-dollars-per-death-dashboard","idea-fund-cross-funder-portfolio-registry"],"cancers":["pancreatic","esophageal","hcc","gastric","nsclc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["nci","cruk","iarc"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-funding-allocation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"If the five largest public and charitable funders adopt a published burden-weighted target with a 10% annual rebalancing rule, the ratio of research spend per death between the best- and worst-funded common cancers falls by at least half within five years, and grant applications in under-funded cancers rise in proportion.","rationale":"Portfolio targets work where they are transparent and measured: the UK Research Councils shifted spending towards dementia after a published burden comparison, and Gavi rebalanced vaccine investment using disease-burden weights. Peer review alone cannot rebalance because it scores proposals, not portfolios; the proposals that arrive already reflect where money has been.","test":"One funder pilots the formula on a defined pot (for example 20% of new awards) for three years, tracks application volume, success rates and quality scores by cancer, and compares the burden alignment of the pilot pot with the rest of its portfolio.","maturity":"speculative","actor":"policy","cost":"small","horizonYears":3},{"id":"idea-reg-patent-buyout-prize","kind":"idea","name":"Buy out the patent on a curative cancer drug and sell it at generic prices","aka":[],"tldr":"Governments and philanthropies would pay a company a one-off lump sum, set by auction to reflect the drug's social value, for the patent on a cancer drug with a large benefit in a common cancer, then let generic makers supply it worldwide at competitive prices. A pilot fund would buy out one or two oncology patents.","summary":"Patent buyouts (proposed by Kremer and others) replace monopoly pricing with a lump sum reflecting the drug's social value, after which the drug enters generic competition. Cancer drugs with large survival benefits in common cancers (for example adjuvant immunotherapy or a highly effective targeted agent) are candidates where the deadweight loss of high prices is largest. The proposal is a pilot fund, capitalised by a coalition of governments and philanthropies, that runs an auction-based valuation and buys out one or two oncology patents for global generic supply, with a prize element for the developer.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Prices and value): Prasad, De Jesús & Mailankody, The high price of anticancer drugs: origins, implications, barriers, solutions (Nat Rev Clin Oncol 2017)","url":"https://doi.org/10.1038/nrclinonc.2017.31"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-drug-pricing","b-global-access"],"keyPapers":["paper-prasad-nat-rev-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A buyout of a widely used oncology drug increases the number of patients treated worldwide at least fivefold within three years at a total public cost lower than five years of monopoly spend in high-income markets alone.","rationale":"For drugs with proven large benefit, the monopoly period wastes lives without serving its purpose of discovering whether the drug works; a lump sum preserves the innovation reward and removes the access barrier.","test":"Commission an independent valuation and feasibility study for two candidate drugs approaching mid-patent life, negotiate with the patent holder, and execute one buyout with global access tracking.","maturity":"speculative","actor":"philanthropy","cost":"large","horizonYears":5},{"id":"idea-caix-theranostics","kind":"idea","name":"CAIX theranostics: 89Zr-girentuximab PET and 177Lu/225Ac-girentuximab therapy","aka":[],"tldr":"Almost every clear-cell kidney cancer carries the CAIX protein. Image it with one radioactive antibody, then treat with the same antibody carrying a therapeutic isotope.","summary":"Nearly every clear-cell renal cell carcinoma expresses carbonic anhydrase IX as a direct consequence of VHL loss, so the antigen is near-universal and stable. This theranostic idea images it with 89Zr-girentuximab PET, validated for diagnosis in ZIRCON, and then treats with the same antibody carrying 177Lu for beta emission or 225Ac for targeted alpha therapy. The rationale combines a stable target, the PSMA precedent in prostate cancer, and radiation-induced immunogenic cell death in a cancer that already responds to immunotherapy. STARLITE-1 and STARLITE-2 are testing 177Lu-girentuximab with nivolumab or cabozantinib, and the proposed test is a randomised phase 2 of 177Lu-girentuximab plus nivolumab versus nivolumab alone; Telix Pharmaceuticals is the linked company.","asOf":"2026-09-07","links":[{"label":"Shuch et al., ZIRCON: 89Zr-girentuximab PET-CT imaging of clear-cell renal cell carcinoma (Lancet Oncology 2024)","url":"https://doi.org/10.1016/S1470-2045(24)00402-9"}],"tags":[],"related":[],"cancers":["rcc"],"sections":[],"technologies":["caix-pet","radioligand-therapy","targeted-alpha-therapy","radioimmunotherapy"],"targets":["hif2a"],"drugs":[],"companies":["telix"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-shuch-lancet-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"177Lu- or 225Ac-girentuximab produces objective responses in ≥25% of heavily pretreated clear-cell RCC patients selected by CAIX PET, and synergises with PD-1 blockade.","rationale":"Stable antigen, theranostic pairing proven in prostate cancer (PSMA), and radiation-induced immunogenic cell death in an immunotherapy-responsive tumour.","test":"Randomised phase 2 of 177Lu-girentuximab + nivolumab vs nivolumab after IO-TKI progression, PET-selected.","maturity":"early-clinical"},{"id":"idea-tr2-her2-low-reference-materials","kind":"idea","name":"Calibrated reference slides so every lab scores HER2-low the same way","aka":[],"tldr":"Whether a breast cancer counts as HER2-low, and so qualifies for trastuzumab deruxtecan, turns on the least reproducible step of the HER2 stain, score 1+ versus 0. Cell-line microarrays with a known quantity of HER2 protein per cell, run alongside clinical slides, would anchor every laboratory to a physical standard.","summary":"T-DXd approval for HER2-low created a treatment decision at IHC 1+ versus 0, the least reproducible part of the HER2 scale, with inter-pathologist agreement reported as poor. Cell-line microarrays with quantified HER2 protein per cell, distributed as reference materials and run alongside clinical slides (as NordiQC and CAP do for proficiency testing), would anchor staining intensity and scoring to a physical standard, complemented by digital image analysis calibrated to the same materials.","asOf":"2026-09-08","links":[{"label":"NordiQC","url":"https://www.nordiqc.org/"}],"tags":[],"related":["her2-low","idea-ai-her2-low-scoring"],"cancers":[],"sections":[],"technologies":["histopathology-ihc","digital-pathology-ai"],"targets":[],"drugs":["trastuzumab-deruxtecan"],"companies":[],"institutions":[],"pathways":[],"terms":["ihc"],"trials":["destiny-breast04","destiny-breast06"],"people":[],"bottlenecks":["b-biomarker-validation"],"keyPapers":["paper-destiny-breast06-nejm-2024"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Laboratories using calibrated reference materials will show inter-laboratory agreement on HER2 0 versus 1+ above 85%, compared with the 60 to 70% reported in current concordance studies.","rationale":"Reference materials transformed reproducibility in clinical chemistry. Pathology has proficiency schemes but few quantitative anchors for low-level protein expression.","test":"Distribute reference arrays to 50 laboratories with a blinded set of clinical cases; measure agreement with and without reference calibration.","maturity":"early-clinical","actor":"regulator","cost":"small","horizonYears":2},{"id":"idea-drugging-myc","kind":"idea","name":"Can MYC be drugged directly, and will patients tolerate it?","aka":[],"tldr":"MYC drives half of all cancers but has no pocket for a drug and is needed by normal cells too. The first direct MYC blockers are in trials; the question is whether there is a therapeutic window.","summary":"This open question asks whether MYC can be drugged directly and tolerated: MYC drives half of all cancers but has no pocket for a drug and is needed by normal cells too. OMO-103 (Omomyc) showed safety and disease stabilisation in phase 1, and mouse studies showed reversible toxicity in proliferating tissues, but human tolerance at effective doses is unproven. The hypothesis is that transient, intermittent MYC inhibition achieves regression in MYC-amplified cancers while normal tissues recover between doses, and PD-1 blockade may add benefit via CD47 and PD-L1. The test is a randomised phase 2 of OMO-103 plus chemotherapy in MYC-amplified Pancreatic ductal adenocarcinoma and Triple-negative breast cancer (TNBC).","asOf":"2026-09-08","links":[{"label":"Garralda et al., MYC targeting by OMO-103 in solid tumours: a phase 1 trial (Nature Medicine 2024)","url":"https://doi.org/10.1038/s41591-024-02805-1"}],"tags":["mechanism","open-question"],"related":[],"cancers":["pancreatic","tnbc","neuroblastoma"],"sections":[],"technologies":[],"targets":["cd47"],"drugs":[],"companies":[],"institutions":["vall-dhebron","ucsf"],"pathways":["myc"],"terms":[],"trials":["nct05482893"],"people":[],"bottlenecks":[],"keyPapers":["paper-garralda-nat-med","paper-cd47-pancreatic-pharmacol-res-2022","paper-cd47-neuroblastoma-curr-oncol-2024"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Transient, incomplete MYC inhibition (intermittent dosing) achieves tumour regression in MYC-amplified cancers while normal tissues recover between doses, yielding a usable therapeutic index.","rationale":"Soucek's Omomyc mouse models tolerated systemic MYC inhibition; MYC-addicted tumours show non-oncogene addiction to MYC dosage; combination with PD-1 blockade may add via CD47/PD-L1 downregulation.","test":"Phase 2 randomised OMO-103 plus chemotherapy vs chemotherapy in MYC-amplified metastatic PDAC and TNBC with intermittent schedules; pharmacodynamic MYC target-gene signatures in paired biopsies.","maturity":"early-clinical"},{"id":"idea-tdxd-first-then-nothing","kind":"idea","name":"Can T-DXd alone cure early HER2-positive disease?","aka":[],"tldr":"If Enhertu produces complete responses in two-thirds of patients before surgery, a trial should test whether some need no chemotherapy, antibodies, or even radiation afterwards.","summary":"The idea is a response-adapted trial in early HER2-positive breast cancer that gives trastuzumab deruxtecan alone before surgery and, for patients who reach a pathological complete response, drops everything else: no further chemotherapy, antibodies alone or observation only. A pathological complete response predicts near-cure, PHERGain proved imaging-adapted omission is feasible, and T-DXd's complete-response rate approaches that of the best chemotherapy regimens. DESTINY-Breast11, where neoadjuvant T-DXd was followed by THP, and DESTINY-Breast05 bracket the curative setting. The test would be a single-arm study then randomised de-escalation, with PET and ctDNA as early response markers and lung toxicity as the safety endpoint.","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT05113251: DESTINY-Breast11","url":"https://clinicaltrials.gov/study/NCT05113251"},{"label":"ClinicalTrials.gov NCT04622319: DESTINY-Breast05","url":"https://clinicaltrials.gov/study/NCT04622319"}],"tags":[],"related":[],"cancers":["breast-her2-positive"],"sections":[],"technologies":[],"targets":[],"drugs":["trastuzumab-deruxtecan","trastuzumab","pertuzumab"],"companies":[],"institutions":[],"pathways":[],"terms":["pcr"],"trials":["destiny-breast11","destiny-breast05","phergain"],"people":[],"bottlenecks":[],"keyPapers":["paper-trastuzumab-breast-her2-positive-n-engl-j-med-2005","paper-hera-b31-n9831-n-engl-j-med-2005","paper-trastuzumab-breast-her2-positive-n-engl-j-med-2011"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Neoadjuvant T-DXd monotherapy followed by response-adapted de-escalation (no further chemotherapy; antibodies only, or observation) achieves 3-year iDFS ≥92% in pCR patients.","rationale":"pCR after HER2-directed therapy predicts near-cure; PHERGain proved imaging-adapted omission is feasible; T-DXd's pCR rate approaches the best chemotherapy-containing regimens.","test":"Single-arm then randomised de-escalation study with ctDNA and PET as early response markers; ILD monitoring as the safety endpoint.","maturity":"early-clinical"},{"id":"idea-interception-vaccines","kind":"idea","name":"Cancer interception vaccines for high-risk carriers","aka":[],"tldr":"Vaccinate people with BRCA or Lynch mutations against the antigens their future cancers will express, before any cancer exists.","summary":"Vaccinate people with BRCA or Lynch mutations against the antigens their future cancers will express, before any cancer exists. Lynch syndrome tumours share recurrent frameshift neoantigens and BRCA1 tumours are basal-like with predictable antigens, so vaccination could reduce adenoma and cancer incidence in carriers whose immune systems are intact and tumour burden is zero. Nous-209 for Lynch syndrome and the alpha-lactalbumin vaccine for TNBC from Cleveland Clinic are in early trials, and prevention needs only modest efficacy to be cost-effective. The test is a randomised placebo-controlled trial in Lynch carriers with colonoscopic adenoma incidence as the endpoint. At early-clinical maturity it addresses the bottleneck Inherited risk is mostly unidentified.","asOf":"2026-09-04","links":[{"label":"CAPP2: two years of aspirin cuts bowel cancer in Lynch syndrome by more than a third over 10 years (The Lancet 2020)","url":"https://doi.org/10.1016/S0140-6736(20)30366-4"}],"tags":[],"related":[],"cancers":["colorectal","tnbc"],"sections":[],"technologies":["shared-antigen-vaccine","chemoprevention","germline-testing"],"targets":["brca"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Vaccination of Lynch carriers against recurrent frameshift peptides reduces adenoma and cancer incidence over 5 years.","rationale":"Immune system is intact, tumour burden zero, antigens predictable; prevention needs only modest efficacy to be cost-effective.","test":"Randomised placebo-controlled trial in Lynch carriers with colonoscopic adenoma incidence endpoint.","maturity":"early-clinical"},{"id":"idea-prev-ehr-symptom-signature-prompts","kind":"idea","name":"Cancer risk scores running automatically in GP records to prompt urgent referral","aka":[],"tldr":"Computers can combine minor symptoms, blood tests and age into a cancer risk score in the background. Showing that score to the GP could get more people referred earlier.","summary":"QCancer and similar algorithms exist but are rarely used because they need manual entry. Propose EHR-embedded, passively computed risk scores with a threshold-triggered prompt, tested in a randomised trial with stage at diagnosis and emergency presentation as endpoints, following the template of the UK ERICA cluster trial.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The hardest cancers are found late): Crosby et al., Early detection of cancer (Science 2022)","url":"https://doi.org/10.1126/science.aay9040"}],"tags":[],"related":[],"cancers":[],"sections":["early-detection"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-early-detection","b-care-fragmentation"],"keyPapers":["paper-crosby-science"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Passive risk-score prompts increase the proportion of cancers diagnosed at stage I-II by at least 5 percentage points and reduce emergency presentations by at least 15% without doubling referral volume.","rationale":"The evidence gap is implementation, not algorithm accuracy.","test":"Cluster RCT across 500 practices over two years with registry-linked outcomes.","maturity":"early-clinical","actor":"clinic","cost":"medium","horizonYears":3},{"id":"idea-prev-alcohol-cancer-warning-labels","kind":"idea","name":"Cancer warnings on alcohol labels, evaluated as a natural experiment","aka":[],"tldr":"Most people do not know alcohol causes seven cancers. Ireland is putting cancer warnings on bottles; other countries should follow and measure the effect on drinking.","summary":"Most people do not know that alcohol causes seven cancers, so this idea follows Ireland's Public Health (Alcohol) Act, which mandates cancer warnings on labels, with EU-wide adoption on a staggered timetable that allows difference-in-differences evaluation of awareness and per-capita consumption. The Yukon labelling experiment reduced sales, tobacco labelling sets the precedent, the cost is low, and industry opposition is consistent with the expected effect. The test is a pre-registered evaluation across adopting and non-adopting EU states. Being tested at scale, it addresses the bottlenecks Prevention we already have is not deployed and Misinformation and unproven therapies, and links to breast, colorectal, oesophageal and liver cancer.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Prevention we already have is not deployed): Islami et al., Proportion of cancer attributable to modifiable risk factors (CA 2018)","url":"https://doi.org/10.3322/caac.21440"}],"tags":[],"related":[],"cancers":["breast-hr-positive","colorectal","esophageal","hcc"],"sections":["prevention"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption","b-misinformation"],"keyPapers":["paper-islami-ca-cancer-j-clin"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Cancer warnings increase awareness of the alcohol-cancer link by at least 20 percentage points and reduce per-capita consumption by at least 3% within three years.","rationale":"Tobacco labelling precedent, low cost, and industry opposition consistent with expected effect.","test":"Run a pre-registered evaluation across adopting and non-adopting EU states.","maturity":"being-tested-at-scale","actor":"policy","cost":"small","horizonYears":3},{"id":"idea-reg-price-anchored-to-mcbs","kind":"idea","name":"Cap public prices for new cancer drugs to tiers of the ESMO and ASCO value scales","aka":[],"tldr":"Oncology societies already grade how much benefit each new drug gives. Payers should tie the maximum price they pay to that grade.","summary":"The ESMO Magnitude of Clinical Benefit Scale and ASCO Value Framework grade drugs by survival gain, quality of life and toxicity, but prices bear little relation to the grades; several analyses find no correlation between price and benefit. The proposal is for a coalition of public payers to publish a price corridor per benefit tier (for example a multiple of GDP per capita per life-year gained for grade 4-5 versus a much lower ceiling for grade 1-2) and to make the tier a binding input to negotiation, with prices revisited when confirmatory data change the grade.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Prices and value): Prasad, De Jesús & Mailankody, The high price of anticancer drugs: origins, implications, barriers, solutions (Nat Rev Clin Oncol 2017)","url":"https://doi.org/10.1038/nrclinonc.2017.31"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["esmo","asco"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-drug-pricing","b-incentive-misalignment"],"keyPapers":["paper-prasad-nat-rev-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Payers adopting tiered ceilings pay prices correlated with benefit (Spearman rho above 0.5, from near zero today) and see lower growth in oncology drug spend without reducing the number of high-benefit drugs reimbursed.","rationale":"Transparent, benefit-linked ceilings give manufacturers a predictable target and reward developing drugs with large effects; the absence of any benefit-price relationship is the clearest symptom of a broken market.","test":"Retrospectively apply tiered ceilings to the last decade of oncology approvals in one country to model spend and access; then adopt prospectively in a coalition of two or three payers and measure correlation and spend after three years.","maturity":"speculative","actor":"payer","cost":"small","horizonYears":3},{"id":"idea-cost-part-b-cap","kind":"idea","name":"Cap what Original Medicare patients pay for Part B cancer drugs","aka":[],"tldr":"Oral cancer drugs under Part D now have a yearly cap of $2,100, but infused drugs under Part B still carry 20% coinsurance with no limit; a Part B cap would close the biggest hole left in Medicare cancer coverage.","summary":"The Inflation Reduction Act capped Part D out-of-pocket spending ($2,000 in 2025, $2,100 in 2026) but left Part B untouched. A patient on an infused checkpoint inhibitor without Medigap or Medicaid owes 20% of the Medicare-approved amount indefinitely. Options include a Part B out-of-pocket cap funded by a premium adjustment, or a guaranteed-issue window for Medigap after a cancer diagnosis so that people can buy the protection that already exists.","asOf":"2026-09-10","links":[{"label":"Medicare.gov: Chemotherapy coverage","url":"https://www.medicare.gov/coverage/chemotherapy"},{"label":"Medicare.gov: Medigap","url":"https://www.medicare.gov/health-drug-plans/medigap"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["financial-toxicity"],"trials":[],"people":[],"bottlenecks":["b-drug-pricing"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A Part B cap or diagnosis-triggered Medigap guaranteed issue will reduce the share of Original Medicare cancer patients with out-of-pocket drug spending above $5,000 a year by more than half.","rationale":"Medicare Advantage plans already carry an in-network cap ($9,350 in 2025), so the actuarial mechanics are proven; the gap is in Original Medicare.","test":"Actuarial modelling by CMS and the Congressional Budget Office, followed by a state-level Medigap guaranteed-issue pilot (several states already require it) evaluated on take-up and out-of-pocket spending.","maturity":"speculative","actor":"policy","cost":"large","horizonYears":4},{"id":"idea-nl-diet-covariates-io-trials","kind":"idea","name":"Capture diet, fibre and antibiotic exposure in every immunotherapy pivotal trial","aka":[],"tldr":"Gut bacteria appear to influence whether immunotherapy works, and diet and antibiotics shape gut bacteria. Yet almost no drug trial records what patients ate or which antibiotics they took. Recording it would cost almost nothing.","summary":"Fibre intake, probiotic use, antibiotics and proton-pump inhibitors are each associated with checkpoint-inhibitor outcomes in observational cohorts, but the data come from single centres with recall questionnaires. Pivotal trials enrol tens of thousands of patients under protocol with concomitant medication logs already captured; adding a short validated diet screener and banking a baseline stool sample would generate the largest and cleanest dataset on host factors in immunotherapy, and allow stratified or covariate-adjusted analyses that could explain part of the variability in response.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (No one can predict who responds to immunotherapy): Haslam & Prasad (JAMA Network Open 2019)","url":"https://doi.org/10.1001/jamanetworkopen.2019.2535"}],"tags":[],"related":["idea-bio2-antibiotic-stewardship-io","idea-bio2-fibre-diet-io-trial"],"cancers":["melanoma","nsclc","rcc"],"sections":["nutrition-lifestyle","immunotherapy"],"technologies":["dietary-fibre-microbiome-io","probiotics-antibiotic-stewardship-io","checkpoint-inhibitor"],"targets":[],"drugs":["pembrolizumab","nivolumab"],"companies":[],"institutions":[],"pathways":[],"terms":["gut-microbiome-diversity","dietary-pattern-scores"],"trials":[],"people":[],"bottlenecks":["b-immunotherapy-response","b-trial-design","b-data-silos"],"keyPapers":["paper-haslam-jama-netw-open"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Across pooled pivotal checkpoint-inhibitor trials, baseline fibre intake and peri-treatment antibiotic exposure are independent predictors of progression-free survival with effect sizes comparable to PD-L1 expression, and adjusting for them reduces between-trial heterogeneity.","rationale":"Regulators already require concomitant medication recording; FDA and EMA have encouraged patient-reported outcome and biomarker collection. A 10-item diet screener and a stool kit add minutes and a few hundred dollars per patient against trial costs of tens of thousands.","test":"Pilot in two ongoing cooperative-group immunotherapy trials with pre-specified analysis; if predictive value is confirmed, FDA and EMA guidance recommending standardised diet and antibiotic capture in immuno-oncology trials, with pooled analysis through Project Data Sphere or similar.","maturity":"speculative","actor":"regulator","cost":"small","horizonYears":3},{"id":"idea-acc-cardiometabolic-clinic-hormone-therapy","kind":"idea","name":"Cardiometabolic screening and treatment for survivors on long-term hormone therapy","aka":[],"tldr":"Hormone-blocking treatments for prostate and breast cancer, taken for years, raise the risk of diabetes, heart disease and bone fractures. Survivors on these drugs should get the same preventive care as diabetics.","summary":"Androgen deprivation therapy increases diabetes, cardiovascular events, and fractures; aromatase inhibitors affect bone and lipids. Millions of survivors take these drugs for years, but cardiometabolic risk management is rarely owned by anyone. A protocolised pathway with baseline and annual metabolic and bone assessment, and treatment to targets, delivered by nurses or pharmacists, would prevent a substantial burden of non-cancer morbidity.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Survivorship and late effects are neglected): NCI Office of Cancer Survivorship statistics","url":"https://cancercontrol.cancer.gov/ocs/statistics"}],"tags":[],"related":["prostate-roadmap","idea-prostate-other-cause-mortality-as-a-reported-service-outcome"],"cancers":["prostate","breast-hr-positive"],"sections":[],"technologies":["androgen-deprivation","endocrine-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-aging-comorbidity"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Protocolised cardiometabolic management for survivors on long-term hormone therapy will reduce major cardiovascular events and fragility fractures by at least 20% over five years compared with usual care.","rationale":"The risks are well quantified and the preventive treatments are cheap and proven in other populations; the failure is one of ownership between oncology and primary care.","test":"A cluster-randomised trial across 30 practices or clinics with cardiovascular events, fractures, and treatment-to-target rates as endpoints.","maturity":"early-clinical","actor":"clinic","cost":"small","horizonYears":3},{"id":"idea-acc-caregiver-training-as-covered-service","kind":"idea","name":"Caregiver training and respite as a covered service in cancer care for older patients","aka":[],"tldr":"Older cancer patients depend on family carers who receive no training or support. Paying for carer training and short breaks would keep patients at home and out of hospital.","summary":"Informal caregivers manage medications, symptoms, and appointments for most older patients with cancer, often with high distress and no preparation. Structured caregiver training (symptom recognition, medication management, when to call) and respite services reduce caregiver burden and, in some studies, patient hospitalisations. Making these reimbursable services within cancer care would recognise carers as part of the care team.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Older and multimorbid patients are excluded and undertreated): Mohile et al., Evaluation of geriatric assessment and management on toxic effects of cancer treatment (GAP70+, Lancet 2021)","url":"https://doi.org/10.1016/S0140-6736(21)01789-X"}],"tags":[],"related":[],"cancers":[],"sections":["supportive-care"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-aging-comorbidity","b-patient-voice"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Covered caregiver training and respite will reduce unplanned admissions of older patients by at least 15% and reduce caregiver distress scores, at net cost savings.","rationale":"Caregiver interventions have evidence in dementia and heart failure; older cancer patients have similar dependency with more acute crises.","test":"A randomised trial of covered caregiver support versus usual care for 800 patients over 75 with admissions, caregiver distress, and cost as endpoints.","maturity":"early-clinical","actor":"payer","cost":"medium","horizonYears":3},{"id":"idea-acc-abandonment-stipends","kind":"idea","name":"Cash for transport and food to stop families abandoning curative treatment","aka":[],"tldr":"Treatment abandonment is the leading cause of treatment failure for childhood cancer in much of the low- and middle-income world, driven by bus fares, lost income and the cost of food and lodging. Conditional cash, transport vouchers and family accommodation have cut abandonment sharply in Central America, East Africa and India, and should be funded in every curative protocol.","summary":"Treatment abandonment is the leading cause of treatment failure for childhood cancer in much of the low- and middle-income world, and is driven by transport cost, lost income, and lodging. Programmes providing conditional cash, transport vouchers, and family accommodation (in Central America, East Africa, and India) have cut abandonment dramatically at low cost. The proposal is to make an abandonment-prevention package a standard, funded component of every curative protocol in LMIC centres and to report abandonment as a quality indicator.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Most of the world has almost no cancer care): WHO fact sheet, Cancer","url":"https://www.who.int/news-room/fact-sheets/detail/cancer"}],"tags":[],"related":[],"cancers":["all-leukemia","hodgkin-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-global-access","b-patient-voice"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Centres implementing a standard stipend and accommodation package will reduce treatment abandonment in paediatric ALL and Hodgkin lymphoma below 5% from baselines often above 20%, with a cost per additional cure under $2,000.","rationale":"Conditional cash transfers have strong evidence for adherence in TB and HIV; abandonment data from paediatric oncology programmes show large effects from modest support.","test":"Stepped introduction across a national paediatric network with abandonment rate, event-free survival, and cost per averted abandonment as endpoints.","maturity":"being-tested-at-scale","actor":"philanthropy","cost":"small","horizonYears":2},{"id":"idea-bio2-remote-weight-step-monitoring","kind":"idea","name":"Catch wasting early with a smart scale and a step counter","aka":[],"tldr":"Slow weight loss and falling daily activity are the first signs of cancer wasting, and both can be measured at home. An alert could bring help months earlier.","summary":"Home weight and activity monitoring is cheap and acceptable, and remote symptom monitoring has already improved survival and quality of life in randomised oncology trials. Trajectory-based alerts on weight and step count would detect functional decline weeks to months before clinic visits, at which point nutrition and exercise interventions still work.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Cachexia, toxicity and the limits of the patient): Fearon et al., Definition and classification of cancer cachexia (Lancet Oncology 2011)","url":"https://doi.org/10.1016/S1470-2045(10)70218-7"}],"tags":[],"related":[],"cancers":["pancreatic","nsclc"],"sections":[],"technologies":["exercise-oncology","geriatric-assessment"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-cachexia-supportive","b-patient-voice","b-toxicity-qol"],"keyPapers":["paper-fearon-lancet-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Trajectory-triggered alerts from home weight and activity data lead to supportive care intervention a median of two months earlier and reduce unplanned admissions compared with clinic-based assessment.","rationale":"Patient-reported outcome monitoring with alerts improved survival in randomised trials, showing that earlier detection of deterioration changes outcomes. Weight and steps are objective, continuous and require no patient effort beyond wearing a device.","test":"A randomised trial of monitored versus usual follow-up in patients starting palliative-intent chemotherapy, with time to supportive care intervention and unplanned admissions as endpoints.","maturity":"speculative","actor":"patients","cost":"small","horizonYears":3},{"id":"idea-prev-hpv-male-catchup-oropharynx","kind":"idea","name":"Catch-up HPV vaccination for men to prevent throat cancer","aka":[],"tldr":"HPV throat cancer now exceeds cervical cancer in some countries and mostly affects men, who were not vaccinated. Vaccinating men up to 45 could reduce it.","summary":"HPV throat cancer now exceeds cervical cancer in some countries and mostly affects men who were never vaccinated, so this idea offers catch-up HPV vaccination to men up to age 45. HPV vaccination reduces oral HPV16 prevalence, oropharyngeal cancer incidence in men is rising, and the vaccine is safe in adults; the causal chain is strong despite the long latency. Oral HPV prevalence would serve as the intermediate endpoint with modelled cancer reduction. The test is prevalence surveys, modelling and cost-effectiveness analysis. Speculative in maturity, it addresses the bottleneck Prevention we already have is not deployed and links to HPV vaccination and head and neck cancer.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Prevention we already have is not deployed): Islami et al., Proportion of cancer attributable to modifiable risk factors (CA 2018)","url":"https://doi.org/10.3322/caac.21440"}],"tags":[],"related":[],"cancers":["head-and-neck"],"sections":["prevention"],"technologies":["hpv-vaccine"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption"],"keyPapers":["paper-islami-ca-cancer-j-clin"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Catch-up vaccination of men aged 27-45 reduces oral HPV16 prevalence by at least half in the vaccinated and oropharyngeal cancer incidence by at least 20% within 20 years.","rationale":"Long latency but a strong causal chain, and the vaccine is safe in adults.","test":"Prevalence surveys, modelling, and cost-effectiveness analysis.","maturity":"speculative","actor":"policy","cost":"medium","horizonYears":10},{"id":"idea-cd30-car-t-hodgkin","kind":"idea","name":"CD30 CAR-T for multiply relapsed Hodgkin lymphoma","aka":[],"tldr":"Engineer T cells against CD30 for the few patients who fail brentuximab, PD-1 blockade and transplant.","summary":"For the few patients with Hodgkin lymphoma who relapse after brentuximab vedotin, PD-1 blockade and transplant, this idea proposes CAR-T cells engineered against CD30. CD30 is expressed on nearly all Reed-Sternberg cells, shed CD30 does not block binding at therapeutic doses, and the inflamed microenvironment supports CAR-T trafficking. Phase 1/2 studies at UNC and Baylor and of the Tessa Therapeutics TT11 product produced responses and complete remissions in a substantial share of patients, although durability was modest, and the pivotal CHARIOT study was halted for business reasons in 2023 to 2024. The hypothesis is that CD30 CAR-T after PD-1 failure yields durable remissions and that PD-1 blockade prolongs persistence, tested in a randomised phase 2, at an early clinical stage.","asOf":"2026-09-07","links":[{"label":"Ramos et al., Anti-CD30 CAR-T cell therapy in relapsed and refractory Hodgkin lymphoma (Journal of Clinical Oncology 2020)","url":"https://doi.org/10.1200/JCO.20.01342"}],"tags":[],"related":[],"cancers":["hodgkin-lymphoma"],"sections":[],"technologies":["car-t"],"targets":["cd30"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-cd30-hodgkin-lymphoma-j-clin-oncol-2020","paper-cd30-hodgkin-lymphoma-blood-cancer-j-2017","paper-cd30-hodgkin-lymphoma-j-clin-oncol-2015"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"CD30 CAR-T after PD-1 failure yields durable CR in ≥40% of patients with an acceptable CRS profile, and combination with PD-1 blockade prolongs persistence.","rationale":"CD30 is near-universal on Reed-Sternberg cells and shed CD30 does not block binding at therapeutic doses; the inflamed microenvironment supports CAR-T trafficking.","test":"Randomised phase 2 of CD30 CAR-T ± nivolumab vs investigator's choice in triple-refractory disease.","maturity":"early-clinical"},{"id":"idea-cd8-pet-io","kind":"idea","name":"CD8 PET to stop or switch immunotherapy early","aka":[],"tldr":"Scan for T cells inside the tumour a few weeks after starting immunotherapy. If they have not arrived, change course.","summary":"Scan for T cells inside the tumour a few weeks after starting immunotherapy, and change course if they have not arrived. Tracers such as 89Zr-crefmirlimab, a CD8 minibody, and 18F-AraG image T-cell infiltration and activation, and an early increase has tracked response in phase 2 studies. Response to checkpoint blockade requires T-cell infiltration, CT changes lag by months and pseudoprogression confounds RECIST, so an absent CD8 PET signal at week 4 could identify non-responders early. The test is a prospective trial in NSCLC or melanoma with week-4 CD8 PET, randomising PET non-responders to continue or switch. At early-clinical maturity it addresses the bottleneck No one can predict who responds to immunotherapy.","asOf":"2026-09-04","links":[{"label":"Farwell et al., CD8-targeted PET imaging of tumour-infiltrating T cells in patients with cancer: a phase 1 first-in-human study of 89Zr-Df-IAB22M2C (Journal of Nuclear Medicine 2021)","url":"https://doi.org/10.2967/jnumed.121.262485"}],"tags":[],"related":[],"cancers":["melanoma","nsclc"],"sections":[],"technologies":["immuno-pet","checkpoint-inhibitor"],"targets":["pd1"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-farwell-j-nucl-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Absence of CD8 PET increase at week 4 identifies non-responders with >85% specificity, enabling early switch to alternative therapy.","rationale":"Response to checkpoint blockade requires T-cell infiltration; CT changes lag by months; pseudoprogression confounds RECIST.","test":"Run a prospective trial in NSCLC or melanoma with week-4 CD8 PET; randomise PET-non-responders to continue vs switch.","maturity":"early-clinical"},{"id":"idea-cdk4-selective-first-line","kind":"idea","name":"CDK4-selective inhibitors as the new first-line backbone","aka":[],"tldr":"If a CDK4-only drug matches CDK4/6 inhibitors on efficacy with less neutropenia, continuous dosing and better adherence could translate into longer control.","summary":"The idea is to replace palbociclib, ribociclib and abemaciclib with a CDK4-selective drug such as atirmociclib, paired with letrozole, as the first-line backbone in HR-positive, HER2-negative breast cancer. Luminal breast cancer depends on cyclin D1 and CDK4, whereas CDK6 dependence is mainly haematopoietic, so sparing CDK6 should remove the neutropenia that forces dose holds and reductions with the current class. The hypothesis is non-inferior or superior progression-free survival with fewer severe blood-count events and higher dose intensity, so that continuous dosing and better adherence give longer control. FOURLIGHT-1 showed activity after CDK4/6 failure, and the enrolling phase 3 FOURLIGHT-3 trial is the test; the idea is at an early clinical stage.","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT06105632: FOURLIGHT-1","url":"https://clinicaltrials.gov/study/NCT06105632"}],"tags":[],"related":[],"cancers":["breast-hr-positive"],"sections":[],"technologies":[],"targets":["cdk4-6"],"drugs":["atirmociclib","palbociclib","ribociclib","abemaciclib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["fourlight-1"],"people":[],"bottlenecks":[],"keyPapers":["paper-paloma-2-n-engl-j-med-2016","paper-monaleesa-2-n-engl-j-med-2016","paper-palbociclib-breast-hr-positive-lancet-oncol-2015"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"CDK4-selective inhibition + letrozole is non-inferior or superior in PFS to CDK4/6 + letrozole in first-line HR+/HER2- disease, with fewer grade 3+ haematologic events and higher relative dose intensity.","rationale":"Luminal breast cancer depends on cyclin D1-CDK4; CDK6 dependence is mainly haematopoietic. FOURLIGHT-1 showed activity after CDK4/6 failure.","test":"FOURLIGHT-3 phase 3 (enrolling); secondary analyses of dose intensity and quality of life.","maturity":"early-clinical"},{"id":"idea-moon-certified-decision-aids","kind":"idea","name":"Certified decision aids required for every preference-sensitive cancer decision","aka":[],"tldr":"For choices where the right answer depends on what the patient values (watching a slow prostate cancer, adjuvant chemo at 80, breast reconstruction), a tested decision aid becomes part of the consultation.","summary":"Decision aids improve knowledge, accuracy of risk perception and value-concordant choices in Cochrane reviews, yet are rarely used. The proposal is that guideline bodies designate a list of preference-sensitive decisions, that decision aids meeting IPDAS standards are certified for each, and that use is documented and audited like consent. A shared decision quality metric (knowledge plus concordance between stated values and chosen option) becomes a quality indicator.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Patients lack understanding, navigation and agency): Basch et al., Overall survival results of a trial assessing patient-reported outcomes for symptom monitoring during routine cancer treatment (JAMA 2017)","url":"https://doi.org/10.1001/jama.2017.7156"}],"tags":[],"related":[],"cancers":["prostate","breast-hr-positive"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-patient-voice","b-overdiagnosis"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Mandated certified aids raise decision quality scores, cut decisional regret at one year, and shift choices towards less intensive options in low-risk disease without worsening outcomes.","rationale":"In the absence of aids, choices track the clinician's habits and the local supply of services more than patient values, which is one mechanism of overtreatment.","test":"Cluster-randomised implementation trial for three decisions (low-risk prostate cancer, DCIS, adjuvant chemotherapy in patients over 75) measuring decision quality, regret and treatment mix.","maturity":"early-clinical","actor":"clinic","cost":"medium","horizonYears":3},{"id":"idea-tr2-ctdna-reference-plasma","kind":"idea","name":"Certified reference samples to benchmark every tumour-DNA blood test","aka":[],"tldr":"Dozens of companies sell blood tests for tumour DNA and they report different results on the same sample. Government-issued reference samples with known amounts of tumour DNA would expose the differences.","summary":"ctDNA assays differ in limit of detection, variant calling and reporting; head-to-head comparisons on clinical samples show discordance, especially at low variant allele fractions where MRD decisions are made. A national metrology institute issuing certified reference plasma (fragmented DNA with defined variants at defined allele fractions, including sub-0.1% levels) and requiring assays to report performance on them in labelling would make claims comparable and detect drift over time.","asOf":"2026-09-08","links":[{"label":"FDA SEQC2 project (page moved; nearest live section)","url":"https://www.fda.gov/science-research/bioinformatics-tools/"}],"tags":[],"related":["guardant-health","natera","idea-tr2-liquid-biopsy-challenge"],"cancers":[],"sections":[],"technologies":["liquid-biopsy","mrd-testing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["ctdna","vaf","mrd"],"trials":[],"people":[],"bottlenecks":["b-biomarker-validation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Assays that report performance on certified reference plasma will show a spread of sensitivity at 0.1% allele fraction wide enough to change clinical decisions, and the requirement will drive convergence within three years.","rationale":"Certified reference materials underpin every quantitative clinical assay; ctDNA is being used for treatment decisions without them.","test":"Produce reference plasma at four allele fraction levels; run a blinded round across ten commercial assays; publish results.","maturity":"early-clinical","actor":"regulator","cost":"small","horizonYears":2},{"id":"idea-data-oncology-api-certification","kind":"idea","name":"Certify every oncology software product for a standard bulk data export","aka":[],"tldr":"Regulators would test and certify that every hospital cancer system can export its records in a standard format, the way electrical appliances are certified safe.","summary":"The US ONC certification programme already requires certified EHRs to support FHIR Bulk Data (Flat FHIR) export for the USCDI core data set, but oncology-specific systems (treatment planning, chemotherapy prescribing, molecular reporting, radiotherapy oncology information systems) are largely outside it. The proposal extends certification criteria to oncology systems with mCODE and DICOM-RT profiles, tested by a public conformance suite, so that a cancer centre can pull all of a patient's data through one standard interface.","asOf":"2026-09-08","links":[{"label":"ONC Health IT Certification Program","url":"https://www.healthit.gov/topic/certification-ehrs/certification-health-it"},{"label":"FHIR Bulk Data Access","url":"https://hl7.org/fhir/uv/bulkdata/"}],"tags":[],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":["varian","elekta"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-data-silos"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"If oncology systems must pass a public conformance test to be sold to publicly funded providers, integration cost per cancer centre for research data extraction falls by more than half within five years and the number of centres contributing to national datasets doubles.","rationale":"Certification with public conformance testing created the FHIR API ecosystem in US general medicine within a decade; the same lever has not been applied to oncology-specific vendors, which is where the richest data sit.","test":"Publish an open conformance test suite for oncology bulk export (mCODE plus DICOM-RT) and run it against the ten largest oncology systems; publish results. If vendors fail and do not fix within a year, that is the case for making certification mandatory in procurement.","maturity":"speculative","actor":"regulator","cost":"medium","horizonYears":4},{"id":"idea-prev-fragmentomics-first-tier","kind":"idea","name":"Cheap DNA fragment-pattern blood test as a first sieve before expensive cancer tests","aka":[],"tldr":"How DNA fragments in blood are chopped up differs in cancer and can be read with cheap, shallow sequencing. Used as a first sieve, it could cut the cost of population screening.","summary":"The way DNA fragments in blood are chopped up differs in cancer and can be read with cheap, shallow sequencing, so this idea uses cell-free DNA fragmentomics as a first sieve, with deep methylation testing reserved for the top tenth by risk. DELFI Diagnostics and Johns Hopkins have validated fragmentomics with low-coverage whole-genome sequencing and machine learning in high-risk lung cohorts. Cost per test rather than accuracy limits yearly population screening, and tiering is how HPV and cytology triage already works. The test re-analyses banked plasma from a prospective MCED cohort with both assays, then runs a prospective tiered pilot. At early-clinical maturity it addresses the bottleneck The hardest cancers are found late.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The hardest cancers are found late): Crosby et al., Early detection of cancer (Science 2022)","url":"https://doi.org/10.1126/science.aay9040"}],"tags":[],"related":[],"cancers":[],"sections":["early-detection"],"technologies":["liquid-biopsy","mced"],"targets":[],"drugs":[],"companies":["delfi-diagnostics"],"institutions":["johns-hopkins"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-early-detection"],"keyPapers":["paper-crosby-science"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A two-tier design achieves at least 90% of the sensitivity of universal deep methylation testing at 30% or less of the sequencing cost.","rationale":"Cost per test, not accuracy, limits yearly population screening; tiering is how HPV and cytology triage already works.","test":"Re-analyse banked plasma from a prospective MCED cohort with both assays; then run a prospective tiered pilot.","maturity":"early-clinical","actor":"industry","cost":"medium","horizonYears":4},{"id":"idea-tr1-registry-linked-os-followup","kind":"idea","name":"Cheap long-term survival follow-up by linking trial participants to registries","aka":[],"tldr":"Trials often stop following patients once the main result is in, so we never learn whether the drug extended life. Linking participants to national death and cancer registries costs almost nothing and would answer that question.","summary":"With participant consent at enrolment, trials link identifiers to national death indices and cancer registries so that OS and second-cancer follow-up continues indefinitely at negligible cost after study closure. Regulators require OS reporting at 5 and 10 years for drugs approved on surrogate endpoints, using this linkage. Precedent: registry-linked follow-up in Nordic and UK trials and in US cooperative-group studies via the National Death Index.","asOf":"2026-09-08","links":[{"label":"FDA Oncology Center of Excellence: Project Confirm","url":"https://www.fda.gov/about-fda/oncology-center-excellence/project-confirm"}],"tags":[],"related":["seer"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["os","accelerated-approval"],"trials":[],"people":[],"bottlenecks":["b-trial-design","b-real-world-evidence"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Registry-linked follow-up will deliver long-term OS for most surrogate-based approvals at under 1 percent of the original trial cost, and will identify approvals whose survival benefit was not sustained.","rationale":"Long-term follow-up in trials is expensive because it relies on site visits; registries collect the same outcome routinely. Accelerated approvals frequently lack mature OS years later.","test":"Retrospectively link participants of five completed surrogate-endpoint trials to registries (with consent provisions permitting) and report the incremental OS information obtained and its cost.","maturity":"early-clinical","actor":"regulator","cost":"small","horizonYears":2},{"id":"idea-bio2-perioperative-betablocker-nsaid","kind":"idea","name":"Cheap perioperative beta-blocker plus anti-inflammatory to blunt surgical stress","aka":[],"tldr":"The stress of an operation may help stray cancer cells survive and settle. A few days of two cheap old drugs around surgery might reduce that risk.","summary":"Propranolol plus a COX-2 inhibitor given for days around surgery reduced pro-metastatic molecular signatures in randomised biomarker trials in breast and colorectal cancer, and observational series suggest lower recurrence. No commercial sponsor exists because both drugs are generic, so a publicly funded pragmatic trial is the only route to an answer.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Metastasis is understood least and studied last): Dillekås et al., Are 90% of deaths from cancer caused by metastases? (Cancer Medicine 2019)","url":"https://doi.org/10.1002/cam4.2474"}],"tags":[],"related":[],"cancers":["colorectal","breast-hr-positive"],"sections":[],"technologies":["mrd-testing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["emt"],"terms":[],"trials":[],"people":[],"bottlenecks":["b-metastasis-biology","b-generic-repurposing"],"keyPapers":["paper-dillekas-cancer-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Five to eleven days of perioperative propranolol plus an NSAID improves three-year distant disease-free survival by an absolute 3-5% after resection of colorectal or breast cancer, without excess surgical complications.","rationale":"Catecholamine and prostaglandin signalling drive immune suppression, epithelial-mesenchymal transition and vascular permeability in the perioperative window. The intervention is short, cheap and already pre-validated in humans at the transcriptomic level.","test":"A registry-embedded pragmatic randomised trial of about 3,000 resections across national surgical networks, using day-28 ctDNA as an intermediate endpoint for an early signal.","maturity":"early-clinical","actor":"clinic","cost":"medium","horizonYears":6},{"id":"idea-bio2-antigen-presentation-triage","kind":"idea","name":"Check whether a tumour can still show itself to the immune system","aka":[],"tldr":"Some tumours have broken the machinery that displays their identity to immune cells. Those patients cannot benefit from most immunotherapy and should be routed elsewhere.","summary":"Loss of HLA heterozygosity, B2M mutation, JAK1/2 loss and antigen presentation machinery defects are recurrent mechanisms of primary and acquired checkpoint resistance, and each is detectable from sequencing of tumour and germline. Routine reporting of an antigen presentation integrity score would identify patients who should be routed to HLA-independent therapies such as antibody-drug conjugates, natural killer cell engagers or CAR products.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (No one can predict who responds to immunotherapy): Haslam & Prasad (JAMA Network Open 2019)","url":"https://doi.org/10.1001/jamanetworkopen.2019.2535"}],"tags":[],"related":["oncokb","genie"],"cancers":[],"sections":[],"technologies":["wes-wgs","cgp","checkpoint-inhibitor","t-cell-engager","adc"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["hla-a02-restriction","neoantigen","resistance"],"trials":[],"people":["charles-swanton","ton-schumacher"],"bottlenecks":["b-immunotherapy-response","b-resistance","b-biomarker-validation"],"keyPapers":["paper-haslam-jama-netw-open"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Patients with antigen presentation defects derive little or no benefit from checkpoint blockade, and prospectively routing them to HLA-independent therapy improves survival compared with standard checkpoint therapy.","rationale":"The mechanism is causally necessary for T-cell recognition, so the prediction is mechanistic rather than correlative. HLA loss of heterozygosity calling from standard sequencing data is already available in research pipelines and could be added to commercial reports at low cost.","test":"Add antigen presentation integrity calling to an existing sequencing pipeline, test the interaction with checkpoint benefit retrospectively in trial cohorts, then run a strategy trial in defect-positive patients.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":5},{"id":"idea-pdac-neoadjuvant-chemotherapy-for-all-resectable-disease","kind":"idea","name":"Chemotherapy before surgery for every resectable pancreatic cancer, settled by the two perioperative trials rather than assumed","aka":[],"tldr":"Giving chemotherapy before the operation is standard when the tumour is borderline operable, but for tumours that can be removed straight away two trials have failed to show it beats operating first. Two more, one Dutch and one American, are directly comparing chemotherapy before and after surgery with chemotherapy after alone; the proposal is to wait for them and to pool them.","summary":"PREOPANC (2020) missed its primary endpoint (16.0 versus 14.3 months) but raised R0 resection from 40 to 71 percent and showed a five-year benefit in 2022; ESPAC-5 and Alliance A021501 supported neoadjuvant treatment for borderline resectable disease. For resectable disease, NORPACT-1 (2024) did not favour neoadjuvant FOLFIRINOX over upfront surgery and PREOPANC-2 (2025, 375 patients) found neoadjuvant FOLFIRINOX no better than gemcitabine chemoradiotherapy (21.9 versus 21.3 months), with neither trial using the current adjuvant standard of six months of modified FOLFIRINOX as comparator. The argument for neoadjuvant treatment for all is that a third of patients never receive adjuvant chemotherapy after a Whipple operation and that early systemic treatment tests biology before a major operation; the argument against is that FOLFIRINOX before surgery delays or prevents the operation in patients who progress and that PRODIGE 24 already delivers a median of 53.5 months in those who get it. PREOPANC-3 (378 estimated, primary completion January 2027) and Alliance A021806 (358, December 2028) compare perioperative with adjuvant modified FOLFIRINOX and are the trials that can settle it; a pre-planned pooled analysis, with resection rate, R0 rate and receipt of all planned chemotherapy as secondary endpoints, would give the answer more power than either alone.","asOf":"2026-09-24","links":[{"label":"ClinicalTrials.gov NCT04927780","url":"https://clinicaltrials.gov/study/NCT04927780"},{"label":"ClinicalTrials.gov NCT04340141","url":"https://clinicaltrials.gov/study/NCT04340141"},{"label":"PREOPANC-2 (Lancet Oncol 2025)","url":"https://europepmc.org/article/MED/40945523"}],"tags":["pancreatic-evidence"],"related":["idea-ras-inhibitor-neoadjuvant-pdac","surgery-roadmap"],"cancers":["pancreatic","resectable-pdac","borderline-resectable-pdac"],"sections":[],"technologies":["cytotoxic-chemotherapy"],"targets":[],"drugs":["folfirinox"],"companies":[],"institutions":[],"pathways":[],"terms":["neoadjuvant-adjuvant","total-neoadjuvant-therapy","resectability","resection-margins"],"trials":["preopanc","prodige-24","espac-5"],"people":[],"bottlenecks":["b-trial-design","b-surgery-radiation-innovation"],"keyPapers":["paper-preopanc-preoperative-chemoradiotherapy-jco-2020","paper-preopanc-2-neoadjuvant-folfirinox-vs-chemoradiotherapy-lancet-oncol-2025","paper-norpact-1-neoadjuvant-folfirinox-labori-lancet-gastroenterol-hepatol-2024","paper-prodige-24-five-year-outcomes-jama-oncol-2022","paper-alliance-a021501-mfolfirinox-radiotherapy-borderline-resectable-jama-oncol-2022"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Perioperative modified FOLFIRINOX improves overall survival over adjuvant modified FOLFIRINOX in resectable pancreatic cancer by a hazard ratio of 0.75 or better, and the benefit is carried by patients who would otherwise not have completed adjuvant treatment.","rationale":"The comparator problem in NORPACT-1 and PREOPANC-2 is fixed in the two running trials; individual patient pooling across 736 patients gives power for the subgroup (borderline versus clearly resectable, CA 19-9 high versus low) that decides practice.","test":"PREOPANC-3 and Alliance A021806 readouts (2027 to 2029) with a pre-registered pooled individual patient analysis; secondary endpoints resection rate, R0 rate, proportion receiving all planned chemotherapy, quality of life.","maturity":"being-tested-at-scale","actor":"research","cost":"large","horizonYears":4},{"id":"idea-gbc-neoadjuvant-for-high-risk-incidental-cancer","kind":"idea","name":"Chemotherapy before the second operation for high-risk incidental gallbladder cancer","aka":[],"tldr":"Gallbladder cancers found by chance often come back within six months of the second operation, usually far from the gallbladder, which suggests the disease was already in the bloodstream. Two randomised trials are testing chemotherapy first; one closed small, the other reports in 2028.","summary":"Most recurrences after radical re-resection are distant and early (Varshney 2025). GAIN (Germany, three cycles of gemcitabine-cisplatin before and after surgery) closed in October 2024 with 68 of 333 planned patients; OPT-IN (ECOG-ACRIN, phase 2/3, 186 estimated) randomises T2 to T3 incidental cancer to perioperative or adjuvant chemotherapy with an estimated primary completion of July 2028. Neoadjuvant treatment also selects out patients who progress during chemotherapy and would not have benefited from a major operation. The regimen question has moved on: TOPAZ-1 makes gemcitabine-cisplatin-durvalumab the natural perioperative arm for the next trial.","asOf":"2026-09-24","links":[{"label":"Varshney et al.: neoadjuvant treatment for incidental gallbladder cancer, systematic review (Ann Hepatobiliary Pancreat Surg 2025)","url":"https://europepmc.org/article/MED/40064481"},{"label":"ClinicalTrials.gov NCT04559139","url":"https://clinicaltrials.gov/study/NCT04559139"},{"label":"ClinicalTrials.gov NCT03673072","url":"https://clinicaltrials.gov/study/NCT03673072"}],"tags":["gallbladder-evidence"],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":[],"targets":[],"drugs":["gemcitabine-cisplatin","durvalumab"],"companies":["ecog-acrin"],"institutions":["krankenhaus-nordwest"],"pathways":[],"terms":["incidental-gallbladder-cancer","neoadjuvant-adjuvant","radical-cholecystectomy"],"trials":["opt-in","gain-igbc","topaz-1"],"people":[],"bottlenecks":["b-trial-enrolment","b-trial-design"],"keyPapers":["paper-varshney-neoadjuvant-incidental-gallbladder-cancer-systematic-review-ahbps-2025","paper-gain-trial-protocol-bmc-cancer-2020"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"In T2b, T3 or node-positive incidental gallbladder cancer, three cycles of gemcitabine-cisplatin (with or without durvalumab) before re-resection improves three-year overall survival over re-resection followed by adjuvant therapy.","rationale":"Early distant recurrence argues for systemic treatment before a morbid operation; the approach is standard in gastric and pancreatic cancer.","test":"OPT-IN's readout (2028) for chemotherapy alone; a successor trial adding durvalumab to the perioperative arm, stratified by T2a/T2b and nodes, run through the national incidental cancer pathway.","maturity":"being-tested-at-scale","actor":"research","cost":"medium","horizonYears":4},{"id":"idea-chemo-free-hodgkin","kind":"idea","name":"Chemotherapy-free Hodgkin lymphoma: brentuximab + PD-1 in early stage","aka":[],"tldr":"For a cancer already cured in 90% of young people, the goal is curing without the chemotherapy and radiation that cause heart disease and second cancers decades later.","summary":"Classical Hodgkin lymphoma is already cured in most young people, so the aim of this idea is to cure early-stage disease without the chemotherapy and radiotherapy that cause heart disease and second cancers decades later. Brentuximab vedotin plus nivolumab hits the Reed-Sternberg cell through CD30 and its immune shield through PD-1 and PD-L1, and the doublet has produced high complete response rates in relapsed disease and as frontline induction in older patients in the SGN35-015 cohort. The hypothesis is that PET- or ctDNA-adapted brentuximab-nivolumab with minimal or no chemotherapy achieves high progression-free survival in stage I to II disease with fewer late effects than ABVD-based therapy. AHOD2131, run by the Children's Oncology Group, is testing this at an early clinical stage.","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT05675410: AHOD2131 (COG / NCTN)","url":"https://clinicaltrials.gov/study/NCT05675410"}],"tags":[],"related":[],"cancers":["hodgkin-lymphoma"],"sections":[],"technologies":["pet-adapted-therapy","checkpoint-inhibitor","adc","ctdna-lymphoma-monitoring"],"targets":[],"drugs":["brentuximab-vedotin","nivolumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["ahod2131"],"people":[],"bottlenecks":[],"keyPapers":["paper-brentuximab-vedotin-hodgkin-lymphoma-lancet-oncol-2016","paper-checkmate-205-nivolumab-rr-hodgkin-extended-follow-up-jco-2018","paper-brentuximab-vedotin-hodgkin-lymphoma-blood-2018"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"In early-stage classical Hodgkin lymphoma, PET/ctDNA-adapted brentuximab-nivolumab with minimal or no chemotherapy achieves 3-year PFS ≥90% with fewer late effects than ABVD-based therapy.","rationale":"Two non-cytotoxic mechanisms hit both the Reed-Sternberg cell (CD30) and its immune shield (PD-1/PD-L1); late toxicity of anthracyclines, alkylators and radiation dominates survivorship.","test":"AHOD2131 primary results; a follow-on trial substituting ctDNA for interim PET; 20-year late-effects registry.","maturity":"early-clinical"},{"id":"idea-gbc-typhoid-carrier-cholecystectomy-or-surveillance","kind":"idea","name":"Cholecystectomy or ultrasound surveillance for chronic typhoid carriers in endemic regions","aka":[],"tldr":"People who carry the typhoid bacterium in their gallbladder long term have about four times the usual risk of gallbladder cancer. Two meta-analyses suggest offering them gallbladder removal or regular scans; no programme has tried it.","summary":"Chronic Salmonella Typhi carriage carried a pooled odds ratio of 4.28 across 17 studies (Nagaraja and Eslick 2014) and a summary relative risk of 4.6 to 5.0 in the Chilean case-control study and meta-analysis (Koshiol 2016), with the gallbladder as the reservoir of carriage. The carrier state is diagnosable by stool culture or Vi serology and cholecystectomy is also the treatment for carriage itself. A pragmatic programme in a typhoid-endemic, gallbladder-cancer-endemic region (northern India) could randomise identified carriers to cholecystectomy or annual ultrasound and measure cancer incidence, with the added public health benefit of removing a transmission reservoir.","asOf":"2026-09-24","links":[{"label":"Nagaraja and Eslick: chronic S. Typhi carrier state and gallbladder cancer, meta-analysis (Aliment Pharmacol Ther 2014)","url":"https://europepmc.org/article/MED/24612190"},{"label":"Koshiol et al.: S. Typhi and gallbladder cancer, case-control and meta-analysis (Cancer Med 2016)","url":"https://europepmc.org/article/MED/27726295"}],"tags":["gallbladder-evidence"],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["prophylactic-cholecystectomy","screening","inflammation"],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption","b-global-access"],"keyPapers":["paper-nagaraja-eslick-typhi-carrier-gallbladder-cancer-meta-analysis-apt-2014","paper-koshiol-salmonella-typhi-gallbladder-cancer-cancer-med-2016"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Offering cholecystectomy to confirmed chronic S. Typhi carriers aged 40 to 65 in high-incidence districts will reduce gallbladder cancer incidence in that group by at least half over ten years compared with surveillance alone.","rationale":"A fourfold relative risk on a high baseline incidence gives an absolute risk large enough to justify an operation that also cures carriage.","test":"Two-arm pragmatic randomised trial (cholecystectomy vs annual ultrasound) in identified carriers, primary endpoint gallbladder cancer incidence at ten years, secondary endpoints typhoid transmission and surgical morbidity; a preceding screening study to establish carrier prevalence and Vi serology performance.","maturity":"speculative","actor":"policy","cost":"medium","horizonYears":8},{"id":"idea-acc-infusion-sparing-regimens","kind":"idea","name":"Choose regimens by infusion-chair hours, not just efficacy, where chairs are the constraint","aka":[],"tldr":"When a hospital's real limit is the number of chemotherapy chairs and nurses, guidelines should favour treatments given by mouth or in fewer, shorter visits, if they work about as well.","summary":"Guidelines optimise efficacy and toxicity assuming unlimited delivery capacity. In systems where the chair, nurse, or pharmacy is the constraint, a regimen that is marginally less effective but needs a third of the visits may cure more people because more people get treated at all. Oral capecitabine-based regimens, three-weekly rather than weekly schedules, subcutaneous formulations, and shorter adjuvant durations are candidates. The proposal is a resource-stratified guideline layer that explicitly trades chair-hours against outcome, and trials to fill the evidence gaps.","asOf":"2026-09-08","links":[{"label":"NCCN Harmonized Guidelines for Sub-Saharan Africa","url":"https://www.nccn.org/global/what-we-do/harmonized-guidelines"}],"tags":[],"related":["nccn"],"cancers":[],"sections":["chemotherapy"],"technologies":["cytotoxic-chemotherapy"],"targets":[],"drugs":["carboplatin","paclitaxel"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-global-access","b-care-fragmentation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"In capacity-limited systems, adopting infusion-sparing regimens for the five most common indications will increase the number of patients starting curative treatment within 60 days by at least 25% without a measurable fall in two-year survival.","rationale":"Population-level outcome is efficacy multiplied by coverage; the field measures the first and ignores the second. Resource-stratified guidelines (NCCN Harmonized Guidelines for Sub-Saharan Africa) exist but do not model capacity explicitly.","test":"A health-systems simulation of chair capacity in three hospitals, then a pragmatic switch study comparing coverage, time to treatment, and survival before and after regimen policy change.","maturity":"speculative","actor":"research","cost":"medium","horizonYears":4},{"id":"idea-bio2-ctc-clearance-go-nogo","kind":"idea","name":"Circulating tumour cell clearance as the phase 2 gate for anti-metastatic drugs","aka":[],"tldr":"Cancer cells travelling in the blood can be counted. If a drug clears them, that is an early sign it may stop spread, and it reads out in weeks rather than years.","summary":"CTC count is an established prognostic marker in metastatic breast, prostate and colorectal cancer, and CTC conversion from unfavourable to favourable has been used as a response measure in prostate cancer. Anti-metastatic mechanisms such as platelet cloaking, trap-mediated capture and cluster formation should show up as CTC and CTC-cluster clearance long before imaging changes. A standardised cluster readout would give small, cheap, fast phase 2 decisions.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Metastasis is understood least and studied last): Dillekås et al., Are 90% of deaths from cancer caused by metastases? (Cancer Medicine 2019)","url":"https://doi.org/10.1002/cam4.2474"}],"tags":[],"related":[],"cancers":["breast-hr-positive","prostate"],"sections":[],"technologies":["liquid-biopsy","mrd-testing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["ctdna","mrd"],"trials":[],"people":["klaus-pantel","caroline-dive"],"bottlenecks":["b-metastasis-biology","b-biomarker-validation"],"keyPapers":["paper-dillekas-cancer-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Failure to reduce CTC cluster burden by half at four weeks predicts absence of metastasis-free survival benefit with high negative predictive value, allowing most anti-metastatic candidates to be killed in trials of under 60 patients.","rationale":"Clusters rather than single cells carry most metastatic potential in mouse and human studies, and their abundance is dynamic and drug-responsive. Clearance-based go/no-go decisions already work in leukaemia through MRD and in prostate cancer through PSA and CTC conversion.","test":"Add a harmonised CTC and cluster assay to three ongoing perioperative or adjuvant trials, and test the association between four-week clearance and relapse; publish the assay and thresholds openly.","maturity":"early-clinical","actor":"industry","cost":"medium","horizonYears":4},{"id":"idea-bio2-cxcr2-neutrophil-blockade","kind":"idea","name":"Clear the suppressive neutrophils out of pancreatic tumours first","aka":[],"tldr":"Pancreatic tumours are packed with a type of white blood cell that shuts down the immune attack. Blocking the signal that recruits them may open the tumour to immunotherapy.","summary":"CXCR2-dependent recruitment of granulocytic myeloid-derived suppressor cells is a dominant immunosuppressive mechanism in pancreatic and some head and neck cancers, and CXCR2 inhibition plus checkpoint blockade improved survival in genetically engineered mouse models. Human trials of CXCR1/2 inhibitors with chemotherapy or checkpoint blockade have been small and biomarker-light. The decisive step is patient selection by neutrophil infiltration measured on tissue, not by blood counts alone.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Cold tumours and the immunosuppressive microenvironment): Haslam & Prasad, Estimation of the percentage of US patients eligible for and responding to checkpoint inhibitors (JAMA Netw Open 2019)","url":"https://doi.org/10.1001/jamanetworkopen.2019.2535"}],"tags":[],"related":[],"cancers":["pancreatic","head-and-neck"],"sections":[],"technologies":["checkpoint-inhibitor","digital-pathology-ai","single-cell-spatial"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["cold-vs-hot","desmoplasia"],"trials":[],"people":[],"bottlenecks":["b-tme-immunosuppression","b-immunotherapy-response"],"keyPapers":["paper-haslam-jama-netw-open"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"In tumours pre-selected for high granulocytic myeloid infiltration on baseline biopsy, CXCR2 blockade plus checkpoint therapy reduces intratumoural neutrophil density by half and produces objective responses in a population where checkpoint therapy alone gives almost none.","rationale":"The mechanism is one of the best supported in autochthonous pancreatic models, and the intervention is a small molecule with an established safety profile from inflammatory disease programmes.","test":"Biopsy-selected phase 2 with paired tissue myeloid quantification as primary endpoint and response as secondary; abandon if neutrophil density does not fall despite adequate exposure.","maturity":"early-clinical","actor":"industry","cost":"medium","horizonYears":6},{"id":"idea-bio1-senolytics-after-therapy","kind":"idea","name":"Clear the zombie cells left behind by chemotherapy and radiotherapy","aka":[],"tldr":"Treatment leaves behind damaged cells that stop dividing but do not die, and they release signals that help surviving cancer cells regrow. Removing them could reduce relapse.","summary":"Therapy-induced senescence produces a secretory phenotype that promotes proliferation, angiogenesis and immune suppression, and senescent tumour cells can re-enter the cell cycle. Senolytics such as navitoclax-class BCL-2 family inhibitors and dasatinib-quercetin combinations clear these cells in models, and a one-two sequence of pro-senescence therapy followed by a senolytic has shown benefit preclinically.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Acquired resistance to every therapy): Soria et al., Osimertinib in untreated EGFR-mutated NSCLC (FLAURA, NEJM 2018)","url":"https://doi.org/10.1056/NEJMoa1713137"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["cytotoxic-chemotherapy"],"targets":["bcl2"],"drugs":[],"companies":[],"institutions":[],"pathways":["apoptosis-bcl2"],"terms":[],"trials":[],"people":[],"bottlenecks":["b-resistance","b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A senolytic given after therapy-induced senescence reduces relapse rates in models and lowers markers of senescence and inflammation in patients after chemotherapy or radiotherapy.","rationale":"The sequence is mechanistically rational and both halves already exist clinically; senolytics are being tested in ageing and fibrosis, providing safety data.","test":"A window study measuring senescence markers in tumour and normal tissue before and after a short senolytic course following neoadjuvant chemotherapy, with residual disease as an exploratory endpoint.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":5},{"id":"idea-pv-clone-directed-therapy","kind":"idea","name":"Clearing the JAK2 clone in polycythaemia vera: interferon plus mutant-selective inhibitors as a route to treatment-free remission","aka":[],"tldr":"Today's PV drugs control blood counts but leave the mutant cells in place. Interferon is the one treatment that shrinks the clone, and the first JAK2 V617F-selective inhibitors have entered trials; combining the two could aim at molecular remission, the way imatinib did for CML.","summary":"Polycythaemia vera is driven by a single recurrent mutation in almost every patient, yet no treatment is given with the aim of eliminating it. Ropeginterferon alfa-2b lowers the JAK2 V617F allele burden year on year in PROUD-PV and CONTINUATION-PV, and a fraction of patients reach very low burdens. Ruxolitinib blocks wild-type and mutant JAK2 alike, which limits its dose and spares the clone. Mutant-selective JAK2 V617F inhibitors are now in first-in-human trials. The idea is to test interferon plus a mutant-selective inhibitor against interferon alone with molecular response and progression, not haematocrit, as the endpoints.","asOf":"2026-09-16","links":[],"tags":["polycythaemia-vera","mpn"],"related":[],"cancers":["polycythaemia-vera","myeloproliferative-neoplasms"],"sections":[],"technologies":["kinase-inhibitors"],"targets":["jak2"],"drugs":["ropeginterferon-alfa-2b","ruxolitinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["proud-pv","majic-pv"],"people":[],"bottlenecks":[],"keyPapers":["paper-jak2-polycythaemia-vera-lancet-2005","paper-jak2-polycythaemia-vera-nat-rev-cancer-2007","paper-jak2-myeloproliferative-neoplasms-leukemia-2010"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Ropeginterferon alfa-2b combined with a JAK2 V617F-selective inhibitor will produce deep molecular responses (allele burden below 1 percent) in a majority of patients within three years, and deep responders will have a lower rate of progression to myelofibrosis than count-controlled patients.","rationale":"Interferon's molecular responses are durable and associated with fewer events; complete responders in MAJIC-PV had better event-free survival; CML showed that a single-driver disease can be pushed to treatment-free remission once the clone is suppressed deeply enough.","test":"A randomised phase 2 in high-risk PV: ropeginterferon with or without a mutant-selective JAK2 inhibitor once phase 1 doses are set, with JAK2 V617F allele burden at 24 and 36 months as the primary endpoint and progression, thrombosis and treatment discontinuation as secondary endpoints.","maturity":"early-clinical","actor":"industry","cost":"large","horizonYears":7},{"id":"idea-tnbc-disparities-in-access-and-outcomes","kind":"idea","name":"Close the gap between who gets triple-negative breast cancer and who is in its trials","aka":[],"tldr":"Black women in the United States have about twice the odds of a triple-negative diagnosis and, in the UK POSH cohort, worse survival than White women despite equal chemotherapy use. The pivotal trials enrolled few of them. Enrolment targets tied to incidence, reported by ethnicity in every primary paper, would make the evidence match the disease.","summary":"The Carolina Breast Cancer Study found basal-like tumours in 39 percent of premenopausal African American women against 16 percent of others; the US Cancer Statistics analysis of 1.15 million cases gave non-Hispanic Black women an odds ratio of 2.27 for triple-negative diagnosis; California registry data showed five-year relative survival of 14 percent for Black women with late-stage disease. In the UK, POSH found 26.1 percent triple-negative disease in Black women under 41 against 18.6 percent in White women and five-year survival of 71.1 versus 82.4 percent with chemotherapy use equal at 89 percent, so access alone does not explain the gap. The pivotal immunotherapy and antibody-drug conjugate trials report ethnicity, where they report it, in single digits for Black participants. Whether biology (BRCA1 founder variants, subtype distribution, immune environment) or care (time to treatment, dose delivery, trial access) drives the outcome gap is unresolved because the data to separate them are not collected.","asOf":"2026-09-24","links":[{"label":"Scott et al.: triple-negative breast cancer disparities in the United States, 2010 to 2014 (Cancer 2019)","url":"https://europepmc.org/article/MED/31282032"},{"label":"Copson et al.: POSH, ethnicity and outcome in young UK breast cancer patients (Br J Cancer 2014)","url":"https://europepmc.org/article/MED/24149174"}],"tags":["tnbc-evidence"],"related":["idea-tnbc-uk-ethnicity-stratified-outcome-reporting"],"cancers":["tnbc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["germline-testing"],"trials":[],"people":[],"bottlenecks":["b-trial-diversity","b-global-access","b-care-fragmentation"],"keyPapers":["paper-carey-race-breast-cancer-subtypes-cbcs-jama-2006","paper-bauer-triple-negative-california-registry-cancer-2007","paper-scott-tnbc-disparities-uscs-cancer-2019","paper-copson-posh-ethnicity-young-breast-cancer-uk-bjc-2014","paper-howlader-us-incidence-breast-subtypes-jnci-2014"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Requiring phase 3 triple-negative breast cancer trials to set enrolment targets for Black and Hispanic participants proportional to incidence in the enrolling countries, and to report efficacy and toxicity by ethnicity in the primary publication, will within five years show whether treatment effects differ by ancestry and will halve the enrolment gap without slowing accrual.","rationale":"Under-representation means the drugs that now define standard care were tested largely in the population least affected; disparities in incidence are established and in outcome persist under equal access, so ancestry-stratified evidence is a scientific need as well as an equity one.","test":"Audit of ethnicity enrolment and reporting in every phase 3 triple-negative trial since 2015 as baseline; a regulator- or funder-mandated enrolment plan for new trials with pre-specified ancestry subgroups; a UK cohort linking ethnicity, germline status, subtype, treatment delivery and outcome through national registry and NHS data.","maturity":"speculative","actor":"policy","cost":"medium","horizonYears":5},{"id":"idea-reg-early-apheresis-banking","kind":"idea","name":"Collect and freeze T cells at diagnosis for high-risk patients, before chemotherapy","aka":[],"tldr":"By the time patients need CAR-T their immune cells are often exhausted by earlier treatment. Storing healthy cells early would improve manufacturing success and cut the wait.","summary":"Manufacturing failures and poor CAR-T fitness are associated with prior lines of chemotherapy, bendamustine exposure and low lymphocyte counts. Collecting and cryopreserving autologous lymphocytes at diagnosis or first relapse for patients with a high probability of later needing CAR-T (high-risk large B-cell lymphoma, high-risk myeloma) would supply fitter starting material and remove apheresis scheduling from the critical path. The proposal is a prospective banking programme with defined eligibility, consent and storage funding, and a regulatory position on the use of banked material.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Manufacturing cost and time for living and radioactive medicines): Hernandez, Prasad & Gellad, Total costs of chimeric antigen receptor T-cell immunotherapy (JAMA Oncology 2018)","url":"https://doi.org/10.1001/jamaoncol.2018.0977"}],"tags":[],"related":[],"cancers":["dlbcl","multiple-myeloma"],"sections":[],"technologies":["car-t"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-manufacturing-cell-therapy"],"keyPapers":["paper-hernandez-jama-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Patients treated from banked early-collected cells have a manufacturing failure rate below 3% (versus 5-15% from late apheresis), a shorter referral-to-infusion interval by at least ten days, and higher CAR-T expansion and durable response rates.","rationale":"T-cell fitness is the strongest product-level predictor of CAR-T outcome, and it declines with each line of therapy; banking is routine for stem cells in myeloma and the storage cost is modest relative to the therapy.","test":"Prospective cohort banking cells in 300 newly diagnosed high-risk lymphoma patients, comparing manufacturing metrics and outcomes for those later needing CAR-T against contemporaneous patients apheresed at relapse.","maturity":"early-clinical","actor":"clinic","cost":"medium","horizonYears":4},{"id":"idea-tr2-resistance-mechanism-baskets","kind":"idea","name":"Combination baskets defined by resistance mechanism rather than by cancer type","aka":[],"tldr":"Group patients by why their last drug stopped working, then test the combination designed to fix that specific failure, whatever the cancer.","summary":"Progression biopsies and ctDNA now reveal resistance mechanisms (SLFN11 loss for topoisomerase-1 payloads, MET amplification for EGFR inhibitors, RB loss for CDK4/6 inhibitors). A basket trial enrolling by mechanism would test the matched rescue combination (for example ATR inhibitor plus the same ADC for SLFN11-low tumours) across histologies, converting a resistance hypothesis into a trial in months.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Too many combinations to test): Palmer & Sorger, Combination cancer therapy can confer benefit via patient-to-patient variability without drug additivity or synergy (Cell 2017)","url":"https://doi.org/10.1016/j.cell.2017.11.009"}],"tags":[],"related":["idea-payload-switching","idea-tr2-smart-sequencing-adc"],"cancers":[],"sections":[],"technologies":["adc","cdk46-inhibitor"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["tumour-agnostic","efflux-pump"],"trials":[],"people":[],"bottlenecks":["b-combination-space","b-resistance"],"keyPapers":["paper-palmer-cell"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Mechanism-defined baskets will achieve objective response rates at least twice those of unselected post-progression combination cohorts of the same agents.","rationale":"Histology-agnostic approvals (NTRK, MSI-high) proved that biology can define a population; resistance mechanisms are the same idea applied after progression.","test":"A three-cohort basket: SLFN11-low after a TOP1 ADC, MET-amplified after EGFR TKI, and RB1-loss after CDK4/6 inhibitor, each with a pre-specified rescue combination and a Simon two-stage design.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":4},{"id":"idea-bio2-gdf15-plus-exercise","kind":"idea","name":"Combine the new anti-wasting antibody with exercise and protein","aka":[],"tldr":"A new antibody blocks the hormone that makes people with cancer lose appetite and weight. Weight regained as muscle, not fat, needs exercise and protein alongside it.","summary":"GDF-15 is a tumour-derived hormone acting on the brainstem GFRAL receptor to suppress appetite, and a randomised phase 2 of the anti-GDF-15 antibody ponsegromab reported weight gain and improved appetite in cancer cachexia. Weight gain alone is not the goal: without a resistance training and protein stimulus, regained mass is likely to be fat rather than functional muscle.","asOf":"2026-09-08","links":[{"label":"Cachexia (overview)","url":"https://en.wikipedia.org/wiki/Cachexia"}],"tags":[],"related":["idea-exercise-as-adjuvant"],"cancers":["pancreatic","nsclc","colorectal"],"sections":[],"technologies":["exercise-oncology","monoclonal-antibody"],"targets":[],"drugs":[],"companies":["pfizer"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-cachexia-supportive","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Anti-GDF-15 therapy combined with supervised resistance exercise and protein supplementation produces greater gains in lean mass and physical function than the antibody alone, at equal total weight gain.","rationale":"Anabolic signals are needed to direct nutrient partitioning into muscle, as shown by decades of sarcopenia and geriatric rehabilitation research. Function, not weight, is what determines whether patients can tolerate treatment and live independently.","test":"A factorial randomised trial of antibody with or without a structured exercise and nutrition programme, with lean mass by imaging and a physical function measure as co-primary endpoints.","maturity":"early-clinical","actor":"industry","cost":"medium","horizonYears":5},{"id":"idea-tr1-community-health-worker-recruitment","kind":"idea","name":"Community health workers and trusted local organisations paid to recruit for trials","aka":[],"tldr":"People join trials when someone they trust explains them. Paying community health workers, churches and local groups to inform and refer people would reach communities that hospitals do not.","summary":"Trial sponsors and networks contract community health workers and community organisations for outreach, education and referral in under-represented communities, with training in trial literacy and payment per activity rather than per enrolment (to avoid coercion). Evaluated in a cluster-randomised design against standard site-based recruitment.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Trials do not represent the people who get cancer): Loree et al., Disparity of race reporting and representation in trials leading to cancer drug approvals (JAMA Oncology 2019)","url":"https://doi.org/10.1001/jamaoncol.2019.1870"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["nci"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-diversity","b-trial-enrolment"],"keyPapers":["paper-loree-jama-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Communities with paid CHW outreach will contribute at least twice the enrolment of minority and low-income participants compared with matched communities without it, and enrolled participants will have retention equal to others.","rationale":"CHW models raised vaccination, screening and HIV testing uptake in similar communities; trial participation shares the same trust and information barriers.","test":"Cluster-randomise 20 community areas around trial sites to CHW outreach or none for 18 months, with enrolment by demographic as the primary outcome.","maturity":"early-clinical","actor":"philanthropy","cost":"medium","horizonYears":2},{"id":"idea-acc-community-health-workers-oncology","kind":"idea","name":"Community health workers trained in cancer triage, navigation and home palliative care","aka":[],"tldr":"Millions of community health workers already visit homes for vaccines and maternal care. Training them to recognise cancer warning signs, guide patients through the system and support home pain care would reach people no hospital does.","summary":"Community health worker programmes are the backbone of primary care in much of the world but rarely include cancer. A cancer module covering red-flag symptoms, referral, treatment adherence follow-up, and home palliative support (pain reassessment, morphine adherence, caregiver training) would connect the last mile to cancer services. Kerala's community palliative network and several African pilots show feasibility.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Not enough oncologists, nurses, pathologists, physicists): Yang et al., Projected supply of and demand for oncologists and radiation oncologists through 2025 (JOP 2014)","url":"https://doi.org/10.1200/JOP.2013.001319"}],"tags":[],"related":[],"cancers":["cervical","breast-hr-positive"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-workforce","b-palliative","b-global-access"],"keyPapers":["paper-yang-j-oncol-pract"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Catchments with cancer-trained community health workers will show earlier stage at diagnosis for breast and cervical cancer and higher rates of pain control at home compared with catchments with standard programmes.","rationale":"Community health workers have moved population outcomes for HIV, TB, and maternal health where they are supervised and supplied; cancer symptoms and palliative needs fit the same model.","test":"Cluster-randomised trial across 30 catchments with stage distribution, time from symptom to first contact, and home pain scores as endpoints.","maturity":"early-clinical","actor":"clinic","cost":"small","horizonYears":2},{"id":"idea-prev-oral-cancer-community-smartphone-ai","kind":"idea","name":"Community health workers with smartphone AI screen for mouth cancer in South Asia","aka":[],"tldr":"Mouth cancer is common where tobacco is chewed and is visible to the naked eye. Health workers with a phone camera and AI could find it early in villages.","summary":"Mouth cancer is common where tobacco is chewed and is visible to the naked eye, so this idea equips community health workers in South Asia with smartphone cameras and an AI second read, plus tele-referral, to screen high-incidence districts. The Kerala cluster RCT showed that visual oral screening saves lives in tobacco and alcohol users, and smartphone AI triage has shown promising accuracy in India, so the missing piece is scalable, low-cost delivery. The aim is to detect oral potentially malignant disorders and shift diagnosis towards stage I-II. The test is a stepped-wedge rollout across Indian districts with registry linkage and Tata Memorial Centre as a partner. At early-clinical maturity it addresses The hardest cancers are found late and Most of the world has almost no cancer care.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The hardest cancers are found late): Crosby et al., Early detection of cancer (Science 2022)","url":"https://doi.org/10.1126/science.aay9040"}],"tags":[],"related":[],"cancers":["head-and-neck"],"sections":["early-detection"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["tata-memorial"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-early-detection","b-global-access"],"keyPapers":["paper-crosby-science"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"AI-assisted community screening achieves at least 80% sensitivity for oral potentially malignant disorders and shifts stage distribution at diagnosis by at least 15 percentage points toward stage I-II.","rationale":"Mortality benefit is shown; the missing piece is scalable, low-cost delivery.","test":"Run a stepped-wedge rollout across districts in India with registry linkage.","maturity":"early-clinical","actor":"policy","cost":"medium","horizonYears":4},{"id":"idea-prev-pharmacy-prevention-hub","kind":"idea","name":"Community pharmacies as one-stop cancer prevention hubs","aka":[],"tldr":"Pharmacies are everywhere and open late. They could give HPV vaccines, hand out bowel test kits, run stop-smoking clinics and offer HPV self-sampling under one roof.","summary":"Pharmacies are everywhere and open late, so this idea commissions a bundled prevention service under one roof: HPV catch-up vaccination, FIT kit distribution, cervical self-sampling, cessation pharmacotherapy and alcohol brief advice, with performance payment. Pharmacies already deliver vaccination and cessation in many countries, and access and convenience are the main barriers for the least-served. The aim is higher screening and vaccination uptake in under-served areas. The test is a regional commissioning pilot by payers with matched control areas. At early-clinical maturity it addresses the bottlenecks Prevention we already have is not deployed and Not enough oncologists, nurses, pathologists, physicists.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Prevention we already have is not deployed): Islami et al., Proportion of cancer attributable to modifiable risk factors (CA 2018)","url":"https://doi.org/10.3322/caac.21440"}],"tags":[],"related":[],"cancers":[],"sections":["prevention"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption","b-workforce"],"keyPapers":["paper-islami-ca-cancer-j-clin"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Pharmacy hubs increase screening and vaccination uptake in under-served areas by at least 10 percentage points within three years.","rationale":"Access and convenience are the main barriers for the least-served; pharmacies solve both.","test":"Regional commissioning pilot with matched control areas.","maturity":"early-clinical","actor":"payer","cost":"medium","horizonYears":3},{"id":"idea-moon-hpv-vaccine-confidence","kind":"idea","name":"Community-tailored HPV vaccine confidence campaigns with school-based delivery","aka":[],"tldr":"The HPV vaccine prevents most cervical cancer, but false safety claims have cut uptake in several countries. Rebuild confidence locally and deliver the vaccine in schools.","summary":"HPV vaccination collapsed in Japan after unfounded safety concerns and has stalled in parts of Europe and the US; countries with school-based programmes and sustained trusted messaging (Australia, Scotland, Rwanda) achieve high coverage and are seeing dramatic falls in cervical disease. The proposal is a programme combining school-based single-dose delivery, community-specific confidence work through trusted messengers, and rapid response to local scares, with coverage tracked at district level.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Misinformation and unproven therapies): Johnson et al., Cancer misinformation and harmful information on Facebook and other social media (JNCI 2022)","url":"https://doi.org/10.1093/jnci/djab141"}],"tags":[],"related":[],"cancers":["cervical","head-and-neck"],"sections":[],"technologies":["hpv-vaccine"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-misinformation","b-prevention-adoption"],"keyPapers":["paper-johnson-j-natl-cancer-inst"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Tailored confidence campaigns with school delivery raise coverage above 80% in low-uptake districts within three years.","rationale":"Coverage differences between neighbouring countries with the same vaccine show that delivery model and trust, not biology, determine uptake.","test":"Cluster-randomised campaign rollout across low-uptake districts with coverage as the primary endpoint.","maturity":"being-tested-at-scale","actor":"policy","cost":"medium","horizonYears":3},{"id":"idea-moon-compact-flash-proton","kind":"idea","name":"Compact FLASH and proton systems at the price of a conventional linac","aka":[],"tldr":"Ultra-fast FLASH radiotherapy and proton beams may spare healthy tissue dramatically, but the machines cost tens of millions. Engineer versions that any hospital can afford.","summary":"FLASH radiotherapy (dose delivered in under a second) reduces normal tissue toxicity in animal models with preserved tumour control and has entered early human trials; proton therapy spares normal tissue by physics but costs an order of magnitude more than photon systems. Compact accelerator concepts (very-high-energy electrons, laser-driven and superconducting compact proton sources) could lower cost. The proposal is a focused engineering programme, with milestone funding, to deliver a compact system capable of FLASH-rate delivery at a capital cost comparable to a conventional linac, paired with the clinical trials needed to establish the FLASH effect in humans.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Surgery and radiotherapy cure most, get least): Sullivan et al., Global cancer surgery (Lancet Oncology Commission 2015)","url":"https://doi.org/10.1016/S1470-2045(15)00223-5"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["flash-rt","proton-therapy"],"targets":[],"drugs":[],"companies":["iba","mevion","varian"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-surgery-radiation-innovation","b-toxicity-qol"],"keyPapers":["paper-sullivan-lancet-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A compact system delivers FLASH-rate treatment at conventional linac cost within eight years, and randomised trials confirm reduced late toxicity at equal tumour control in at least one indication.","rationale":"Toxicity from radiotherapy limits dose and quality of life; if the FLASH effect holds in humans, cost is the only barrier to universal benefit, and accelerator physics is advancing quickly.","test":"Prototype within four years with dosimetric validation; first randomised FLASH versus conventional trial in a toxicity-limited indication such as head and neck or paediatric tumours.","maturity":"preclinical-evidence","actor":"industry","cost":"large","horizonYears":8},{"id":"idea-reg-comparability-by-design-digital-twin","kind":"idea","name":"Comparability by design: a digital twin and sentinel panel for cell process changes","aka":[],"tldr":"Improving how a cell therapy is made currently risks having to repeat clinical trials. A validated computer model plus a fixed set of product measurements would let changes be approved on data alone.","summary":"Because assays of how well a cell-therapy batch kills its target are imperfect, regulators often require clinical bridging when a cell-therapy process changes (new device, new site, shorter culture), freezing suboptimal processes. The proposal is a pre-agreed comparability framework: a mechanistic and statistical model of the process (a digital twin) validated against historical runs, a sentinel panel of product attributes (phenotype, transcriptomic signature, cytotoxicity, cytokine profile, vector copy number) with pre-specified equivalence margins, and a regulatory commitment to accept changes that fall within the margins without clinical data.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Manufacturing cost and time for living and radioactive medicines): Hernandez, Prasad & Gellad, Total costs of chimeric antigen receptor T-cell immunotherapy (JAMA Oncology 2018)","url":"https://doi.org/10.1001/jamaoncol.2018.0977"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["car-t","single-cell-spatial"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-manufacturing-cell-therapy","b-regulatory-fragmentation"],"keyPapers":["paper-hernandez-jama-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Under the framework, the median time to implement a major cell-therapy process change falls from more than two years to under six months, with no detectable change in clinical outcomes in the outcomes registry.","rationale":"Biosimilars established that analytical similarity within margins can replace clinical trials; cell therapies need richer attribute panels, but single-cell and transcriptomic characterisation now make such panels feasible.","test":"Retrospectively apply the sentinel panel to products that underwent process changes with known clinical outcomes to calibrate margins; then pilot the framework prospectively with two manufacturers and regulators.","maturity":"speculative","actor":"regulator","cost":"medium","horizonYears":4},{"id":"idea-tr1-shared-control-arms-across-sponsors","kind":"idea","name":"Competing sponsors share one control arm in the same indication","aka":[],"tldr":"Three companies testing three drugs against the same standard treatment each recruit their own control group. Pooling those controls in one shared study would need fewer patients and answer faster.","summary":"A neutral academic sponsor runs a master protocol in a defined indication with a single concurrent control arm; each company adds its experimental arm under a pre-agreed data-access and publication charter, paying a per-patient fee. Randomisation is concurrent, so this is a true RCT for each comparison. Precedents include the Lung-MAP and I-SPY structures, but industry-led registrational use is rare.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Trial design, endpoints and cost): Davis et al., Availability of evidence of benefits on survival and quality of life of cancer drugs approved by EMA 2009-13 (BMJ 2017)","url":"https://doi.org/10.1136/bmj.j4530"}],"tags":[],"related":[],"cancers":["nsclc","pancreatic"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["basket-umbrella-platform"],"trials":[],"people":[],"bottlenecks":["b-trial-design","b-trial-enrolment","b-ip-collaboration"],"keyPapers":["paper-davis-bmj"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A shared-control master protocol will reduce total patients randomised to control by more than half across participating programmes and produce registrational-quality comparisons acceptable to regulators.","rationale":"Control patients receive no experimental benefit and are the largest avoidable cost across a competitive indication. Regulators have signalled openness to master protocols for registration.","test":"Convene sponsors developing agents in one crowded first-line setting under an antitrust-cleared charter; run the shared-control protocol for one round of arms and compare efficiency with the sponsors' stand-alone plans.","maturity":"speculative","actor":"industry","cost":"medium","horizonYears":4},{"id":"idea-reg-conditional-approval-sunset","kind":"idea","name":"Conditional approvals that lapse automatically if the confirmatory trial is late","aka":[],"tldr":"Drugs given accelerated or conditional approval on surrogate endpoints have often stayed on the market for years after the confirmatory trial stalled or failed. The approval would lapse automatically if the sponsor missed agreed enrolment milestones or the readout date, unless an independent panel granted a documented extension.","summary":"Accelerated and conditional approvals have often stayed on the market for years after confirmatory trials stalled or failed (the 'dangling' approvals reviewed in 2021). The FDORA 2022 reforms gave FDA power to require confirmatory trials to be underway and to expedite withdrawal; the EU renews conditional authorisations annually. The proposal is a self-executing sunset: at approval, the sponsor agrees enrolment milestones and a readout date, and the authorisation lapses without further procedure if the milestones are missed, unless an independent panel grants a documented extension.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Regulatory divergence between regions): FDA Oncology Center of Excellence, Project Orbis","url":"https://www.fda.gov/about-fda/oncology-center-excellence/project-orbis"}],"tags":[],"related":["fda-approvals"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["accelerated-approval"],"trials":[],"people":[],"bottlenecks":["b-regulatory-fragmentation","b-incentive-misalignment"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Under an automatic sunset, the median time from accelerated approval to confirmatory readout falls below four years and the share of accelerated oncology indications still unconfirmed at five years falls below 10%, without a fall in the number of accelerated approvals granted.","rationale":"Sponsors currently face weak incentives to complete confirmatory trials quickly because the drug is already earning revenue. A credible, non-discretionary deadline shifts the incentive; regulators would no longer need to spend years negotiating voluntary withdrawals.","test":"Apply the sunset to all new accelerated oncology approvals in one jurisdiction for five years and compare time to confirmation and withdrawal rates with the previous five-year cohort.","maturity":"early-clinical","actor":"regulator","cost":"small","horizonYears":5},{"id":"idea-reg-olanzapine-cachexia-global-confirmation","kind":"idea","name":"Confirm low-dose olanzapine for appetite and weight in advanced cancer worldwide","aka":[],"tldr":"A randomised placebo-controlled trial at Tata Memorial found that 2.5 mg of olanzapine daily, a cheap antipsychotic pill already used for chemotherapy nausea, improved appetite and weight gain in patients starting chemotherapy for advanced stomach, lung and hepatopancreatobiliary cancers. A multinational confirmatory trial is needed before guidelines and labels adopt it.","summary":"A randomised placebo-controlled trial from Tata Memorial (published in the Journal of Clinical Oncology, 2023) found that 2.5 mg olanzapine daily improved weight gain and appetite in chemotherapy-naive patients with advanced gastric, lung and hepatopancreatobiliary cancers, an area where expensive investigational agents have repeatedly failed. Olanzapine costs cents and is already used for chemotherapy-induced nausea. The proposal is a multinational confirmatory trial with weight, appetite, quality of life and survival endpoints, coupled with a guideline and label strategy so the result reaches patients.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (No incentive to repurpose cheap drugs): Pantziarka et al., The Repurposing Drugs in Oncology (ReDO) Project (ecancer 2014)","url":"https://doi.org/10.3332/ecancer.2014.442"}],"tags":[],"related":[],"cancers":["gastric","nsclc","pancreatic"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["tata-memorial"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-generic-repurposing","b-cachexia-supportive"],"keyPapers":["paper-pantziarka-ecancermedicalscience"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Low-dose olanzapine increases the proportion of patients with advanced cancer gaining more than 5% body weight at 12 weeks by at least 20 absolute percentage points versus placebo, with improved appetite scores and no excess sedation.","rationale":"The initial trial effect was large and the drug's safety at 2.5 mg is well established; cachexia has no approved effective drug in most countries, and a generic solution would be adopted immediately if confirmed.","test":"Randomised placebo-controlled trial of about 500 patients across three continents with weight gain primary endpoint, followed by ESMO and ASCO guideline submissions.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":3},{"id":"idea-nl-antioxidant-supplement-harm-confirmation","kind":"idea","name":"Confirm or refute the harm of antioxidant supplements during chemotherapy","aka":[],"tldr":"Half of patients take antioxidant vitamins during chemotherapy. One good observational study suggests they raise recurrence by 40%. Patients deserve a definitive answer, and it can be obtained cheaply by adding supplement tracking to trials already running.","summary":"The DELCaP study nested in a breast cancer chemotherapy trial found that antioxidant supplements (vitamins A, C, E, carotenoids, coenzyme Q10) taken before and during chemotherapy were associated with a 41% higher recurrence and 40% higher mortality, with similar signals for vitamin B12, iron and omega-3. Randomised harm has been shown for beta-carotene in smokers and for antioxidants during head and neck radiotherapy. A randomised trial of antioxidants during chemotherapy is now ethically difficult; the pragmatic path is prospective supplement capture in every adjuvant trial and a pre-registered pooled analysis, plus a randomised trial of a stop-supplement counselling intervention.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Misinformation and unproven therapies): Johnson et al., Cancer misinformation and harmful information on Facebook and other social media (JNCI 2022)","url":"https://doi.org/10.1093/jnci/djab141"}],"tags":[],"related":["idea-moon-supplement-interaction-database"],"cancers":["breast-hr-positive","tnbc","colorectal","nsclc"],"sections":["nutrition-lifestyle","supportive-care"],"technologies":["dietary-supplements-treatment-interactions","cytotoxic-chemotherapy","nutrition-screening-mnt"],"targets":[],"drugs":["doxorubicin","paclitaxel"],"companies":[],"institutions":["mskcc"],"pathways":[],"terms":["unproven-diet-claims"],"trials":[],"people":[],"bottlenecks":["b-misinformation","b-real-world-evidence","b-toxicity-qol"],"keyPapers":["paper-johnson-j-natl-cancer-inst"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Prospectively recorded antioxidant supplement use during adjuvant chemotherapy is associated with worse disease-free survival across tumour types after adjustment, and a pharmacist-led counselling intervention at chemotherapy start reduces antioxidant use by half and is acceptable to patients.","rationale":"The mechanism (scavenging of the reactive oxygen species that mediate cytotoxic and radiation cell kill) is coherent, the observational signal is large, and the exposure is common, modifiable and almost never recorded. Patients currently receive contradictory advice from oncologists, pharmacies and the internet.","test":"Add a standardised supplement questionnaire to three ongoing adjuvant chemotherapy trials (breast, colorectal, lung) with a pre-registered pooled analysis; in parallel, a cluster-randomised trial of pharmacist supplement reconciliation and counselling at chemotherapy initiation with supplement cessation and patient satisfaction as endpoints.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":5},{"id":"idea-tr1-low-dose-immunotherapy-for-lmic","kind":"idea","name":"Confirm ultra-low-dose immunotherapy so it can be afforded where most patients live","aka":[],"tldr":"A single-centre trial at Tata Memorial found that adding nivolumab at about a twentieth of the usual dose to chemotherapy improved outcomes in head and neck cancer. Confirmatory trials against standard-dose immunotherapy are needed before low-dose labels could make immunotherapy affordable for millions.","summary":"Randomised confirmatory trials of low-dose PD-1 blockade (e.g., nivolumab 20 mg every three weeks, as tested at Tata Memorial in head and neck cancer with an OS benefit versus chemotherapy alone) in additional indications and against standard-dose immunotherapy, with PK and receptor-occupancy sub-studies, and a regulatory pathway for low-dose labels or guideline recommendations in resource-limited settings. Uncertainty is substantial: the evidence base is a single-centre trial and non-inferiority to full dose has not been shown.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Wrong doses): FDA Oncology Center of Excellence, Project Optimus","url":"https://www.fda.gov/about-fda/oncology-center-excellence/project-optimus"}],"tags":[],"related":[],"cancers":["head-and-neck","nsclc","cervical"],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":["pd1"],"drugs":["nivolumab"],"companies":[],"institutions":["tata-memorial"],"pathways":[],"terms":[],"trials":["checkmate-227","harmoni-3","keynote-024-189","keynote-042","keynote-a18"],"people":["patil-vijay","prabhash-kumar"],"bottlenecks":["b-dose-optimisation","b-global-access","b-drug-pricing"],"keyPapers":["paper-checkmate-017-nejm-2015"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Ultra-low-dose PD-1 blockade will show a survival benefit over chemotherapy alone in at least one further indication and will be within a pre-specified non-inferiority margin of standard dose in a direct comparison, at under 10 percent of the drug cost.","rationale":"Receptor occupancy and early PK studies suggest saturation at doses well below label; the Tata trial provides randomised clinical evidence, and the access gap is the largest single inequity in modern oncology.","test":"A multicentre randomised trial in India and one African network comparing low-dose nivolumab plus chemotherapy with chemotherapy alone in NSCLC or cervical cancer, plus a non-inferiority arm against standard dose where affordable.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":3},{"id":"idea-moon-continuous-ai-validation-registry","kind":"idea","name":"Continuous prospective validation for every oncology AI tool after deployment","aka":[],"tldr":"Cancer AI tools are approved on old test data and then never checked again. Require every deployed tool to report its real-world performance continuously, in public.","summary":"Radiology, pathology and prognostic AI tools in oncology are cleared on retrospective datasets; performance drifts with scanners, populations and practice, and post-market surveillance is minimal. The proposal is a regulatory requirement and shared infrastructure: every deployed oncology AI tool feeds outcome-linked performance metrics to a registry, stratified by site and demographic group, with public dashboards, drift alerts and pre-agreed thresholds for suspension, harmonised across regulators.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (AI that is built but not validated or deployed): Wu et al., How medical AI devices are evaluated: limitations and recommendations from an analysis of FDA approvals (Nature Medicine 2021)","url":"https://doi.org/10.1038/s41591-021-01312-x"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["radiology-ai-screening","digital-pathology-ai","pathology-foundation-model"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-ai-validation","b-regulatory-fragmentation"],"keyPapers":["paper-wu-nat-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Continuous validation detects clinically significant performance degradation in a meaningful share of deployed tools within two years and raises clinician trust and adoption of tools that perform well.","rationale":"Pharmacovigilance is standard for drugs; algorithms change performance more readily and silently, and a shared registry spreads the cost.","test":"Pilot registry across three tool categories in ten hospitals; measure detection of drift, time to corrective action, and comparison of registry performance with cleared claims.","maturity":"early-clinical","actor":"regulator","cost":"medium","horizonYears":3},{"id":"idea-reg-hpapi-continuous-flow","kind":"idea","name":"Continuous-flow synthesis of ultra-potent ADC payloads to ease the capacity squeeze","aka":[],"tldr":"The poisons carried by antibody-drug conjugates are so toxic that only a few factories can make them, and they are booked years ahead. Making them in small continuous reactors would ease the bottleneck.","summary":"Capacity to make the toxins carried by ADCs, such as exatecan derivatives, maytansinoids and auristatins, is concentrated in a small number of contract manufacturers with multi-year lead times, and handling these toxins in batches, even in milligram quantities, requires costly containment. Continuous-flow chemistry in enclosed micro- or meso-reactors reduces the inventory of toxic intermediates at any moment, shrinks containment footprint and allows numbering-up rather than scale-up. The proposal is a pre-competitive programme to develop and regulator-qualify flow routes for the three most used payload classes and license them openly to manufacturers.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Manufacturing cost and time for living and radioactive medicines): Hernandez, Prasad & Gellad, Total costs of chimeric antigen receptor T-cell immunotherapy (JAMA Oncology 2018)","url":"https://doi.org/10.1001/jamaoncol.2018.0977"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["adc"],"targets":[],"drugs":["trastuzumab-deruxtecan","enfortumab-vedotin"],"companies":[],"institutions":[],"pathways":[],"terms":["payload"],"trials":[],"people":[],"bottlenecks":["b-manufacturing-cell-therapy"],"keyPapers":["paper-hernandez-jama-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Qualified flow routes cut the cost of goods of payload-linker per gram by at least a third and reduce contract lead times for new ADC programmes from over 18 months to under nine.","rationale":"Continuous manufacturing is already accepted by FDA and EMA for several small molecules and is well suited to hazardous chemistry; the payload chemistries are known and the constraint is capital and containment, both of which flow reduces.","test":"Fund two academic-industrial groups to demonstrate GMP-grade flow synthesis of exatecan and MMAE at 100-gram scale, with regulator engagement on the control strategy, and publish cost and lead-time comparisons.","maturity":"preclinical-evidence","actor":"engineering","cost":"medium","horizonYears":3},{"id":"idea-nl-upf-controlled-feeding-trial","kind":"idea","name":"Controlled feeding trials to separate ultra-processing from calories","aka":[],"tldr":"We do not know whether ultra-processed food raises cancer risk because it makes people fat, or because of something in the food itself. Feeding volunteers matched diets for a few weeks and measuring cancer-relevant biology can tell the two apart.","summary":"The NIH inpatient trial by Hall (2019) showed people ate about 500 kcal/day more on an ultra-processed diet matched for macronutrients, supporting the adiposity route. Whether additives, emulsifiers, nitrites, sweeteners and packaging chemicals have direct effects on the gut microbiome, inflammation and DNA damage independent of energy intake is untested in humans. Controlled feeding with cancer-relevant intermediate endpoints is the only way to answer it before cohorts with 20-year follow-up mature, and it informs whether policy should target processing per se or energy density.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Prevention we already have is not deployed): Islami et al., Proportion of cancer attributable to modifiable risk factors (CA 2018)","url":"https://doi.org/10.3322/caac.21440"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":["nutrition-lifestyle","prevention"],"technologies":["ultra-processed-food-ssb","red-processed-meat-reduction","dietary-fibre-microbiome-io"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["ultra-processed-food","gut-microbiome-diversity","glycaemic-index"],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption","b-misinformation"],"keyPapers":["paper-islami-ca-cancer-j-clin"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"An ultra-processed diet matched for energy, macronutrients, fibre and weight change to a minimally processed diet produces measurable adverse changes in gut microbiome diversity, faecal genotoxicity, systemic inflammation and insulin over four weeks, indicating mechanisms beyond adiposity.","rationale":"Cohorts cannot disentangle processing from energy intake; mechanistic feeding trials in humans are feasible, affordable and have precedent (Hall 2019). Results would sharpen or refute the case for UPF-specific regulation.","test":"Randomised crossover feeding study (n about 60) with domiciled or fully provided diets, weight-stable design, endpoints including shotgun metagenomics, faecal water genotoxicity assays, CRP, IL-6, HOMA-IR and colonic biopsy proliferation markers in a subset.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":4},{"id":"idea-cost-managed-access-everywhere","kind":"idea","name":"Copy the Cancer Drugs Fund: pay for uncertain drugs while collecting the data","aka":[],"tldr":"Since 2016 England's Cancer Drugs Fund has paid a confidential discounted price for cancer drugs whose benefit is plausible but unproven, collected outcome data for two or three years, then had NICE decide for good; most drugs that entered were later recommended. Other systems could use the same managed-access deal instead of a yes-or-no at launch.","summary":"Since July 2016 England's Cancer Drugs Fund has operated as a managed-access scheme: NICE identifies drugs with plausible but uncertain benefit, NHS England pays a confidential discounted price under a fixed budget with an expenditure-control mechanism, and Public Health England collects outcome data; NICE then reappraises. Most drugs that entered have since been recommended for routine use. The model gives patients early access and gives the payer leverage and evidence. Germany's AMNOG, Canada's time-limited recommendations and Medicare's coverage with evidence development are partial versions.","asOf":"2026-09-10","links":[{"label":"NHS England: Cancer Drugs Fund","url":"https://www.england.nhs.uk/cancer/cdf/"},{"label":"OnCo: What the NHS offers","url":"https://onco-umber.vercel.app/coverage/uk/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["nice","g-ba-iqwig","pbac"],"pathways":[],"terms":["real-world-evidence"],"trials":[],"people":[],"bottlenecks":["b-drug-pricing","b-real-world-evidence","b-regulatory-fragmentation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Managed-access schemes with a fixed budget and mandatory data collection will deliver access one to two years earlier than standard appraisal at net prices at least 20% below list, with fewer than one in five drugs later withdrawn.","rationale":"The English scheme has published its outcomes; the mechanism is transferable to any single payer or large insurer.","test":"Adoption by two further systems with comparison of time to access, net price, evidence generated and final decisions against their prior process.","maturity":"being-tested-at-scale","actor":"policy","cost":"medium","horizonYears":3},{"id":"idea-fund-radiotherapy-trials-infrastructure","kind":"idea","name":"Core-funded radiotherapy trials infrastructure with central quality assurance","aka":[],"tldr":"Radiotherapy trials need physicists to check every plan and central review of every target drawn, which nobody pays for. Fund that infrastructure permanently so trials are faster and results are trustworthy.","summary":"A national or international radiotherapy trials infrastructure providing centralised contouring review, plan quality assurance, dosimetry audit, imaging and outcome data platforms and statistical support to academic radiotherapy trials, with core funding rather than per-trial grants. The UK's RTTQA group and CTRad, NRG's IROC and EORTC's RTQA show the model; their capacity limits how many trials can run. Quality assurance is the difference between radiotherapy trials that change practice (CHHiP, PACE, FAST-Forward) and those that fail from protocol deviation, which has measurably worsened outcomes in several past trials.","asOf":"2026-09-08","links":[{"label":"NRG Oncology","url":"https://www.nrgoncology.org/"},{"label":"ESTRO","url":"https://www.estro.org/"}],"tags":[],"related":["idea-fund-non-drug-trial-quota","idea-fund-flash-evidence-programme","idea-fund-course-based-radiotherapy-payment"],"cancers":[],"sections":[],"technologies":["imrt-igrt","sbrt","mr-linac"],"targets":[],"drugs":[],"companies":["nrg-oncology"],"institutions":["the-christie","icr-london","heidelberg-nct"],"pathways":[],"terms":[],"trials":[],"people":["uwe-oelfke","michael-baumann","ananya-choudhury"],"bottlenecks":["b-surgery-radiation-innovation","b-trial-design"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Core-funded QA infrastructure doubles the number of randomised radiotherapy trials opening per year in participating countries and reduces major protocol deviations to under 5% of plans, with trials reaching target accrual on time in most cases.","rationale":"The TROG 02.02 head and neck trial showed that poor plan quality erased the treatment effect; conversely, hypofractionation trials with strong QA changed global practice within a few years of publication. Radiotherapy has produced some of the highest-value trials in oncology per dollar; the constraint is infrastructure capacity.","test":"Fund infrastructure for one country for four years with throughput targets; compare trials opened, deviation rates and time to accrual with the preceding four years.","maturity":"being-tested-at-scale","actor":"policy","cost":"large","horizonYears":4},{"id":"idea-tr2-tenure-replication-credit","kind":"idea","name":"Count replications and open data in hiring and promotion","aka":[],"tldr":"Scientists are promoted for first-time discoveries and journal prestige, not for replicating others' work or sharing data. A structured section in tenure and promotion dossiers for replications conducted, data and code shared, and registered reports, weighted explicitly in decisions, would change what scientists spend their time on.","summary":"Career incentives drive the reproducibility problem: novelty and journal prestige are rewarded, replication and data sharing are not. Institutions signing DORA have pledged to reduce reliance on journal metrics. A concrete step is a structured section in tenure and promotion dossiers for replication studies conducted, data and code shared, registered reports and independent verification of one's own findings, weighted explicitly in decisions.","asOf":"2026-09-08","links":[{"label":"DORA","url":"https://sfdora.org/"}],"tags":[],"related":["idea-tr2-replication-set-aside"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-reproducibility","b-incentive-misalignment"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Institutions adopting the credit will see a doubling of replication studies and data deposits by their faculty within five years relative to matched institutions.","rationale":"Behaviour follows incentives; the shift to open data in genomics followed funder and institutional requirements, not exhortation.","test":"Five cancer centres adopt the dossier section; track faculty replication and sharing outputs against matched centres.","maturity":"speculative","actor":"policy","cost":"small","horizonYears":5},{"id":"idea-bio1-pan-ras-covalent-g12d","kind":"idea","name":"Covalent chemistry for the RAS mutations that still have no drug","aka":[],"tldr":"One RAS mutation can now be drugged because it offers a reactive handle. Most RAS mutations do not, so new chemistry is needed to grab other amino acids.","summary":"KRAS G12C inhibitors work by covalently modifying a cysteine. G12D, G12V and G13D, which together account for most RAS-driven cancer, lack that cysteine. Aspartate-targeting and lysine-targeting covalent chemistries, non-covalent tri-complex RAS(ON) inhibitors and pan-RAS agents are all in early clinical development. The proposal is a focused public-private chemistry programme on non-cysteine covalent warheads with tolerable reactivity, plus open sharing of failed warhead chemotypes.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The undruggable drivers): Dang et al., Drugging the 'undruggable' cancer targets (Nature Reviews Cancer 2017)","url":"https://doi.org/10.1038/nrc.2017.36"}],"tags":[],"related":[],"cancers":["pancreatic","colorectal"],"sections":[],"technologies":["kras-inhibitors"],"targets":["kras"],"drugs":["sotorasib","adagrasib","daraxonrasib"],"companies":["revolution-medicines","frontier-medicines","quanta-therapeutics"],"institutions":[],"pathways":[],"terms":[],"trials":["codebreak-300","nct07252232","nct07491445","nct07621718","rasolute-302"],"people":[],"bottlenecks":["b-undruggable-targets"],"keyPapers":["paper-dang-nat-rev-cancer","paper-kras-colorectal-j-clin-oncol-2008","paper-kras-colorectal-j-clin-oncol-2011","paper-kras-colorectal-j-clin-oncol-2010"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A non-cysteine covalent warhead class can achieve selective, durable engagement of KRAS G12D in vivo with acceptable off-target proteome reactivity, giving deeper responses than reversible binders.","rationale":"Covalency solves the picomolar-affinity requirement created by RAS's high GTP affinity; the G12C precedent shows that irreversible engagement translates into clinical activity.","test":"Chemoproteomic profiling of candidate warheads across the reactive proteome, then in vivo pharmacodynamics in KRAS G12D pancreatic and colorectal models against a benchmark RAS(ON) inhibitor.","maturity":"early-clinical","actor":"industry","cost":"large","horizonYears":5},{"id":"idea-fund-adaptive-radiotherapy-evidence","kind":"idea","name":"Coverage-with-evidence registries for MR-guided and adaptive radiotherapy","aka":[],"tldr":"Radiotherapy machines that adapt to the tumour each day cost far more than standard ones and their benefit is unproven. Payers would fund them only within registries and trials that measure whether they help.","summary":"Payers reimburse MR-linac and daily adaptive radiotherapy at a premium only for patients enrolled in an international registry with standard outcome and toxicity capture (building on the MR-Linac Consortium's MOMENTUM study) or in randomised comparisons for indications where a benefit is plausible (pancreatic, prostate, oligometastatic, bladder). The registry has pre-specified analysis plans and triggers for randomised trials. Adaptive radiotherapy has strong dosimetric rationale but the clinical benefit over conventional image-guided radiotherapy is unquantified, and the technology is diffusing on the strength of physics rather than outcomes.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Surgery and radiotherapy cure most, get least): Sullivan et al., Global cancer surgery (Lancet Oncology Commission 2015)","url":"https://doi.org/10.1016/S1470-2045(15)00223-5"}],"tags":[],"related":["idea-fund-proton-coverage-with-evidence","idea-fund-surgical-ai-robotics-evaluation"],"cancers":["pancreatic","prostate","urothelial"],"sections":[],"technologies":["mr-linac","imrt-igrt","sbrt"],"targets":[],"drugs":[],"companies":["elekta","varian","reflexion"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-surgery-radiation-innovation","b-real-world-evidence"],"keyPapers":["paper-sullivan-lancet-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Coverage-with-evidence generates outcome and toxicity data on more than 90% of adaptive radiotherapy patients in participating systems and produces at least two randomised comparisons with definitive results within five years.","rationale":"MOMENTUM has shown that an international MR-linac registry is feasible; the proton experience shows what happens without payment leverage. Adaptive radiotherapy is the next expensive technology where evidence should precede diffusion.","test":"Implement the conditional payment in two health systems and compare registry completeness and trial launch against systems reimbursing unconditionally.","maturity":"being-tested-at-scale","actor":"payer","cost":"medium","horizonYears":4},{"id":"idea-acc-diaspora-tele-tumour-boards","kind":"idea","name":"Credentialed diaspora oncologists staffing remote tumour boards for home-country hospitals","aka":[],"tldr":"Thousands of oncologists trained in poorer countries now work abroad. A structured programme could let them join weekly video case conferences for hospitals back home, improving decisions at almost no cost.","summary":"Ad hoc tele-tumour boards between high-income and LMIC centres exist but are fragile and unmeasured. A formal programme would credential diaspora and partner specialists, schedule weekly boards by tumour type, use a standard case template, record recommendations, and audit whether they were implemented and whether outcomes changed. The cost is coordination, not salaries.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Most of the world has almost no cancer care): WHO fact sheet, Cancer","url":"https://www.who.int/news-room/fact-sheets/detail/cancer"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-global-access","b-workforce","b-knowledge-diffusion"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Hospitals with a weekly structured remote tumour board will change management in at least 25% of presented cases and increase guideline-concordant treatment by at least 20 percentage points over one year.","rationale":"Multidisciplinary review changes management in a substantial minority of cases in every setting studied; the marginal value is highest where local specialist input is scarcest.","test":"Twelve hospitals, six with boards and six waitlisted, comparing concordance, time to treatment decision, and clinician-reported confidence.","maturity":"early-clinical","actor":"clinic","cost":"small","horizonYears":1},{"id":"idea-tnbc-ctdna-guided-adjuvant-decisions","kind":"idea","name":"ctDNA-guided adjuvant decisions after residual disease: escalate the positive, spare the negative","aka":[],"tldr":"After pre-surgery chemotherapy leaves tumour behind, a blood test for tumour DNA triples the risk of distant relapse when positive. The one trial that acted on it found the DNA usually appeared too late. A trial that tests at surgery with a tumour-informed assay, escalates positives to an antibody-drug conjugate and observes negatives has not been run.","summary":"In BRE12-158 ctDNA detected after neoadjuvant chemotherapy carried a distant disease-free survival hazard ratio of 2.99 and an overall survival hazard ratio of 4.16, and two-year distant disease-free survival was 56 versus 81 percent. c-TRAK TN tracked one or two mutations by digital PCR every three months: 27 percent turned positive within a year but 72 percent of those already had metastases and none of five given pembrolizumab cleared. The residual disease trials now running (ASCENT-05, TROPION-Breast03) enrol on residual cancer burden alone and treat everyone; the residual cancer burden pooled analysis shows RCB-I patients have ten-year relapse-free survival of 81 percent and may be over-treated, while RCB-III patients relapse in three quarters of cases and may need more than one agent. Tumour-informed assays and a first sample at surgery are the design changes c-TRAK TN's authors called for.","asOf":"2026-09-24","links":[{"label":"Radovich et al.: ctDNA and circulating tumour cells after neoadjuvant chemotherapy, BRE12-158 (JAMA Oncol 2020)","url":"https://europepmc.org/article/MED/32644110"},{"label":"c-TRAK TN (Ann Oncol 2023)","url":"https://europepmc.org/article/MED/36423745"},{"label":"ClinicalTrials.gov NCT05633654","url":"https://clinicaltrials.gov/study/NCT05633654"},{"label":"ClinicalTrials.gov NCT05629585","url":"https://clinicaltrials.gov/study/NCT05629585"}],"tags":["tnbc-evidence"],"related":["ctdna-tests"],"cancers":["tnbc"],"sections":[],"technologies":["liquid-biopsy","mrd-testing","adc"],"targets":[],"drugs":["sacituzumab-govitecan","datopotamab-deruxtecan","capecitabine","pembrolizumab","signatera"],"companies":[],"institutions":[],"pathways":[],"terms":["ctdna","mrd","rcb","neoadjuvant-adjuvant"],"trials":["ascent-05","tropion-breast03","keynote-522"],"people":[],"bottlenecks":["b-dormancy-mrd","b-biomarker-validation","b-trial-design"],"keyPapers":["paper-radovich-ctdna-ctc-bre12-158-jama-oncol-2020","paper-turner-c-trak-tn-ctdna-pembrolizumab-ann-oncol-2023","paper-symmans-rcb-long-term-prognosis-subtype-jco-2017","paper-yau-rcb-pooled-analysis-5161-lancet-oncol-2022","paper-create-x-adjuvant-capecitabine-nejm-2017"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Among patients with residual cancer burden II or III after chemotherapy plus pembrolizumab, a tumour-informed ctDNA test at surgery and at three months identifies a positive group in whom adding a TROP2 antibody-drug conjugate to standard post-neoadjuvant therapy improves three-year distant recurrence-free survival by at least 15 percentage points, and a persistently negative group in whom standard therapy alone yields three-year distant recurrence-free survival above 85 percent.","rationale":"Residual cancer burden is prognostic but coarse; ctDNA adds a dynamic measure of whether disease persists after surgery, and the antibody-drug conjugates now have first-line activity strong enough to clear micrometastatic disease that pembrolizumab alone did not.","test":"A two-cohort randomised trial nested in the post-neoadjuvant pathway: ctDNA-positive patients randomised to standard care with or without an antibody-drug conjugate; ctDNA-negative RCB-II patients randomised to standard care or observation; about 800 patients over four years, with ctDNA clearance at six months as an early endpoint.","maturity":"early-clinical","actor":"research","cost":"large","horizonYears":6},{"id":"idea-ctdna-guided-adjuvant-crc","kind":"idea","name":"ctDNA-guided adjuvant therapy as the default in stage II-III colon cancer","aka":[],"tldr":"Use a blood test after surgery to decide who gets chemotherapy: spare the negatives, and find something that actually works for the positives.","summary":"The idea is to make a post-operative ctDNA test such as Signatera the default decision tool for adjuvant therapy in stage II to III colon cancer, sparing ctDNA-negative patients chemotherapy and escalating positives to FOLFOX with or without a biology-matched agent. DYNAMIC showed that ctDNA-negative stage II patients can safely omit chemotherapy, while ALTAIR within CIRCULATE-Japan showed that late-line trifluridine and tipiracil does not help positives. The rationale is that post-operative ctDNA predicts recurrence far more strongly than any clinicopathological feature. Being tested at scale in CIRCULATE-US and COBRA-style platforms, it addresses the bottlenecks of dormant cells and minimal residual disease and of metastasis being studied last.","asOf":"2026-09-07","links":[{"label":"DYNAMIC: a blood test safely halved chemotherapy use after surgery for stage II colon cancer (New England Journal of Medicine 2022)","url":"https://doi.org/10.1056/NEJMoa2200075"},{"label":"GALAXY: tumour DNA in blood four weeks after bowel cancer surgery predicts relapse tenfold (Nature Medicine 2023)","url":"https://doi.org/10.1038/s41591-022-02115-4"}],"tags":[],"related":["colorectal-roadmap","idea-crc-ctdna-de-escalation-beyond-stage-ii"],"cancers":["colorectal"],"sections":[],"technologies":["mrd-testing"],"targets":[],"drugs":["signatera","folfox"],"companies":[],"institutions":[],"pathways":[],"terms":["mrd"],"trials":["dynamic","circulate-japan"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A ctDNA-directed strategy (omit in negatives; escalate positives with FOLFOX ± a biology-matched agent) yields non-inferior 3-year DFS with half the chemotherapy exposure across stage II-III.","rationale":"Post-operative ctDNA has a hazard ratio for recurrence near 10 and outperforms every clinicopathologic feature.","test":"CIRCULATE-US / NRG-GI005 (COBRA) style randomised platform with pre-specified escalation arms; DFS primary endpoint.","maturity":"being-tested-at-scale"},{"id":"idea-ctdna-guided-adjuvant-melanoma","kind":"idea","name":"ctDNA-guided adjuvant therapy in stage II-III melanoma","aka":[],"tldr":"Most stage II patients never relapse, yet all are offered a year of immunotherapy. Use a blood test to treat only those with detectable residual disease.","summary":"The idea is to reserve adjuvant PD-1 therapy in stage II to III melanoma for patients with detectable residual disease on a tumour-informed ctDNA assay, or to start it when ctDNA appears, instead of treating everyone. KEYNOTE-716 and CheckMate 76K treat all stage IIB and IIC patients for a modest absolute benefit although most never relapse, so over-treatment and immune toxicity are substantial. Melanoma sheds ctDNA in proportion to burden, and IMvigor011 proved the concept of ctDNA-triggered adjuvant immunotherapy in bladder cancer. The hypothesis is equivalent distant metastasis-free survival with far fewer patients treated; the test is the UK DETECTION design of ctDNA-triggered versus standard adjuvant pembrolizumab, addressing the dormancy bottleneck.","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT03553836: KEYNOTE-716","url":"https://clinicaltrials.gov/study/NCT03553836"},{"label":"ClinicalTrials.gov NCT04660344: IMvigor011","url":"https://clinicaltrials.gov/study/NCT04660344"}],"tags":[],"related":[],"cancers":["melanoma"],"sections":[],"technologies":["mrd-testing","checkpoint-inhibitor"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["mrd"],"trials":["keynote-716","imvigor011"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Reserving adjuvant PD-1 for ctDNA-positive patients (or starting at ctDNA conversion) achieves equivalent distant metastasis-free survival with far fewer patients treated.","rationale":"Melanoma sheds ctDNA proportional to burden; IMvigor011 proved the concept in bladder cancer; over-treatment and immune toxicity in stage II are substantial.","test":"Randomised trial of ctDNA-triggered versus standard adjuvant pembrolizumab in stage IIB-IIIA with DMFS endpoint (the DETECTION design).","maturity":"early-clinical"},{"id":"idea-bio1-ctdna-adaptive-tki","kind":"idea","name":"ctDNA-guided dose holidays for lung cancer targeted therapy","aka":[],"tldr":"Use tumour DNA in the blood as the signal to pause and restart a lung cancer pill, keeping the tumour in check while slowing the rise of resistant cells.","summary":"Adaptive therapy needs a fast, quantitative burden marker. In EGFR- and ALK-driven lung cancer, ctDNA falls to undetectable within weeks of TKI and rises before scans show progression. The proposal is a rules-based algorithm: pause the TKI when ctDNA has been undetectable for two consecutive draws, restart at reappearance, and compare with continuous dosing.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Tumour heterogeneity and clonal evolution): Gerlinger et al., Intratumor heterogeneity and branched evolution (NEJM 2012)","url":"https://doi.org/10.1056/NEJMoa1113205"}],"tags":[],"related":[],"cancers":["nsclc"],"sections":[],"technologies":["liquid-biopsy","kinase-inhibitors"],"targets":["egfr"],"drugs":["osimertinib"],"companies":[],"institutions":[],"pathways":[],"terms":["ctdna"],"trials":[],"people":[],"bottlenecks":["b-tumor-heterogeneity","b-resistance","b-dose-optimisation"],"keyPapers":["paper-flaura-nejm-2018","paper-egfr-nsclc-lancet-oncol-2012","paper-egfr-nsclc-n-engl-j-med-2010"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"ctDNA-guided intermittent osimertinib yields non-inferior progression-free survival to continuous dosing with fewer resistance mutations at progression and lower cumulative toxicity and cost.","rationale":"Intermittent dosing delayed resistance in BRAF melanoma models by exploiting drug-addiction of resistant cells; ctDNA provides the missing real-time burden signal for tumours that do not have a serum marker.","test":"Randomised phase 2 of 150 patients with EGFR-mutant NSCLC in deep molecular response on osimertinib: ctDNA-guided intermittent versus continuous; endpoints PFS, mechanism spectrum at progression, drug-free months.","maturity":"speculative","actor":"clinic","cost":"medium","horizonYears":4},{"id":"idea-ctdna-guided-parp-duration","kind":"idea","name":"ctDNA-guided duration of PARP maintenance","aka":[],"tldr":"Stop PARP inhibitors early in women whose blood shows no residual tumour DNA, and extend or switch in those whose ctDNA persists or reverts BRCA.","summary":"The two-year duration of olaparib maintenance in SOLO-1 and the three-year duration of niraparib in PRIMA were set by trial design rather than biology, so this idea proposes letting serial ctDNA decide how long each woman with ovarian cancer stays on a PARP inhibitor. Patients who are ctDNA-negative at twelve months would stop, while those with persistent ctDNA or a BRCA reversion mutation in plasma would switch to an ATR or POLQ inhibitor before radiographic progression. The rationale is that MRD-guided de-escalation has been shown in DYNAMIC and IMvigor011, and that BRCA reversion, the main resistance mechanism, is detectable in blood months before imaging relapse. The proposed test is a randomised de-escalation trial with tumour-informed ctDNA, and the idea remains speculative.","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT01844986: SOLO-1","url":"https://clinicaltrials.gov/study/NCT01844986"},{"label":"ClinicalTrials.gov NCT02655016: PRIMA / ENGOT-OV26","url":"https://clinicaltrials.gov/study/NCT02655016"}],"tags":[],"related":[],"cancers":["ovarian"],"sections":[],"technologies":["mrd-testing","parp-inhibitor"],"targets":[],"drugs":["olaparib","niraparib"],"companies":[],"institutions":[],"pathways":[],"terms":["mrd"],"trials":["solo-1","prima"],"people":[],"bottlenecks":[],"keyPapers":["paper-solo-1-nejm-2018","paper-niraparib-ovarian-n-engl-j-med-2016","paper-prima-niraparib-nejm-2019"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"ctDNA-negative patients at 12 months can stop PARP maintenance without loss of PFS; ctDNA-positive patients benefit from switching to an ATR or POLQ inhibitor before radiographic progression.","rationale":"MRD-guided de-escalation is proven in colon cancer (DYNAMIC) and bladder (IMvigor011); BRCA reversion is detectable in plasma.","test":"Randomised de-escalation trial with tumour-informed ctDNA at 12 months; primary endpoint 3-year PFS non-inferiority.","maturity":"speculative"},{"id":"idea-ctdna-guided-dlbcl-frontline","kind":"idea","name":"ctDNA-guided escalation and de-escalation in frontline DLBCL","aka":[],"tldr":"Use an ultra-sensitive blood test after two cycles to decide who needs more than R-CHOP and who can stop early.","summary":"The idea is to use an ultra-sensitive ctDNA assay such as PhasED-seq after two cycles of R-CHOP in frontline diffuse large B-cell lymphoma to decide who needs escalation and who can stop early. Interim PET has poor positive predictive value, whereas ctDNA clearance after cycle 2 or at end of treatment predicts cure better, and ctDNA kinetics track outcome across cohorts. The hypothesis is that patients with undetectable ctDNA after two cycles do as well with four cycles as six, while those with detectable ctDNA benefit from switching to a bispecific-containing regimen such as epcoritamab-R-CHOP. The test is a randomised response-adapted trial with ctDNA-defined arms, non-inferior for de-escalation and superior for escalation on event-free survival.","asOf":"2026-09-07","links":[{"label":"Kurtz et al., Circulating tumour DNA measurements as early outcome predictors in diffuse large B-cell lymphoma (Journal of Clinical Oncology 2018)","url":"https://doi.org/10.1200/JCO.2018.78.5246"}],"tags":[],"related":[],"cancers":["dlbcl"],"sections":[],"technologies":["ctdna-lymphoma-monitoring"],"targets":[],"drugs":["epcoritamab","polatuzumab-vedotin"],"companies":[],"institutions":[],"pathways":[],"terms":["mrd"],"trials":["epcore-dlbcl-1","epcore-dlbcl-2","epcore-nhl-1","nct06508658","nct07226752"],"people":[],"bottlenecks":[],"keyPapers":["paper-kurtz-j-clin-oncol","paper-epcoritamab-dlbcl-drugs-2023","paper-epcoritamab-dlbcl-blood-2025"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Patients with undetectable ctDNA after two cycles of R-CHOP have equivalent EFS with 4 versus 6 cycles; patients with detectable ctDNA benefit from switching to a bispecific-containing regimen.","rationale":"Interim PET has poor positive predictive value; ctDNA kinetics correlate with outcome across cohorts.","test":"Randomised response-adapted trial with ctDNA-defined arms and EFS non-inferiority (de-escalation) and superiority (escalation) endpoints.","maturity":"early-clinical"},{"id":"idea-btc-ctdna-fgfr-resistance","kind":"idea","name":"ctDNA-guided switching among FGFR inhibitors","aka":[],"tldr":"Track FGFR2 resistance mutations in blood and switch to the next-generation inhibitor that still covers them, before the scan shows progression.","summary":"In biliary tract cancer driven by FGFR2 fusions, resistance to pemigatinib and futibatinib arises through polyclonal FGFR2 kinase-domain mutations that appear in cell-free DNA weeks before scans show progression. The idea is to monitor plasma ctDNA serially and switch pre-emptively to a next-generation inhibitor such as tinengotinib or lirafugratinib that still covers the emerging mutation. The rationale is that these resistance mutations are drug-specific and predictable, and molecular progression precedes clinical progression. The proposed test is a randomised phase 2 of ctDNA-triggered versus imaging-triggered switching with time to chemotherapy as the endpoint, at an early clinical stage, bearing on the liquid biopsy and kinase inhibitor technologies and the FGFR2 target.","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT02924376: FIGHT-202","url":"https://clinicaltrials.gov/study/NCT02924376"},{"label":"ClinicalTrials.gov NCT02052778: FOENIX-CCA2","url":"https://clinicaltrials.gov/study/NCT02052778"}],"tags":[],"related":[],"cancers":["cholangiocarcinoma"],"sections":[],"technologies":["liquid-biopsy","kinase-inhibitors"],"targets":["fgfr2"],"drugs":["pemigatinib","futibatinib","tinengotinib"],"companies":[],"institutions":[],"pathways":[],"terms":["fgfr2-fusion","ctdna"],"trials":["fight-202","fight-302","first-308","nct05948475","nct07710885"],"people":[],"bottlenecks":[],"keyPapers":["paper-fgfr2-cholangiocarcinoma-annu-rev-med-2023","paper-fgfr2-cholangiocarcinoma-cancers-basel-2026","paper-fgfr2-cholangiocarcinoma-int-j-mol-sci-2025"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Serial ctDNA monitoring with pre-emptive switching to a resistance-mutation-covering FGFR inhibitor extends time on FGFR-directed therapy compared with switching at radiographic progression.","rationale":"Resistance mutations are drug-specific and predictable; molecular progression precedes clinical progression.","test":"Randomised phase 2: ctDNA-triggered switch vs standard imaging-triggered switch; endpoint time to chemotherapy.","maturity":"early-clinical"},{"id":"idea-ctdna-escalation-tnbc","kind":"idea","name":"ctDNA-triggered escalation in early TNBC","aka":[],"tldr":"Instead of treating everyone after surgery, test blood every few months and treat only when tumour DNA reappears.","summary":"Instead of treating every early TNBC patient after surgery, this idea tests blood every few months and escalates only when tumour DNA reappears. MRD-positive patients would be randomised to immediate ADC plus immunotherapy versus surveillance, while MRD-negative patients could omit adjuvant pembrolizumab. IMvigor011 proved the concept in bladder cancer, TNBC relapses early and sheds ctDNA, and the ZEST trial failed on feasibility rather than concept. The test is a platform trial in post-KEYNOTE-522 patients with serial Signatera-type testing, arms of Dato-DXd, sacituzumab govitecan or sac-TMT and a DFS endpoint. At early-clinical maturity it addresses the bottleneck Dormant cells and minimal residual disease.","asOf":"2026-09-04","links":[{"label":"ClinicalTrials.gov NCT04660344: IMvigor011","url":"https://clinicaltrials.gov/study/NCT04660344"},{"label":"ClinicalTrials.gov NCT05812807: OptimICE-pCR (A012103)","url":"https://clinicaltrials.gov/study/NCT05812807"}],"tags":[],"related":["ctdna-mrd-to-adjuvant"],"cancers":["tnbc"],"sections":[],"technologies":["mrd-testing","adc"],"targets":[],"drugs":["signatera"],"companies":[],"institutions":[],"pathways":[],"terms":["mrd"],"trials":["imvigor011","optimice-pcr"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"MRD-positive TNBC patients randomised to immediate ADC + IO have superior DFS versus surveillance, and MRD-negative patients can safely omit adjuvant pembrolizumab.","rationale":"Lead time of 6-12 months over imaging; treating microscopic disease with ADCs may be curative where treating macroscopic relapse is not.","test":"Platform trial enrolling post-KEYNOTE-522 patients with serial Signatera-type testing; randomise MRD+ to intervention arms (Dato-DXd, sacituzumab, sac-TMT) vs observation; primary endpoint DFS; embed a de-escalation arm for MRD-negative pCR patients.","maturity":"early-clinical"},{"id":"idea-cthpv-adapted-deescalation","kind":"idea","name":"ctHPV-DNA-adapted de-escalation of chemoradiation","aka":[],"tldr":"Instead of guessing from HPV status who can get less radiation, measure the virus DNA in blood during treatment and reduce dose only when it clears fast.","summary":"The idea is to reduce the radiation dose in HPV-positive head and neck cancer only for patients whose circulating tumour HPV DNA clears quickly during treatment, rather than for everyone who is HPV-positive. NRG-HN005 showed that static selection on HPV status fails, whereas ctHPV-DNA kinetics track tumour kill in real time and outperform baseline staging for predicting recurrence. The hypothesis is that patients whose ctHPV-DNA clears by week 2 to 3 of chemoradiation can receive 60 Gy without loss of progression-free survival, while non-clearers receive the full 70 Gy. The test is a phase 2/3 trial of ctHPV-DNA-guided dose versus uniform 70 Gy, with progression-free survival and quality of life as endpoints; the idea sits on the radiotherapy roadmap.","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT03952585: NRG-HN002 & NRG-HN005 (HPV+ de-escalation)","url":"https://clinicaltrials.gov/study/NCT03952585"}],"tags":[],"related":[],"cancers":["head-and-neck"],"sections":[],"technologies":["cthpv-dna","imrt-igrt"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["hpv-p16"],"trials":["nrg-hn002-hn005"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Patients whose ctHPV-DNA clears by week 2-3 of chemoradiation can receive 60 Gy without loss of PFS, while non-clearers receive 70 Gy.","rationale":"ctHPV-DNA kinetics track tumour kill in real time and outperform baseline staging for predicting recurrence.","test":"Phase 2/3 with ctHPV-DNA-guided dose assignment versus uniform 70 Gy; PFS non-inferiority in clearers and quality-of-life superiority.","maturity":"early-clinical"},{"id":"idea-prev-hcv-test-treat-surveillance-linkage","kind":"idea","name":"Cure hepatitis C in prisons and drug services, and enrol the cured in liver cancer surveillance","aka":[],"tldr":"Hepatitis C is now curable in weeks. Testing and treating where it is concentrated, and keeping those with scarring in surveillance afterwards, would cut liver cancer.","summary":"Hepatitis C is now curable in weeks, so this idea introduces opt-out testing and immediate direct-acting antiviral treatment in prisons and needle services, then automatically enrols cured patients with F3 or F4 fibrosis into liver cancer surveillance, blood-based where possible. Cure does not remove hepatocellular carcinoma risk in advanced fibrosis, and while elimination programmes in Egypt, Georgia and Australia show feasibility, the surveillance step is usually missing. The aim is fewer and earlier-stage liver cancers among people who inject drugs. The test is a regional programme with registry evaluation. Being tested at scale, it addresses the bottlenecks Prevention we already have is not deployed and Fragmented care and guideline gaps.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Prevention we already have is not deployed): Islami et al., Proportion of cancer attributable to modifiable risk factors (CA 2018)","url":"https://doi.org/10.3322/caac.21440"}],"tags":[],"related":[],"cancers":["hcc"],"sections":["prevention"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption","b-care-fragmentation"],"keyPapers":["paper-islami-ca-cancer-j-clin"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Opt-out test-and-treat with surveillance linkage reduces HCC incidence and late-stage HCC among people who inject drugs by at least 40% within a decade.","rationale":"Elimination programmes in Egypt, Georgia and Australia show feasibility; the surveillance step is usually missing.","test":"Run a regional programme with registry evaluation.","maturity":"being-tested-at-scale","actor":"policy","cost":"medium","horizonYears":6},{"id":"idea-moon-cure-prizes","kind":"idea","name":"Cure-focused prizes: pay for verified long-term cures, not for drugs","aka":[],"tldr":"Governments and philanthropists commit large payments for whoever achieves a verified jump in ten-year cure rates for a specific cancer, however they do it.","summary":"Drug incentives reward incremental progression-free survival in late-stage disease; nothing rewards curing. Prize and advance market commitment mechanisms have worked for vaccines and longitude. The proposal is a set of cure prizes, each defined as a verified increase in a specific cancer's five- or ten-year relapse-free survival in a defined population (for example, pancreatic adenocarcinoma stage II, glioblastoma, metastatic triple-negative breast cancer), funded by pooled public and philanthropic commitments, awarded on registry-verified population outcomes with pro-rata payments for partial progress and open licensing conditions.","asOf":"2026-09-08","links":[{"label":"Cancer Grand Challenges","url":"https://cancergrandchallenges.org/"},{"label":"XPRIZE","url":"https://www.xprize.org/"}],"tags":[],"related":[],"cancers":["pancreatic","glioblastoma","tnbc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-funding-allocation","b-incentive-misalignment"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Announced cure prizes redirect measurable private and academic investment toward curative-intent strategies (combinations, interception, cell therapy) in the named cancers within three years and produce at least one verified prize-level improvement within fifteen.","rationale":"Investment follows expected payment; today's payment structure is indifferent to cure. Prizes pay only on success and let the market choose the route.","test":"Launch three prizes with an independent verification body using cancer registries; track investment flows and trial starts in the named cancers against matched controls.","maturity":"speculative","actor":"philanthropy","cost":"large","horizonYears":10},{"id":"idea-bio1-stress-response-blockade","kind":"idea","name":"Cut off the emergency programme cancer cells use to survive treatment","aka":[],"tldr":"When attacked, cells switch on a survival programme that buys them time to adapt. Blocking that programme could turn a partial response into a complete one.","summary":"The integrated stress response, heat shock factor 1 activity and autophagy are rapidly induced after targeted therapy and support survival during the adaptation window. Inhibitors of eIF2B-mediated stress signalling, HSF1 and autophagy exist at various stages of development. The proposal is combination timed to the adaptation window (the first days after therapy initiation) rather than continuous co-dosing.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Acquired resistance to every therapy): Soria et al., Osimertinib in untreated EGFR-mutated NSCLC (FLAURA, NEJM 2018)","url":"https://doi.org/10.1056/NEJMoa1713137"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["resistance","mrd"],"trials":[],"people":[],"bottlenecks":["b-resistance"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Blocking the acute stress response during the first days of targeted therapy increases the depth of response, measured by residual tumour cell number or ctDNA nadir, compared with the targeted agent alone.","rationale":"Adaptation precedes mutation; models consistently show a survival advantage from stress-response activation, and the window is short so exposure and toxicity can be limited.","test":"Preclinical combination studies with ctDNA-equivalent depth-of-response readouts, followed by a window-of-opportunity clinical study measuring residual disease at two weeks.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":6},{"id":"idea-nerve-tumour-blockade","kind":"idea","name":"Cut the nerve supply to tumours with old drugs","aka":[],"tldr":"Nerves feed pancreatic, prostate, and other tumours. Beta-blockers and botulinum toxin are cheap, safe, and already in trials to see if severing that link slows cancer.","summary":"This idea proposes cutting the nerve supply to tumours with old drugs: nerves feed pancreatic, prostate and other tumours, and beta-blockers and botulinum toxin are cheap, safe and in trials. Propranolol reduced proliferation markers in window trials, denervation slowed gastric cancer in mice, perampanel targets glioma synapses, and perineural invasion is strongly prognostic. The hypothesis, rooted in the Cancer neuroscience pathway, is that beta-blockade or denervation added to standard therapy improves outcomes in tumours with high perineural invasion or an adrenergic signature. The tests are a randomised phase 2 of propranolol in resectable Pancreatic ductal adenocarcinoma and a perampanel trial in Glioma & glioblastoma; Prostate cancer is also in scope.","asOf":"2026-09-08","links":[{"label":"Zahalka et al., Adrenergic nerves activate an angio-metabolic switch in prostate cancer (Science 2017)","url":"https://doi.org/10.1126/science.aah5072"}],"tags":["mechanism","open-question"],"related":[],"cancers":["pancreatic","glioblastoma","prostate","head-and-neck"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["stanford","md-anderson","mskcc"],"pathways":["cancer-neuroscience"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-zahalka-science"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Adding β-blockade (or local denervation) to standard therapy improves outcomes in tumours with high perineural invasion or adrenergic signature.","rationale":"Strong preclinical mechanism (Monje, Amit, Zahalka), epidemiologic signals for β-blocker users, low cost and toxicity.","test":"Randomised phase 2 of propranolol vs placebo added to standard therapy in resectable pancreatic cancer with perineural invasion, endpoint DFS; glioma trial of perampanel plus standard therapy with growth-rate endpoint.","maturity":"early-clinical"},{"id":"idea-bio2-lactate-acid-axis","kind":"idea","name":"De-acidify the tumour so T cells can work in it","aka":[],"tldr":"Tumours are acidic, and immune cells stop working in acid. Neutralising that acid, or blocking the pumps that create it, might let immunotherapy work.","summary":"Tumour lactate export via MCT1 and MCT4 acidifies the microenvironment and directly impairs T-cell and natural killer cell function, while feeding regulatory T cells. Oral buffer therapy reversed acid-mediated immune exclusion in mouse models, and MCT1 inhibitors have been in early clinical trials. Nobody has tested pH modulation with a pH-imaging readout in patients receiving checkpoint blockade.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Cold tumours and the immunosuppressive microenvironment): Haslam & Prasad, Estimation of the percentage of US patients eligible for and responding to checkpoint inhibitors (JAMA Netw Open 2019)","url":"https://doi.org/10.1001/jamanetworkopen.2019.2535"}],"tags":[],"related":[],"cancers":["pancreatic","melanoma"],"sections":[],"technologies":["checkpoint-inhibitor","mri","fdg-pet"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["cold-vs-hot","suv"],"trials":[],"people":[],"bottlenecks":["b-tme-immunosuppression","b-immunotherapy-response"],"keyPapers":["paper-haslam-jama-netw-open"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Raising intratumoural pH, measured by a validated imaging or biopsy method, increases intratumoural T-cell function markers and improves checkpoint blockade response in acidic, glycolysis-high tumours.","rationale":"Acid inhibition of T cells is well replicated in vitro and in mice, and pH is a tractable, measurable and potentially drug-independent variable. Selecting patients by tumour acidity is the missing step, and MRI and PET methods for tumour pH exist in research settings.","test":"A window-of-opportunity trial combining an approved checkpoint inhibitor with buffer therapy or an MCT inhibitor in glycolysis-high tumours, with pH imaging and paired biopsies as primary endpoints.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":8},{"id":"idea-lung-screening-eligibility-by-risk-not-pack-years","kind":"idea","name":"Decide who is screened for lung cancer by individual risk, not by pack-years","aka":[],"tldr":"The rules that decide who gets a lung scan count cigarettes. A risk model that also uses age, sex, family history, deprivation and lung disease would find more cancers in the same number of scans, and would stop excluding people who smoke less but are more likely to get the disease.","summary":"Eligibility for low-dose computed tomography screening is defined in the United States by age 50 to 80 with a 20 pack-year history and quitting within 15 years, and elsewhere by variations on the same two numbers. Aldrich showed what that costs: in a southern United States cohort 31 percent of white smokers were eligible against 17 percent of Black smokers, who develop lung cancer at lower cumulative exposure. Risk prediction models have been shown to select a higher-yield population than pack-year thresholds at the same screening volume, and the 2021 task force update considered them and did not adopt them.\n\nThe idea is to make risk-model eligibility the default, prospectively evaluated against threshold eligibility on cancers detected per thousand screened, stage distribution and the equity of who is invited, rather than on eligibility counts. UK and NHS specifics (Targeted Lung Health Check coverage and uptake, NICE positions and Cancer Drugs Fund status, molecular testing turnaround, thoracic surgery and radiotherapy capacity, audit indicators and trial access) are on the UK and NHS page for lung cancer and are not restated here.","asOf":"2026-09-25","links":[],"tags":["lung-evidence"],"related":["idea-prev-lung-screening-risk-model-eligibility","idea-prev-screening-default-appointments","early-detection-roadmap","lung-cancer-evidence-roadmap"],"cancers":["lung-cancer","nsclc"],"sections":["early-detection","prevention"],"technologies":["low-dose-ct-screening"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-early-detection","b-trial-diversity","b-global-access","b-prevention-adoption"],"keyPapers":["paper-aldrich-uspstf-screening-african-american-smokers-jama-oncol-2019","paper-uspstf-lung-cancer-screening-jama-2021","paper-nlst-nejm-2011","paper-nelson-nejm-2020"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Replacing pack-year eligibility with an individual risk model detects more stage I and II lung cancers per thousand scans and narrows the gap in eligibility between the most and least deprived populations, without increasing the false-positive rate per cancer found.","rationale":"Pack-years are a single crude proxy for a risk that depends on age, duration and intensity of smoking, years since quitting, sex, chronic obstructive pulmonary disease, family history, occupational and particulate exposure and deprivation. A threshold on one variable cannot be calibrated across populations that differ on the others, and Aldrich's 31 against 17 percent is the measured consequence. Risk models also give a natural route to including never-smokers with other risk factors, who are currently excluded by construction.","test":"A pragmatic randomised comparison inside an existing screening programme: invitation by threshold eligibility against invitation by a validated risk model at matched screening capacity, with cancers detected by stage, interval cancers, false-positive rate per cancer found and eligibility by deprivation quintile and ethnicity as co-primary outcomes. Three years to first readout on detection, ten to mortality.","maturity":"early-clinical","actor":"policy","cost":"medium","horizonYears":5},{"id":"idea-acc-embedded-decision-aids","kind":"idea","name":"Decision aids built into the record for every preference-sensitive cancer choice","aka":[],"tldr":"Choices like mastectomy versus lumpectomy, or whether to have chemotherapy after surgery, depend on what matters to the patient. Good decision aids exist but are rarely used; building them into the clinic workflow would change that.","summary":"Decision aids improve knowledge, reduce decisional conflict, and often shift choices toward less intensive treatment in randomised trials, yet routine use is rare. Embedding validated aids into the electronic record so that they are triggered at the relevant decision point, pre-populated with the patient's own risk estimates, and documented as part of consent would make shared decision-making the default rather than an add-on.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Fragmented care and guideline gaps): Hanna et al., Mortality due to cancer treatment delay: systematic review and meta-analysis (BMJ 2020)","url":"https://doi.org/10.1136/bmj.m4087"}],"tags":[],"related":[],"cancers":["breast-hr-positive","prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-care-fragmentation","b-patient-voice"],"keyPapers":["paper-hanna-bmj"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Embedding decision aids will increase documented shared decision-making for defined choices from under 30% to above 80% of eligible consultations and reduce decisional regret at six months.","rationale":"Cochrane reviews show consistent benefits; the implementation literature shows that aids used only when clinicians remember them are rarely used at all.","test":"A stepped-wedge rollout across eight breast and prostate services measuring use, decisional conflict, treatment choices, and regret.","maturity":"early-clinical","actor":"clinic","cost":"small","horizonYears":2},{"id":"idea-data-provenance-first-decision-support","kind":"idea","name":"Decision support that cites the exact trial and guideline line it relies on","aka":[],"tldr":"When a computer suggests a treatment, it should show the doctor the specific trial result and guideline sentence behind the suggestion, so it can be checked and trusted.","summary":"Most oncology decision support presents recommendations as opaque rules. Provenance-first CDS attaches, to every suggestion, the guideline version and recommendation identifier, the trial identifiers and structured results it derives from, and the date of last evidence check, drawn from a computable guideline feed and evidence graph. This makes recommendations auditable, updatable and correctable, and lets clinicians see when evidence is thin.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Knowledge reaches practice too slowly): Morris, Wooding & Grant, The answer is 17 years, what is the question (JRSM 2011)","url":"https://doi.org/10.1258/jrsm.2011.110180"}],"tags":[],"related":["idea-data-computable-living-guidelines","idea-data-open-evidence-knowledge-graph"],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-knowledge-diffusion","b-ai-validation"],"keyPapers":["paper-morris-j-r-soc-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Clinicians will accept provenance-first CDS suggestions at a higher rate and override them more appropriately than opaque CDS, and errors introduced by stale rules will be detected faster.","rationale":"Trust in decision support depends on verifiability; in other domains (legal research, code review) tools that cite sources outperform those that do not in adoption and accuracy.","test":"Randomise oncologists in a simulation study to opaque versus provenance-first CDS for 40 cases with planted stale recommendations; measure appropriate acceptance, override and error detection.","maturity":"early-clinical","actor":"engineering","cost":"small","horizonYears":2},{"id":"idea-tr1-ecog-2-dedicated-cohorts","kind":"idea","name":"Dedicated cohorts for patients with performance status 2 in first-line trials","aka":[],"tldr":"Trials usually take only patients who are up and about most of the day. Those who spend more time resting, a common group in real clinics, are excluded, so nobody knows how to treat them. A dedicated group in each trial would answer that.","summary":"First-line trials of new regimens include a pre-specified ECOG performance status 2 cohort, randomised where feasible, with safety-led dose modification, primary endpoints appropriate to the population (OS, time on treatment, QoL) and reporting in the label. Some lung cancer trials have run dedicated PS2 studies; the proposal generalises this.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Trials do not represent the people who get cancer): Loree et al., Disparity of race reporting and representation in trials leading to cancer drug approvals (JAMA Oncology 2019)","url":"https://doi.org/10.1001/jamaoncol.2019.1870"}],"tags":[],"related":[],"cancers":["nsclc","pancreatic","gastric","esophageal"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-diversity","b-aging-comorbidity"],"keyPapers":["paper-loree-jama-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"PS2 cohorts will show that benefit is preserved for some regimens and absent or harmful for others, information that changes real-world prescribing for a population that currently receives extrapolated care.","rationale":"PS2 patients are a sizeable share of real-world first-line recipients, especially in lung, pancreatic and upper gastrointestinal cancers, and receive full-dose regimens tested only in fitter patients.","test":"Require PS2 cohorts in first-line registrational trials for three cancers with high PS2 prevalence and track the resulting label statements and real-world outcomes.","maturity":"early-clinical","actor":"industry","cost":"medium","horizonYears":3},{"id":"idea-acc-default-fertility-preservation-referral","kind":"idea","name":"Default fertility preservation referral for every patient under 40 before treatment","aka":[],"tldr":"Fewer than half of patients starting treatment that can damage fertility have a documented fertility discussion or referral, with worse rates for women, minorities and patients outside academic centres. An order-set trigger that refers every patient under 40 to reproductive medicine unless they actively decline would make the conversation routine and timely.","summary":"Guidelines require discussion of fertility preservation before gonadotoxic therapy, yet documented discussion and referral rates remain well below half in published series, with worse rates for women, minorities, and patients at non-academic centres. An order-set trigger that creates a fertility referral for every patient under 40 unless actively declined, with a fast-track reproductive medicine pathway and funding for preservation, would close this gap.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Survivorship and late effects are neglected): NCI Office of Cancer Survivorship statistics","url":"https://cancercontrol.cancer.gov/ocs/statistics"}],"tags":[],"related":[],"cancers":["hodgkin-lymphoma","tnbc","all-leukemia"],"sections":["supportive-care","rejuvenation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-care-fragmentation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Default referral will raise documented fertility counselling to above 90% of eligible patients and double the proportion undergoing preservation, without delaying treatment start by more than a week.","rationale":"Defaults outperform reminders; the time-critical nature of preservation means that a missed conversation is irreversible.","test":"Run a stepped-wedge implementation across ten centres with counselling documentation, preservation uptake, treatment delay, and regret at two years.","maturity":"being-tested-at-scale","actor":"clinic","cost":"small","horizonYears":2},{"id":"idea-tr1-justify-every-exclusion","kind":"idea","name":"Default-inclusive eligibility: sponsors must justify every exclusion criterion","aka":[],"tldr":"Trials should let people in unless there is a scientific or safety reason to keep them out. Every exclusion rule would need a written reason, reviewed like the rest of the protocol.","summary":"Regulators and ethics committees would require a one-line scientific or safety justification for each exclusion criterion, with a default set of permitted criteria (the ASCO-Friends of Cancer Research broadened criteria on brain metastases, organ function, prior malignancies, HIV and hepatitis) needing no justification and anything stricter needing one. The FDA's 2020 eligibility guidances describe what is reasonable; this idea makes the reasonable set the default and puts the burden of proof on restriction.","asOf":"2026-09-08","links":[{"label":"FDA: Enhancing the Diversity of Clinical Trial Populations (guidance)","url":"https://www.fda.gov/regulatory-information/search-fda-guidance-documents/enhancing-diversity-clinical-trial-populations-eligibility-criteria-enrollment-practices-and-trial"},{"label":"Friends of Cancer Research","url":"https://friendsofcancerresearch.org/"}],"tags":[],"related":["clinicaltrials-gov"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["asco","nci"],"pathways":[],"terms":["standard-of-care"],"trials":[],"people":[],"bottlenecks":["b-trial-enrolment","b-trial-diversity"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Protocols written under a justify-every-exclusion rule will have at least a third fewer exclusion criteria and a measurably higher fraction of real-world patients eligible (as simulated against a real-world oncology dataset), without an increase in grade 5 adverse events attributable to the broadened population.","rationale":"Analyses of protocol eligibility against real-world data show that many criteria are copied from earlier protocols and that relaxing them changes the eligible pool substantially with little effect on the estimated hazard ratio. Ethics review already asks for justification of risk; asking for justification of exclusion is symmetric and cheap.","test":"A cooperative group or single regulator pilots the rule for 12 months on all new phase 2/3 oncology protocols, comparing criterion counts, simulated eligible fraction and later serious-adverse-event rates against the prior year's protocols.","maturity":"early-clinical","actor":"regulator","cost":"small","horizonYears":2},{"id":"idea-tr1-tolerability-estimands","kind":"idea","name":"Define tolerability endpoints as rigorously as efficacy endpoints","aka":[],"tldr":"Trials report side effects as a table of percentages that hides how long they lasted, how bad they felt and whether people stopped treatment. Tolerability should be measured with defined endpoints and a decision rule, like efficacy.","summary":"Protocols pre-specify tolerability estimands under ICH E9(R1): time to first dose modification, cumulative patient-reported symptom burden (PRO-CTCAE), treatment discontinuation for toxicity, and a toxicity-over-time summary, with hypotheses and analysis plans. Regulators include a tolerability summary in the label, and dose-optimisation decisions reference it.","asOf":"2026-09-08","links":[{"label":"PRO-CTCAE (NCI)","url":"https://healthcaredelivery.cancer.gov/pro-ctcae/"},{"label":"ICH efficacy guidelines (E9(R1) estimands)","url":"https://www.ich.org/page/efficacy-guidelines"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["irae"],"trials":[],"people":[],"bottlenecks":["b-trial-design","b-toxicity-qol","b-dose-optimisation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Pre-specified tolerability endpoints will change the interpretation of at least a fifth of positive phase 3 trials (identifying regimens where efficacy gains are offset by tolerability losses) and will improve concordance between label and real-world persistence.","rationale":"Maximum-grade tables ignore duration and patient perspective; PRO-CTCAE and longitudinal toxicity analyses exist but are secondary and rarely pre-specified with a decision rule.","test":"Apply the tolerability estimand framework to trials with existing PRO-CTCAE data and compare conclusions with the original safety tables; then mandate it for a cohort of new registrational trials.","maturity":"early-clinical","actor":"regulator","cost":"small","horizonYears":2},{"id":"idea-bio1-mutant-p53-degrader","kind":"idea","name":"Degrade the damaged p53 protein rather than trying to repair it","aka":[],"tldr":"Some faulty p53 proteins do not just stop protecting the cell; they actively help the cancer. Removing them entirely may be easier than fixing them.","summary":"Gain-of-function mutant p53 accumulates to high levels because it escapes MDM2-mediated turnover, and it drives invasion and chemoresistance in mouse models. A selective degrader exploiting the mutant's dependence on HSP90 or its distinct conformation could deplete it. Precedent: HSP90 inhibitors destabilise mutant p53 and prolong survival in mutant-p53 mouse models, but are too toxic; a targeted degrader would separate the effect from global chaperone inhibition.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The undruggable drivers): Dang et al., Drugging the 'undruggable' cancer targets (Nature Reviews Cancer 2017)","url":"https://doi.org/10.1038/nrc.2017.36"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["protac-degrader"],"targets":["tp53"],"drugs":[],"companies":[],"institutions":[],"pathways":["p53-cell-cycle"],"terms":[],"trials":[],"people":[],"bottlenecks":["b-undruggable-targets"],"keyPapers":["paper-dang-nat-rev-cancer"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Selective depletion of gain-of-function mutant p53 reduces metastasis and restores chemotherapy sensitivity in mutant-p53 models without affecting wild-type p53 in normal tissue.","rationale":"Mutant p53 accumulation is a distinguishing feature of tumour cells, which gives a natural therapeutic index; degradation is the modality of choice for proteins whose function is structural rather than enzymatic.","test":"Degrader discovery against R175H and R273H with conformation-selective binders; validate in genetically engineered mutant-p53 mouse models measuring metastasis and chemosensitivity.","maturity":"speculative","actor":"research","cost":"medium","horizonYears":8},{"id":"idea-bio1-fusion-tf-degraders","kind":"idea","name":"Degraders for the fusion proteins that drive childhood sarcomas","aka":[],"tldr":"Some sarcomas in children are caused by two genes fused into one abnormal protein. That protein is the whole disease, but no drug binds it. Destroying it instead of blocking it could work.","summary":"EWS-FLI1 in Ewing sarcoma and PAX3-FOXO1 in alveolar rhabdomyosarcoma are single, tumour-specific, genetically validated drivers with no enzymatic activity. Degradation via recruited E3 ligases, or indirect destabilisation through their obligate cofactors (for example BRD9 in the ncBAF complex for synovial sarcoma, already showing clinical activity with BRD9 degraders), offers a route. Their absence from normal tissue means an unusually wide therapeutic index.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The undruggable drivers): Dang et al., Drugging the 'undruggable' cancer targets (Nature Reviews Cancer 2017)","url":"https://doi.org/10.1038/nrc.2017.36"}],"tags":[],"related":[],"cancers":["sarcoma"],"sections":[],"technologies":["protac-degrader","crispr-screens","pdx-models"],"targets":[],"drugs":[],"companies":["c4-therapeutics"],"institutions":[],"pathways":[],"terms":["gene-fusion"],"trials":[],"people":[],"bottlenecks":["b-undruggable-targets","b-rare-cancers"],"keyPapers":["paper-dang-nat-rev-cancer"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A degrader that lowers fusion protein levels by 70 percent causes tumour regression in patient-derived fusion-positive sarcoma models, with no effect on fusion-negative controls.","rationale":"The BRD9 degrader experience in synovial sarcoma shows that attacking a complex member of a fusion-driven transcriptional programme is clinically tractable; fusion drivers are the cleanest targets in oncology if a modality can reach them.","test":"Parallel degrader campaigns against the fusion proteins and their obligate cofactors, prioritised by CRISPR dependency data, then testing in paediatric PDX panels with the Paediatric Preclinical Testing Consortium.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":7},{"id":"idea-bio2-intraventricular-car-t","kind":"idea","name":"Deliver CAR-T cells straight into the fluid around the brain","aka":[],"tldr":"Cancer spreading along the linings of the brain has no treatment that reliably controls it. Injecting engineered immune cells directly into the brain fluid, through a small reservoir, reaches it.","summary":"Intraventricular delivery of HER2-directed CAR-T cells via an Ommaya reservoir has produced responses in leptomeningeal metastasis in early trials at City of Hope, and intrathecal chemotherapy is long-established. Local delivery avoids the barrier entirely, gives high local cell dose and appears to reduce systemic cytokine toxicity.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The brain: barrier and sanctuary): Stupp et al., Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma (NEJM 2005)","url":"https://doi.org/10.1056/NEJMoa043330"}],"tags":[],"related":[],"cancers":["breast-her2-positive","glioblastoma"],"sections":[],"technologies":["car-t","glioma-car-t"],"targets":["her2","b7h3"],"drugs":[],"companies":[],"institutions":["city-of-hope"],"pathways":[],"terms":["her2-brain-metastases","crs"],"trials":[],"people":[],"bottlenecks":["b-brain-delivery","b-metastasis-biology"],"keyPapers":["paper-slamon-her2-breast-ovarian-science-1989","paper-yarden-sliwkowski-erbb-network-nrmcb-2001"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Repeat intraventricular CAR-T dosing produces cerebrospinal fluid tumour cell clearance in at least a third of patients with leptomeningeal metastasis, with median survival better than the current two to four months.","rationale":"The cerebrospinal fluid is a closed, low-volume compartment where a small number of cells produces high effective concentration, and cell products can be re-dosed through an implanted reservoir without repeated surgery.","test":"A multi-centre phase 2 in HER2-positive breast cancer leptomeningeal disease with cerebrospinal fluid cytology and ctDNA clearance as primary endpoints, and quality of life measured throughout.","maturity":"early-clinical","actor":"clinic","cost":"medium","horizonYears":5},{"id":"idea-bio2-intranasal-delivery","kind":"idea","name":"Deliver drugs and cells to the brain through the nose","aka":[],"tldr":"The nerves at the top of the nose lead directly into the brain, bypassing the barrier. Nasal delivery of drugs, and even immune cells, has worked in animals.","summary":"Intranasal administration reaches the brain along olfactory and trigeminal pathways, and preclinical work has delivered chemotherapy, oncolytic virus and natural killer cells to glioma models by this route. Human doses of intranasal insulin and perampanel demonstrate the route works pharmacologically, but delivered fractions are small and highly formulation-dependent.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The brain: barrier and sanctuary): Stupp et al., Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma (NEJM 2005)","url":"https://doi.org/10.1056/NEJMoa043330"}],"tags":[],"related":[],"cancers":["glioblastoma"],"sections":[],"technologies":["oncolytic-virus","car-nk-macrophage","cytotoxic-chemotherapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["blood-brain-barrier"],"trials":[],"people":[],"bottlenecks":["b-brain-delivery","b-global-access"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"An optimised intranasal formulation delivers a therapeutically relevant concentration to human brain tissue, measurable in resected tumour or by microdialysis, at a fraction of the systemic exposure required intravenously.","rationale":"The route completely bypasses the barrier and requires no device or surgery, so it would be uniquely suitable for repeated or chronic dosing and for use in resource-limited settings. The key unknown is human delivered fraction, which is directly measurable.","test":"A pharmacokinetic study in patients scheduled for tumour resection: intranasal dosing before surgery with drug quantification in resected tumour and plasma to establish the brain-to-plasma ratio achieved.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":8},{"id":"idea-tr2-raw-image-deposit","kind":"idea","name":"Deposit the raw blots, gels and microscopy images behind every figure","aka":[],"tldr":"Published figures are cropped and processed. Requiring the original, uncropped image files to be deposited lets anyone check that the figure shows what it claims.","summary":"Western blot and microscopy figures are the most common site of error and manipulation in biomedical papers. Some journals now request uncropped blots as supplementary files; deposit in a public repository with checksums and metadata (instrument, exposure, processing steps) would make verification and re-analysis possible and would deter selective cropping and splicing.","asOf":"2026-09-08","links":[{"label":"BioImage Archive","url":"https://www.ebi.ac.uk/bioimage-archive/"}],"tags":[],"related":["idea-tr2-automated-stats-check","idea-tr2-data-link-enforcement"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-reproducibility"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Mandatory raw image deposit reduces image-related corrections and retractions at adopting journals by at least half over five years relative to non-adopting journals.","rationale":"Sequencing data deposit became universal within a decade of being mandated and enabled a generation of re-analysis; imaging data can follow.","test":"Two journals mandate deposit; audit a random sample for compliance and for discrepancies between raw and published images; track corrections.","maturity":"early-clinical","actor":"policy","cost":"small","horizonYears":1},{"id":"idea-data-structured-trial-results-deposit","kind":"idea","name":"Deposit trial results as structured data, not just PDFs","aka":[],"tldr":"Trial results (hazard ratios, confidence intervals, subgroups, toxicities) would be deposited in a computer-readable form so they can be pooled, checked and used by software immediately.","summary":"ClinicalTrials.gov results reporting is structured but coarse; journal articles are unstructured; Kaplan-Meier curves are images. The proposal requires deposition of a structured results package (primary and secondary endpoints with estimates and intervals, digitised survival curves or individual patient time-to-event data, subgroup tables, adverse events by grade in CTCAE codes) in a standard schema at publication, enabling automated meta-analysis and living guidelines.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Knowledge reaches practice too slowly): Morris, Wooding & Grant, The answer is 17 years, what is the question (JRSM 2011)","url":"https://doi.org/10.1258/jrsm.2011.110180"}],"tags":[],"related":["clinicaltrials-gov","idea-data-funded-living-systematic-reviews"],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["hazard-ratio","os","pfs"],"trials":[],"people":[],"bottlenecks":["b-knowledge-diffusion","b-negative-results"],"keyPapers":["paper-morris-j-r-soc-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Structured results deposition will make automated living meta-analysis possible for more than 80 percent of new phase 3 oncology trials and will reduce transcription errors in systematic reviews.","rationale":"Extraction from PDFs is the main cost and error source in evidence synthesis; every downstream use (living reviews, guidelines, knowledge graphs, decision support) is faster if results are born structured.","test":"Define the schema; require it for one year in two journals; measure the share of trials complying and the time to update a living review using the structured data versus PDF extraction.","maturity":"early-clinical","actor":"policy","cost":"small","horizonYears":2},{"id":"idea-bio1-evolutionary-double-bind","kind":"idea","name":"Design drug pairs where resisting one makes you vulnerable to the other","aka":[],"tldr":"Choose two treatments so that whatever the tumour does to escape the first, it becomes easier to kill with the second. The immune system is a good candidate partner.","summary":"An evolutionary double bind pairs therapies with opposing selection pressures. Examples with preclinical support include MAPK inhibition increasing antigen presentation (making escape via MAPK reactivation immune-visible) and antiandrogen resistance via lineage plasticity creating dependence on EZH2. The proposal is to make double-bind logic an explicit design criterion, with a mechanistic screen for pairs in which resistance to A upregulates the target of B.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Tumour heterogeneity and clonal evolution): Gerlinger et al., Intratumor heterogeneity and branched evolution (NEJM 2012)","url":"https://doi.org/10.1056/NEJMoa1113205"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":["ezh2","braf"],"drugs":[],"companies":[],"institutions":[],"pathways":["ras-mapk","ar-signaling"],"terms":[],"trials":[],"people":[],"bottlenecks":["b-tumor-heterogeneity","b-resistance","b-combination-space"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Combinations selected for double-bind structure delay resistance in vivo more than combinations selected for additive cytotoxicity, at matched toxicity.","rationale":"Resistance is a phenotype shift; if the shift can be predicted, the second agent can be aimed at the shifted state. This reframes combination discovery from additive killing to evolutionary trap design.","test":"Screen resistant derivative panels for upregulated targetable dependencies, validate the top three pairs in immunocompetent models, and take one pair into a phase 1b with mandatory paired biopsies.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":5},{"id":"idea-bio2-brain-penetrant-glue-degraders","kind":"idea","name":"Design protein degraders small enough to get into the brain","aka":[],"tldr":"New drugs that destroy cancer proteins are usually too big to enter the brain. Making much smaller versions could bring this approach to brain tumours.","summary":"Bifunctional degraders typically exceed the size and polarity limits for passive brain entry, whereas molecular glues such as the thalidomide analogues are small and drug-like, and brain-penetrant glue degraders have been reported in neuroscience programmes. Applying glue chemistry to brain tumour dependencies, including transcription factors and fusion oncoproteins, would open targets that current chemistry cannot reach in the brain.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The brain: barrier and sanctuary): Stupp et al., Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma (NEJM 2005)","url":"https://doi.org/10.1056/NEJMoa043330"}],"tags":[],"related":[],"cancers":["glioblastoma"],"sections":[],"technologies":["protac-degrader","ai-drug-design"],"targets":[],"drugs":[],"companies":["c4-therapeutics","kymera","monte-rosa","nurix"],"institutions":[],"pathways":[],"terms":["blood-brain-barrier"],"trials":[],"people":[],"bottlenecks":["b-brain-delivery","b-undruggable-targets"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Molecular glue degraders can be optimised to an unbound brain-to-plasma ratio above 0.3 while retaining degradation potency, enabling degradation of a central nervous system tumour dependency in vivo.","rationale":"Glue degraders are small enough to obey central nervous system drug-likeness rules, unlike classical bifunctional degraders, and degradation is catalytic so lower brain concentrations may suffice. Neuroscience programmes have already demonstrated brain-penetrant glue chemistry.","test":"A medicinal chemistry campaign with brain exposure as a primary optimisation parameter against one glioma dependency, reporting the brain-to-plasma ratio and in vivo target degradation in tumour tissue.","maturity":"preclinical-evidence","actor":"industry","cost":"medium","horizonYears":9},{"id":"idea-bio1-arv7-degrader","kind":"idea","name":"Destroy the truncated androgen receptor that hormone drugs cannot touch","aka":[],"tldr":"In advanced prostate cancer the AR-V7 splice variant of the androgen receptor lacks the ligand-binding domain that enzalutamide and abiraterone act on, and its presence predicts resistance. A degrader or N-terminal binder that removes the whole protein, variants included, would still work; AR-V7 is already measurable in circulating tumour cells.","summary":"AR-V7 lacks the ligand-binding domain, so enzalutamide and abiraterone cannot act on it, and its presence predicts resistance. Degraders and N-terminal-domain binders that engage full-length AR and its splice variants could restore control. Full-length AR degraders have reached the clinic; variant-competent agents are the unmet need, and AR-V7 status is already measurable in circulating tumour cells.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The undruggable drivers): Dang et al., Drugging the 'undruggable' cancer targets (Nature Reviews Cancer 2017)","url":"https://doi.org/10.1038/nrc.2017.36"}],"tags":[],"related":["prostate-roadmap","idea-prostate-plasticity-surveillance-before-it-is-neuroendocrine"],"cancers":["prostate"],"sections":[],"technologies":["protac-degrader"],"targets":["androgen-receptor"],"drugs":[],"companies":["arvinas"],"institutions":[],"pathways":["ar-signaling"],"terms":[],"trials":[],"people":[],"bottlenecks":["b-undruggable-targets","b-resistance"],"keyPapers":["paper-dang-nat-rev-cancer","paper-androgen-receptor-prostate-endocr-rev-2004","paper-androgen-receptor-prostate-nat-rev-cancer-2015","paper-androgen-receptor-prostate-acta-pharmacol-sin-2015"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"An AR degrader or N-terminal-domain agent active against AR-V7 produces PSA responses in AR-V7-positive castration-resistant prostate cancer, where the response rate to further AR-pathway inhibition is near zero.","rationale":"AR-V7 is a well-defined, biomarker-selectable population with a mechanistically obvious unmet need; the degrader modality directly bypasses the missing ligand pocket.","test":"Phase 1b enriched for AR-V7-positive patients by circulating tumour cell assay, with PSA response rate and paired biopsy AR degradation as endpoints.","maturity":"preclinical-evidence","actor":"industry","cost":"medium","horizonYears":5},{"id":"idea-bio1-cfrna-plasticity-tracking","kind":"idea","name":"Detect tumours changing cell type from RNA in the blood","aka":[],"tldr":"Some cancers escape treatment by changing into a different kind of cell that the drug no longer affects. Tumour RNA in blood could show this shift months before a biopsy would.","summary":"Lineage plasticity (adenocarcinoma to small cell or neuroendocrine transformation in EGFR-mutant lung and prostate cancer) is a DNA-invisible resistance mechanism, usually diagnosed by biopsy late. Cell-free RNA and nucleosome footprinting can infer transcriptional state from plasma. The proposal is a plasma neuroendocrine transformation score monitored in patients at genetic risk (RB1 and TP53 loss) so that the switch to platinum-etoposide or a DLL3 bispecific is made early.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Tumour heterogeneity and clonal evolution): Gerlinger et al., Intratumor heterogeneity and branched evolution (NEJM 2012)","url":"https://doi.org/10.1056/NEJMoa1113205"}],"tags":[],"related":["prostate-roadmap","idea-prostate-plasticity-surveillance-before-it-is-neuroendocrine"],"cancers":["nsclc","prostate","sclc"],"sections":[],"technologies":["liquid-biopsy","rna-seq"],"targets":["dll3","tp53"],"drugs":["tarlatamab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-tumor-heterogeneity","b-resistance"],"keyPapers":["paper-vogelstein-surfing-p53-network-nature-2000"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A plasma-derived lineage score rises at least three months before histological confirmation of neuroendocrine transformation and enables an earlier treatment switch that improves survival in this subgroup.","rationale":"Transformation is frequent in RB1/TP53-altered EGFR-mutant and castration-resistant disease; cfDNA fragmentomics has already discriminated neuroendocrine from adenocarcinoma prostate cancer in small studies.","test":"Serial plasma in 200 RB1/TP53-altered patients on TKI or androgen-receptor therapy, blinded scoring, comparison with clinically indicated biopsies.","maturity":"speculative","actor":"research","cost":"medium","horizonYears":4},{"id":"idea-bio2-paediatric-first-development","kind":"idea","name":"Develop drugs in children first when the target is a children's target","aka":[],"tldr":"Children wait years for drugs because adult trials come first, even when the target belongs to a childhood cancer. Some drugs should start with children.","summary":"Paediatric oncology drug development is usually a downstream obligation, with paediatric plans triggered by adult programmes. For fusion-driven and developmental-lineage targets such as ALK in neuroblastoma, NTRK fusions, H3K27M-altered glioma and specific sarcoma fusions, the disease biology is paediatric and adult data add little. A paediatric-first pathway with matched incentives would compress timelines by years.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Rare and paediatric cancers without markets): Gatta et al., Rare cancers are not so rare: the rare cancer burden in Europe (EJC 2011)","url":"https://doi.org/10.1016/j.ejca.2011.08.008"}],"tags":[],"related":[],"cancers":["neuroblastoma","sarcoma","glioblastoma","all-leukemia"],"sections":[],"technologies":[],"targets":[],"drugs":["tovorafenib","dordaviprone","lorlatinib"],"companies":["childrens-oncology-group"],"institutions":[],"pathways":[],"terms":["h3k27m","gene-fusion","tumour-agnostic"],"trials":[],"people":["stefan-pfister","angelika-eggert","olivier-delattre"],"bottlenecks":["b-rare-cancers","b-regulatory-fragmentation","b-incentive-misalignment"],"keyPapers":["paper-gatta-eur-j-cancer"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"For targets whose prevalence is predominantly paediatric, a paediatric-first development pathway reaches approval three to five years earlier than the current adult-first sequence, without compromising safety characterisation.","rationale":"Tumour-agnostic approvals for NTRK inhibitors and the RACE for Children Act both show that paediatric-relevant development can be accelerated when the target biology justifies it. Precocious approvals in paediatric-specific diseases exist in other therapeutic areas.","test":"Identify targets with predominantly paediatric prevalence from genomic databases, then negotiate one paediatric-first development plan with a regulator and sponsor as a demonstration case.","maturity":"speculative","actor":"regulator","cost":"medium","horizonYears":7},{"id":"idea-fund-ablation-versus-surgery-trials","kind":"idea","name":"Device-agnostic public trials of ablation technologies against surgery","aka":[],"tldr":"Focused ultrasound, histotripsy, heat and electric-field ablation can destroy tumours without an incision, but each maker runs its own small study. Publicly-funded trials would compare them fairly against surgery.","summary":"A public trials programme comparing non-invasive and minimally invasive ablation (histotripsy, high-intensity focused ultrasound, microwave and radiofrequency ablation, irreversible electroporation) with surgical resection in indications where ablation is plausible: small hepatocellular carcinoma and liver metastases, small renal masses, localised prostate cancer, early pancreatic tumours in inoperable patients, and thyroid nodules. Trials are device-agnostic within a class, use oncological and functional co-primary endpoints, and are run by the surgical and interventional trials network. Manufacturers contribute devices and training but do not control design or data. Regulatory clearance of these devices has largely rested on technical success, not comparative cancer outcomes.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Surgery and radiotherapy cure most, get least): Sullivan et al., Global cancer surgery (Lancet Oncology Commission 2015)","url":"https://doi.org/10.1016/S1470-2045(15)00223-5"}],"tags":[],"related":["idea-fund-surgical-trials-network","idea-fund-device-technique-registry"],"cancers":["hcc","rcc","prostate","thyroid"],"sections":[],"technologies":["hifu-histotripsy","thermal-ablation","irreversible-electroporation"],"targets":[],"drugs":[],"companies":["histosonics","insightec"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-surgery-radiation-innovation","b-toxicity-qol"],"keyPapers":["paper-sullivan-lancet-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Within five years the programme delivers randomised evidence in at least three indications on whether ablation achieves non-inferior local control and survival with better functional outcomes than resection, and at least one result changes guidelines.","rationale":"Trials such as COLLISION (thermal ablation versus resection for colorectal liver metastases) show that randomising ablation against surgery is feasible and informative; histotripsy and HIFU have reached the clinic with single-arm evidence only. Device-agnostic public trials are the only way to obtain comparative evidence companies will not fund.","test":"Launch two randomised trials (liver and kidney) with device-agnostic ablation arms and track accrual, local control and functional outcomes.","maturity":"early-clinical","actor":"research","cost":"large","horizonYears":5},{"id":"idea-reg-ai-process-control-cell-manufacturing","kind":"idea","name":"Digital batch records and AI process control to halve cell therapy batch failures","aka":[],"tldr":"Autologous cell therapy batches fail more often than any other medicine because each patient's starting cells behave differently and the process runs without feedback. Inline sensors for metabolites, cell counts and cytokines, feeding models that adjust feeding and harvest timing in real time, could rescue batches that would otherwise be discarded.","summary":"Autologous manufacturing has out-of-specification and failure rates far above those of conventional biologics, driven by variable starting material and largely open-loop processes. Inline sensors (metabolites, cell counts, imaging, cytokines), electronic batch records and machine-learning models predicting final yield and potency from early process data allow adaptive feeding, harvest timing and early re-manufacture decisions. The proposal is a shared, anonymised dataset of manufacturing runs across manufacturers and an open model benchmark, with regulatory guidance on adaptive control within a validated design space.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Manufacturing cost and time for living and radioactive medicines): Hernandez, Prasad & Gellad, Total costs of chimeric antigen receptor T-cell immunotherapy (JAMA Oncology 2018)","url":"https://doi.org/10.1001/jamaoncol.2018.0977"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["car-t","til-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-manufacturing-cell-therapy","b-ai-validation"],"keyPapers":["paper-hernandez-jama-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Adaptive control informed by shared run data reduces manufacturing failure rates by at least half and the coefficient of variation in transduced cell dose by a third, without any change in clinical safety.","rationale":"Process analytical technology and design-space approaches transformed small-molecule and biologic manufacturing; cell therapy is the modality with the most variability and therefore the most to gain, and every run already generates the data.","test":"Pool de-identified process data from at least three manufacturers, build predictive models of failure, then run a prospective study using model-guided interventions on 200 batches versus standard operation.","maturity":"preclinical-evidence","actor":"engineering","cost":"medium","horizonYears":3},{"id":"idea-data-digital-twin-predict-then-observe","kind":"idea","name":"Digital twins for treatment selection, validated by predicting before observing","aka":[],"tldr":"Build a computer model of each patient's cancer that forecasts how it will respond to each treatment option, and prove it by writing the forecast down before the real result is known.","summary":"Patient digital twins (mechanistic, statistical or hybrid models of a patient's tumour and physiology) are proposed for treatment selection, but validation is almost entirely retrospective. The proposal is a validation programme with a strict protocol: for each enrolled patient, the twin's prediction (response, progression time, toxicity) for the chosen treatment is locked before treatment; predictions are compared with observed outcomes; calibration and discrimination are published. Only twins that pass proceed to trials where predictions inform choices.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (AI that is built but not validated or deployed): Wu et al., How medical AI devices are evaluated: limitations and recommendations from an analysis of FDA approvals (Nature Medicine 2021)","url":"https://doi.org/10.1038/s41591-021-01312-x"}],"tags":[],"related":["idea-multimodal-foundation-model"],"cancers":[],"sections":["ai-computation"],"technologies":["organoids","functional-drug-testing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-ai-validation","b-tumor-heterogeneity"],"keyPapers":["paper-wu-nat-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Prospectively locked twin predictions will achieve clinically useful calibration for at least one common decision (for example, response to first-line chemo-immunotherapy in NSCLC), and a randomised trial of twin-informed selection will improve response rates.","rationale":"Weather and engineering models earned trust through routine, scored forward prediction; medical models have skipped this step and are trusted or dismissed on retrospective fits.","test":"Enrol 500 patients across two cancers; lock predictions; publish calibration plots and Brier scores; proceed to a randomised trial only if pre-specified thresholds are met.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":4},{"id":"idea-data-national-slide-archive","kind":"idea","name":"Digitise the nation's pathology slides and link them to outcomes","aka":[],"tldr":"Scan the millions of cancer slides already sitting in hospital basements and connect each to what happened to the patient, creating the world's largest training set for pathology AI.","summary":"Pathology departments hold decades of glass slides with matched registry outcomes. Digitising them at scale (tens of millions of slides) and linking to registry survival, treatment and recurrence data would create a public resource that dwarfs any commercial pathology AI training set. Precedents include the PathLAKE and iCAIRD centres in the UK, the TCGA image collection, and the NHS digital pathology programme. Cost is dominated by scanning and storage, both of which have fallen sharply.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Data silos): AACR Project GENIE","url":"https://www.aacr.org/professionals/research/aacr-project-genie/"}],"tags":[],"related":["tcga-gdc"],"cancers":[],"sections":["ai-computation"],"technologies":["digital-pathology-ai","pathology-foundation-model","histopathology-ihc"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-data-silos","b-ai-validation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A linked archive of more than 10 million slides with outcomes, released under governed access, will produce prognostic and predictive pathology models that outperform current commercial models on external validation within three years of release.","rationale":"Foundation models scale with data; the best current pathology models were trained on around one to three million slides from single institutions. Public linked data would also allow independent validation, which is what commercial models lack.","test":"Fund one region to scan 500,000 archival slides linked to registry outcomes; release under a TRE; run an open benchmark against existing models for five-year survival prediction in three cancers.","maturity":"early-clinical","actor":"philanthropy","cost":"large","horizonYears":4},{"id":"idea-tr1-esource-ehr-to-edc","kind":"idea","name":"Direct record-to-database data capture: no manual transcription, no full source verification","aka":[],"tldr":"Trial staff still retype data from the hospital record into the trial database, and monitors then check every entry by hand. Piping data directly and checking by risk would cut cost and errors.","summary":"Structured EHR data (labs, vitals, medications, imaging reports, deaths) flow into the trial database via FHIR-based eSource interfaces with audit trails; source data verification is replaced by risk-based and statistical monitoring, as permitted by ICH E6(R3). Requires standardised oncology data elements (mCODE) and vendor cooperation.","asOf":"2026-09-08","links":[{"label":"CDISC standards","url":"https://www.cdisc.org/"},{"label":"mCODE","url":"https://mcodeinitiative.org/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["ai-trial-matching"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-design","b-data-silos"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"eSource trials will reduce data management and monitoring cost per patient by at least 30 percent and reduce transcription errors, with equivalent or better data quality on audit.","rationale":"Manual transcription is the largest source of trial data error and monitoring is the largest single cost line; both are artefacts of paper-era processes. Other regulated industries moved to direct data capture decades ago.","test":"Run one cooperative-group trial with eSource at half its sites and conventional capture at the rest; compare cost, query rates and audit findings.","maturity":"early-clinical","actor":"engineering","cost":"medium","horizonYears":3},{"id":"idea-reg-rd-cost-disclosure-condition","kind":"idea","name":"Disclose R&D and manufacturing costs of publicly funded cancer drugs to get coverage","aka":[],"tldr":"Taxpayers fund much of the science behind new cancer drugs but never learn what they cost to develop. Disclosure should be a condition of public payment.","summary":"The WHA 2019 transparency resolution called for disclosure of R&D costs and public funding, but implementation has been minimal. Many oncology drugs originate in publicly funded research (NIH, CRUK, national academic centres). The proposal is that public payers require, as a condition of coverage for any oncology drug that received public research funding or tax credits, audited disclosure of clinical development costs, manufacturing cost of goods and public contributions, published in a standard format and used as one input to price negotiations.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Prices and value): Prasad, De Jesús & Mailankody, The high price of anticancer drugs: origins, implications, barriers, solutions (Nat Rev Clin Oncol 2017)","url":"https://doi.org/10.1038/nrclinonc.2017.31"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["nci","cruk"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-drug-pricing","b-incentive-misalignment"],"keyPapers":["paper-prasad-nat-rev-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Disclosure requirements are followed by lower launch price growth for disclosed products relative to non-disclosed products in the same markets and by public support for reinvestment conditions on publicly funded discoveries.","rationale":"Negotiation over price without knowledge of cost is negotiation in the dark; audited cost disclosure is routine for public procurement in defence and infrastructure, and public funding creates a legitimate claim to it.","test":"Adopt the requirement in one country for oncology products launched over three years; assess compliance, disclosed figures and price trajectories against other countries.","maturity":"speculative","actor":"policy","cost":"small","horizonYears":4},{"id":"idea-tr1-diversity-plans-with-consequences","kind":"idea","name":"Diversity action plans with consequences: unmet targets trigger post-approval requirements","aka":[],"tldr":"Companies now have to file a plan for enrolling a representative mix of patients. If the trial misses the plan, the label should say so and the company should be required to fill the gap after approval.","summary":"Under the US FDORA requirement for diversity action plans, sponsors set enrolment goals by race, ethnicity, sex and age. The proposal adds teeth: the approved label states enrolled demographics against disease incidence; shortfalls beyond a threshold trigger a post-marketing requirement for a supplementary study or registry in the under-enrolled group with a deadline; and repeat shortfalls are published in an annual sponsor scorecard.","asOf":"2026-09-08","links":[{"label":"FDA: Clinical trial diversity (archived copy)","url":"https://web.archive.org/web/20250201021950/https://www.fda.gov/consumers/minority-health-and-health-equity/clinical-trial-diversity"},{"label":"FDA Drug Trials Snapshots","url":"https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trials-snapshots"}],"tags":[],"related":["fda-approvals"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["nci"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-diversity"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Attaching label statements and post-marketing requirements to missed diversity targets will raise representativeness of pivotal trials, measured by participation-to-prevalence ratios in FDA Drug Trials Snapshots, within five years.","rationale":"Goals without consequences have not moved enrolment demographics much over two decades. Post-marketing requirements are an existing, enforceable instrument.","test":"Compare participation-to-prevalence ratios for approvals before and after enforcement begins, and track completion of triggered post-marketing studies.","maturity":"being-tested-at-scale","actor":"regulator","cost":"small","horizonYears":3},{"id":"idea-tr1-patient-reported-toxicity-dose-algorithms","kind":"idea","name":"Dose adjustments driven by patients' own symptom reports, tested against clinician judgement","aka":[],"tldr":"Patients report symptoms on their phone each week; a set of rules turns severe or worsening symptoms into a dose hold or reduction before the next clinic visit. This could keep people on treatment longer and feeling better.","summary":"Protocolised dose-modification algorithms triggered by weekly PRO-CTCAE reports (with nurse review), compared in a randomised trial with standard clinician-assessed dose modification at scheduled visits. Builds on the randomised evidence that symptom monitoring with alerts improved QoL and survival in chemotherapy patients, extending it to dosing decisions for oral agents.","asOf":"2026-09-08","links":[{"label":"PRO-CTCAE (NCI)","url":"https://healthcaredelivery.cancer.gov/pro-ctcae/"},{"label":"Symptom monitoring with patient-reported outcomes during routine cancer treatment (JAMA 2017)","url":"https://jamanetwork.com/journals/jama/fullarticle/2630810"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["kinase-inhibitors"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-dose-optimisation","b-toxicity-qol","b-patient-voice"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"PRO-driven dose algorithms will reduce grade 3+ toxicity and unplanned hospital visits while increasing time on treatment and non-inferior PFS compared with visit-based dose management.","rationale":"Clinicians under-detect and under-grade symptoms relative to patients; toxicity that is caught early can be managed with a dose hold rather than a permanent reduction or discontinuation.","test":"A randomised trial across community oncology practices for patients starting oral targeted therapy, PRO-driven algorithm versus usual care, with time on treatment and grade 3+ toxicity as co-primaries.","maturity":"early-clinical","actor":"clinic","cost":"small","horizonYears":3},{"id":"idea-tr1-adc-dose-and-schedule-optimisation","kind":"idea","name":"Dose and schedule optimisation trials specific to antibody-drug conjugates","aka":[],"tldr":"Antibody-drug conjugates deliver chemotherapy payloads into tumours but cause lung, eye and nerve damage that tracks total exposure, and several were approved without an optimised dose. Randomised comparisons of lower doses, longer intervals and capped cumulative payload could keep the benefit while cutting these harms.","summary":"Randomised dose and schedule comparisons for ADCs (e.g., lower dose per cycle, extended intervals, capped cumulative payload dose, response-adapted de-escalation) with PK of conjugate and free payload, tolerability estimands (ILD, ocular toxicity, neuropathy) and efficacy. The 5.4 versus 6.4 mg/kg trastuzumab deruxtecan comparison and dose modifications for several approved ADCs show dose was not optimised at approval.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Wrong doses): FDA Oncology Center of Excellence, Project Optimus","url":"https://www.fda.gov/about-fda/oncology-center-excellence/project-optimus"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["adc"],"targets":[],"drugs":["trastuzumab-deruxtecan","enfortumab-vedotin","mirvetuximab-soravtansine","sacituzumab-govitecan"],"companies":[],"institutions":[],"pathways":[],"terms":["ild","payload","dar"],"trials":[],"people":[],"bottlenecks":["b-dose-optimisation","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Optimised ADC dosing will reduce grade 2+ exposure-driven toxicities by a third and discontinuation rates substantially, with non-inferior efficacy, for most ADCs tested.","rationale":"ADC toxicity is largely payload-exposure-driven and cumulative, while efficacy depends on target saturation that occurs at lower doses; the therapeutic window is being wasted by MTD-based dosing.","test":"Two randomised phase 2/3 dose-comparison trials of approved ADCs with high discontinuation rates, with tolerability co-primary and efficacy non-inferiority.","maturity":"early-clinical","actor":"industry","cost":"medium","horizonYears":3},{"id":"idea-bio2-lean-mass-dosing","kind":"idea","name":"Dose chemotherapy by muscle mass, not body surface area","aka":[],"tldr":"Chemotherapy doses are calculated from height and weight, a formula from the 1950s. Doses based on actual muscle mass may cause fewer severe side-effects.","summary":"Body surface area poorly predicts clearance for most cytotoxics, and low lean body mass is associated with markedly higher rates of severe toxicity at standard doses, above all with fluoropyrimidines and taxanes. Lean mass is now measurable automatically from routine imaging, making an alternative dosing metric practical for the first time.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Cachexia, toxicity and the limits of the patient): Fearon et al., Definition and classification of cancer cachexia (Lancet Oncology 2011)","url":"https://doi.org/10.1016/S1470-2045(10)70218-7"}],"tags":[],"related":[],"cancers":["colorectal","breast-hr-positive"],"sections":[],"technologies":["cytotoxic-chemotherapy","radiology-ai-screening","ct"],"targets":[],"drugs":["capecitabine-temozolomide","paclitaxel","docetaxel"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-cachexia-supportive","b-dose-optimisation","b-toxicity-qol"],"keyPapers":["paper-fearon-lancet-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Lean-mass-based dosing reduces grade 3 or higher toxicity by a third compared with body surface area dosing, without reducing dose intensity delivered per unit of lean tissue or compromising efficacy.","rationale":"Drug clearance tracks metabolically active tissue rather than total body size, which explains why sarcopenic patients are effectively overdosed. Pharmacogenomic dose adjustment for DPYD has already established that toxicity-driven dose individualisation is acceptable to clinicians and regulators.","test":"A randomised trial in one regimen with a high toxicity rate, comparing lean-mass dosing with standard dosing; primary endpoint severe toxicity, with pharmacokinetic sampling to confirm the mechanism.","maturity":"speculative","actor":"clinic","cost":"medium","horizonYears":5},{"id":"idea-tr1-geriatric-dose-finding-cohorts","kind":"idea","name":"Dose-finding in older and frail patients, not extrapolation from fit ones","aka":[],"tldr":"The dose for a frail 80-year-old is guessed from what fit 55-year-olds tolerated. Running dose-finding in older patients directly, using frailty assessment, would give doses they can actually take.","summary":"Dedicated dose-finding and dose-comparison cohorts in patients aged 75 and over or with frailty on geriatric assessment, run in parallel with or after the main dose-finding, using tolerability, function and QoL alongside efficacy. The GO2 trial in advanced oesophago-gastric cancer showed that reduced-intensity chemotherapy in frail and older patients was non-inferior with better QoL, demonstrating the approach.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Wrong doses): FDA Oncology Center of Excellence, Project Optimus","url":"https://www.fda.gov/about-fda/oncology-center-excellence/project-optimus"}],"tags":[],"related":[],"cancers":["gastric","esophageal","aml"],"sections":[],"technologies":["geriatric-assessment","cytotoxic-chemotherapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-dose-optimisation","b-aging-comorbidity"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Frailty-stratified dose finding will define lower recommended doses for frail patients for most agents studied, with non-inferior disease control and better patient-reported outcomes than label dosing.","rationale":"Pharmacokinetics, organ reserve and tolerance differ with age and frailty; real-world discontinuation in older patients is high, and a 'start full dose and reduce' approach loses patients early.","test":"Embed a frailty-stratified dose cohort in three new-agent programmes and one randomised reduced-dose trial in a frail population per year, tracking label statements and outcomes.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":3},{"id":"idea-net-dosimetry-prrt","kind":"idea","name":"Dosimetry-personalised PRRT instead of four fixed cycles","aka":[],"tldr":"Measure the radiation each patient's tumour and kidneys actually absorb and adjust the number and size of doses, instead of giving everyone four identical cycles.","summary":"The idea is to personalise peptide receptor radionuclide therapy with lutetium-177 dotatate or 177Lu-edotreotide by measuring the radiation each patient's tumour, kidneys and marrow actually absorb on SPECT/CT after each cycle, and adjusting the number and size of doses. The standard of 7.4 GBq for four cycles leaves many patients under-dosed relative to renal and marrow limits, uptake varies widely, and retrospective dosimetry shows tumour absorbed dose correlates with response. The hypothesis is that dosimetry-guided PRRT raises cumulative tumour dose and response rate without exceeding organ limits. The test is a randomised phase 2 of individualised versus fixed activity; P-PRRT in Canada is already testing this, and the idea addresses the wrong-doses bottleneck.","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT03049189: COMPETE","url":"https://clinicaltrials.gov/study/NCT03049189"}],"tags":[],"related":[],"cancers":["neuroendocrine"],"sections":[],"technologies":["prrt","spect"],"targets":[],"drugs":["lutathera","itm-11"],"companies":[],"institutions":[],"pathways":[],"terms":["dosimetry"],"trials":["compete","nct03972488","nct04919226","netter-1"],"people":[],"bottlenecks":[],"keyPapers":["paper-lutetium-177-dotatate-neuroendocrine-pract-radiat-oncol-2022"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Dosimetry-guided PRRT increases cumulative tumour dose and response rate without exceeding renal/marrow limits, versus fixed dosing.","rationale":"Wide inter-patient variation in uptake; SPECT/CT after each cycle makes dosimetry feasible.","test":"Randomised phase 2 of individualised vs fixed activity with ORR and PFS endpoints.","maturity":"early-clinical"},{"id":"idea-moon-task-shifting-ai-oncology-capacity","kind":"idea","name":"Double oncology capacity in low-resource settings with task-shifting and AI decision support","aka":[],"tldr":"Many countries have one oncologist for millions of people. Train nurses and general doctors to deliver protocolised cancer care with software checks and remote specialist oversight.","summary":"Workforce shortages, not drugs, cap cancer treatment in much of Africa and South Asia. Task-shifting with decision support scaled HIV treatment; oncology has pilots (nurse-led chemotherapy, Botswana and Rwanda models, tele-oncology networks). The proposal is a package: protocol-driven regimens for the commonest cancers, a decision-support and safety-check tool validated for use by non-specialists, remote tumour board review, structured training and certification, and outcome registries to monitor safety and quality.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Not enough oncologists, nurses, pathologists, physicists): Yang et al., Projected supply of and demand for oncologists and radiation oncologists through 2025 (JOP 2014)","url":"https://doi.org/10.1200/JOP.2013.001319"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["tata-memorial"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-workforce","b-global-access","b-ai-validation"],"keyPapers":["paper-yang-j-oncol-pract"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Task-shifted, AI-supported care delivers guideline-concordant treatment with toxicity and survival outcomes non-inferior to specialist-delivered care and treats twice as many patients per oncologist.","rationale":"Most cancer care is protocolised and the risk lies in omissions and dose errors, which software and remote oversight catch reliably.","test":"Stepped-wedge implementation in district hospitals in two countries with treatment completion, protocol adherence, severe toxicity and one-year survival as endpoints compared with specialist centres.","maturity":"early-clinical","actor":"policy","cost":"large","horizonYears":5},{"id":"idea-bio1-lytac-surface-degraders","kind":"idea","name":"Drag cancer's surface and secreted proteins to the cell's recycling bin","aka":[],"tldr":"Some cancer proteins sit on the cell surface or float outside cells, where protein-destroying drugs cannot reach. A different trick can drag them inside to be broken down.","summary":"Lysosome-targeting chimeras (LYTACs) and antibody-based equivalents (KineTACs) use receptors such as the cation-independent mannose-6-phosphate receptor or ASGPR to internalise and degrade extracellular and membrane proteins. Cancer targets that resist antibody blockade because they are shed, recycled or in excess (for example growth factors, immunosuppressive ligands, and non-internalising surface antigens) become tractable.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The undruggable drivers): Dang et al., Drugging the 'undruggable' cancer targets (Nature Reviews Cancer 2017)","url":"https://doi.org/10.1038/nrc.2017.36"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["protac-degrader","monoclonal-antibody"],"targets":[],"drugs":[],"companies":[],"institutions":["stanford"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-undruggable-targets","b-tme-immunosuppression"],"keyPapers":["paper-dang-nat-rev-cancer"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"LYTAC-mediated removal of a shed immunosuppressive ligand from the tumour microenvironment restores T-cell infiltration and improves checkpoint inhibitor efficacy in a syngeneic model more than a blocking antibody alone.","rationale":"Degradation removes protein rather than occupying it, which matters where ligand is continuously produced. The chemistry has been demonstrated for several model targets in cells and mice.","test":"Build a LYTAC against one shed ligand with established immunosuppressive function, compare with a blocking antibody in matched syngeneic tumours, and measure ligand levels and T-cell infiltration.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":7},{"id":"idea-tr1-drop-non-essential-biopsies","kind":"idea","name":"Drop mandatory fresh biopsies where blood or archival tissue would do","aka":[],"tldr":"Trials often require a fresh tumour biopsy just to enter, even when the sample is only for research. Classifying each biopsy as essential or research-only, making the latter optional and allowing blood tests or archived tissue for eligibility markers, would remove a painful hurdle that drives refusals.","summary":"Protocols classify each biopsy as essential (eligibility-defining, no alternative) or research-only; research-only biopsies become optional sub-studies, and eligibility biomarkers may be assessed on archival tissue or ctDNA where analytically validated. Screen-failure and refusal attributable to biopsy requirements are tracked and published.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Trials enrol too few, too slowly): Unger et al., Systematic review of barriers to cancer trial participation (JNCI 2019)","url":"https://doi.org/10.1093/jnci/djy221"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["liquid-biopsy","cgp"],"targets":[],"drugs":[],"companies":["guardant-health","foundation-medicine"],"institutions":[],"pathways":[],"terms":["ctdna"],"trials":[],"people":[],"bottlenecks":["b-trial-enrolment","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Removing mandatory research biopsies will reduce screen failure and refusal rates by a measurable margin and shorten time to enrolment, without loss of the biomarker data needed for the primary analysis.","rationale":"Mandatory biopsies are among the most frequently cited reasons patients decline early-phase trials, and a notable share of biopsies yield insufficient tissue. Liquid biopsy now matches tissue for many actionable alterations.","test":"A sponsor amends a set of ongoing trials to make research biopsies optional and compares screen failure, refusal and enrolment speed before and after amendment.","maturity":"early-clinical","actor":"industry","cost":"small","horizonYears":1},{"id":"idea-tr1-language-access-in-trials","kind":"idea","name":"Drop the 'must speak English' rule: translated consent and questionnaires as standard","aka":[],"tldr":"Trials quietly exclude people who do not speak the local language because consent forms and questionnaires exist only in that language. Sponsors should provide validated translations for any language spoken by at least 5 percent of the catchment and fund interpreters; translations of common instruments already exist for dozens of languages.","summary":"Protocols may not exclude on language; sponsors provide certified translations of consent and patient-reported outcome instruments in the languages spoken by at least 5 percent of the catchment population (with linguistically validated PRO versions), and fund professional interpreters for visits. Validated translations of common PRO instruments already exist for dozens of languages.","asOf":"2026-09-08","links":[{"label":"EORTC Quality of Life Group (translated instruments)","url":"https://qol.eortc.org/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["curie-nki-eortc"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-diversity","b-trial-enrolment"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Removing language exclusions and funding translations will increase enrolment of non-native-speaking patients to their share of the catchment population and will not reduce PRO completion rates.","rationale":"Language exclusions are common and rarely justified scientifically; PRO instruments have validated versions in many languages, so the cost is coordination rather than development.","test":"Audit a sample of protocols for language exclusions; sponsor pilot removing them at multilingual sites and compare enrolment by language.","maturity":"early-clinical","actor":"industry","cost":"small","horizonYears":1},{"id":"idea-cost-interchangeable-oncology-biosimilars","kind":"idea","name":"Drop the extra switching studies for interchangeable oncology biosimilars","aka":[],"tldr":"US law lets a pharmacist swap an 'interchangeable' biosimilar without asking the prescriber, but earning that label used to need costly switching studies; the FDA now says those are usually unnecessary, which should be made permanent for cancer antibodies.","summary":"Interchangeability is a US-only regulatory status that allows pharmacy-level substitution. Historically it required dedicated switching studies, which delayed and added cost to biosimilar programmes. In 2024 the FDA issued draft guidance stating that switching studies are generally not needed to demonstrate interchangeability. Finalising that position and applying it to the oncology antibodies would remove a barrier to automatic substitution in the 40-plus states whose pharmacy laws recognise the status.","asOf":"2026-09-10","links":[{"label":"FDA: Biosimilars","url":"https://www.fda.gov/drugs/therapeutic-biologics-applications-bla/biosimilars"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["fda-oce","ema"],"pathways":[],"terms":["biosimilar"],"trials":[],"people":[],"bottlenecks":["b-drug-pricing","b-regulatory-fragmentation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Interchangeable designation for oncology biosimilars without switching studies will bring at least three interchangeable cancer antibodies to market within three years and raise substitution rates in states with pharmacy substitution laws.","rationale":"European regulators regard all approved biosimilars as interchangeable and have a decade of switching data without safety signals.","test":"Track interchangeable designations, time to designation and biosimilar share in oncology before and after the guidance is finalised.","maturity":"early-clinical","actor":"regulator","cost":"small","horizonYears":2},{"id":"idea-tr2-label-assay-concordance","kind":"idea","name":"Drug labels must state which biomarker assays were validated and how they compare","aka":[],"tldr":"A drug label says 'for PD-L1 positive patients' but does not say that other tests give different answers. Labels should list the validated tests and how much they disagree.","summary":"Labels reference the companion diagnostic used in the pivotal trial but not the performance of other assays commonly used in practice, leaving clinicians to guess whether their laboratory's test is equivalent. Requiring a structured concordance section (validated assays, concordance data with other widely used assays, known discordant regions) would surface the uncertainty and drive sponsors to generate bridging data.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Biomarkers are not validated or standardised): Fernandez et al., Examination of low ERBB2 protein expression in breast cancer tissue (JAMA Oncology 2022)","url":"https://doi.org/10.1001/jamaoncol.2021.7239"}],"tags":[],"related":["fda-approvals","idea-tr2-pdl1-digital-calibration"],"cancers":[],"sections":[],"technologies":["companion-diagnostic"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["companion-diagnostic-term"],"trials":[],"people":[],"bottlenecks":["b-biomarker-validation","b-knowledge-diffusion"],"keyPapers":["paper-fernandez-jama-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Labels with concordance sections will be followed by an increase in published bridging studies and a reduction in the use of unvalidated assay substitutions, measurable in laboratory surveys.","rationale":"Clinicians substitute assays in practice for cost and availability reasons; the risk of that substitution is currently invisible in the primary document they consult.","test":"Draft the section for five biomarker-restricted labels using existing concordance literature; survey clinicians and laboratories on utility; propose as a labelling requirement.","maturity":"speculative","actor":"regulator","cost":"small","horizonYears":2},{"id":"idea-dual-payload-first","kind":"idea","name":"Dual-payload ADCs in first line to prevent resistance","aka":[],"tldr":"Rather than waiting for resistance to one payload and then switching, give two mechanisms from day one, as HIV therapy does.","summary":"Rather than waiting for resistance to one payload and then switching, this idea gives two payload mechanisms from day one, as HIV therapy does. A TOP1 plus tubulin or TOP1 plus DNA-crosslinker dual-payload TROP2 or HER2 ADC is expected to outperform a single-payload ADC in first-line metastatic breast cancer at equivalent toxicity, because combination therapy prevents selection of resistant clones and dual-payload ADCs achieve this without doubling antibody dose. ACR335 and the Sutro and Mersana programmes show manufacturability. The test is phase 1 dose-finding then a randomised phase 2 against a single-payload ADC. Speculative in maturity, it addresses the bottlenecks Acquired resistance to every therapy and Too many combinations to test.","asOf":"2026-09-04","links":[{"label":"Yamazaki et al., Antibody-drug conjugates with dual payloads for combating breast tumour heterogeneity and drug resistance (Nature Communications 2021)","url":"https://doi.org/10.1038/s41467-021-23793-7"}],"tags":[],"related":["idea-payload-switching"],"cancers":["tnbc","breast-hr-positive"],"sections":[],"technologies":["dual-payload-adc","adc","site-specific-conjugation"],"targets":["trop2","her2"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-yarden-sliwkowski-erbb-network-nrmcb-2001","paper-yamazaki-nat-commun"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A TOP1 + tubulin (or TOP1 + DNA-crosslinker) dual-payload TROP2 or HER2 ADC produces longer PFS in first-line metastatic breast cancer than a single-payload ADC at equivalent toxicity.","rationale":"Orthogonal resistance mechanisms; ACR335 and Sutro/Mersana programmes demonstrate manufacturability.","test":"Phase 1 dose-finding then randomised phase 2 vs single-payload ADC; monitor resistance biomarkers at progression.","maturity":"speculative"},{"id":"idea-data-dynamic-consent-app","kind":"idea","name":"Dynamic consent with usage receipts","aka":[],"tldr":"An app where patients choose what their data can be used for, see every time it is used, and can switch permissions on or off.","summary":"Dynamic consent replaces the one-off paper form with an ongoing digital relationship: granular preferences (commercial use, genomic data, contact for trials), notifications when data are used, and revocation that propagates to data holders. Pilots in Australia (CTRL platform) and rare-disease registries have shown feasibility. The oncology-specific version adds automatic trial-matching alerts as a return of value to the patient.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Data silos): AACR Project GENIE","url":"https://www.aacr.org/professionals/research/aacr-project-genie/"}],"tags":[],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":["ai-trial-matching"],"targets":[],"drugs":[],"companies":["patient-data-vault"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-data-silos","b-patient-voice"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Patients given dynamic consent will permit broader use (more categories ticked) and remain enrolled longer than patients under static broad consent, because transparency and reciprocity increase trust.","rationale":"Trust, not privacy law, is what limits sharing; usage receipts turn an abstract promise into a verifiable one. Rare-disease cohorts using dynamic consent report higher retention.","test":"Randomise consecutive patients at two centres to static broad consent versus a dynamic consent app; compare permission breadth, withdrawal at 12 months, and patient-reported trust.","maturity":"early-clinical","actor":"patients","cost":"small","horizonYears":2},{"id":"idea-acc-earmarked-palliative-budget-share","kind":"idea","name":"Earmark a fixed share of every national cancer budget for palliative care","aka":[],"tldr":"Most of the money in cancer goes to treatments that help a few people for a short time, while pain relief for the dying, which is cheap and works, gets almost nothing. Ring-fencing a small fixed share would change that.","summary":"Palliative care receives a tiny fraction of cancer spending in most countries despite reaching more patients per dollar than most therapies. A policy earmarking a minimum share (for example, 5%) of national cancer control budgets for palliative care, including morphine supply, workforce training, and community services, would guarantee a floor. Earmarking has drawbacks but is a proven way to protect neglected functions.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Pain relief and palliative care are unavailable to most): WHO fact sheet, Palliative care","url":"https://www.who.int/news-room/fact-sheets/detail/palliative-care"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-palliative","b-funding-allocation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Countries adopting an earmark will at least double palliative care coverage within four years, with the earmark spent rather than reallocated.","rationale":"Public health functions that lack a constituency are systematically underfunded; earmarks have protected immunisation and mental health budgets in similar situations.","test":"Track palliative expenditure, coverage, and morphine consumption in adopting versus non-adopting countries over five years.","maturity":"speculative","actor":"policy","cost":"medium","horizonYears":4},{"id":"idea-efflux-agnostic","kind":"idea","name":"Efflux-agnostic therapy for mesenchymal TNBC","aka":[],"tldr":"Some tumours pump out every drug. Use treatments the pumps cannot touch: radiation, radioligands, immune cells, and payloads designed to evade them.","summary":"Some tumours pump out every drug, so this idea treats mesenchymal or claudin-low TNBC and post-chemotherapy residual disease with modalities the pumps cannot touch: radiation, radioligands, T-cell engagers and ADCs whose payloads are not efflux substrates. Tumours with high ABCB1 or ABCG2 are expected to gain less from TOP1 or tubulin ADCs, since MMAE, DXd and SN-38 are all substrates, and more from radioimmunotherapy, engagers, degrader-antibody conjugates or sacituzumab tirumotecan. The test runs a retrospective ABCB1 and ABCG2 analysis of ASCENT and TROPION-Breast02 samples, prospective stratification in a TNBC ADC trial and payload comparisons in ABCG2-high PDX models. With preclinical evidence, it bears on the ADC technology and the efflux pump record.","asOf":"2026-09-04","links":[],"tags":[],"related":[],"cancers":["tnbc"],"sections":[],"technologies":["adc","radioimmunotherapy","t-cell-engager","degrader-antibody-conjugate"],"targets":[],"drugs":["sacituzumab-tirumotecan"],"companies":[],"institutions":[],"pathways":["emt"],"terms":["efflux-pump"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-nct05347134-nat-med-2025"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Tumours with high ABC transporter expression (RNA or IHC) derive less benefit from TOP1/tubulin ADCs and more from radioligand therapy, T-cell engagers, or ADCs with non-substrate payloads.","rationale":"Radiation and immune killing are not pumped out; sac-TMT's payload is reported to be a weaker efflux substrate; degrader payloads may also evade pumps.","test":"Retrospective ABCB1/ABCG2 analysis in ASCENT and TROPION-Breast02 samples; prospective stratification in a TNBC ADC trial; preclinical head-to-head of payloads in ABCG2-high PDX models.","maturity":"preclinical-evidence"},{"id":"idea-moon-eliminate-infection-cancers","kind":"idea","name":"Eliminate infection-caused cancers: HPV, hepatitis B and C, H. pylori and EBV","aka":[],"tldr":"About one in eight cancers is caused by an infection we can vaccinate against, cure or eradicate. A concerted global programme could make those cancers rare within a generation.","summary":"HPV vaccination and screening (WHO cervical elimination strategy), universal hepatitis B birth-dose vaccination, hepatitis C cure with direct-acting antivirals, Helicobacter pylori screen-and-treat (with randomised evidence of gastric cancer reduction) and an EBV vaccine now in early trials together address cancers responsible for millions of cases annually, concentrated in low- and middle-income countries. The proposal is a single financed elimination programme with country targets, pooled procurement, integrated delivery through existing immunisation and primary care platforms, and registry-based tracking of incidence.","asOf":"2026-09-08","links":[{"label":"WHO cervical cancer elimination initiative","url":"https://www.who.int/initiatives/cervical-cancer-elimination-initiative"},{"label":"Gavi","url":"https://www.gavi.org/"}],"tags":[],"related":[],"cancers":["cervical","hcc","gastric","head-and-neck"],"sections":[],"technologies":["hpv-vaccine"],"targets":[],"drugs":[],"companies":[],"institutions":["iarc"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption","b-global-access"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Coordinated delivery achieves WHO cervical elimination targets in participating countries and reduces the combined incidence of liver, gastric and cervical cancer by half by 2050.","rationale":"Every component has proven efficacy; the failure is organisational and financial. Elimination programmes for polio and measles show what coordinated financing achieves.","test":"Fund full-package implementation in five high-burden countries and compare cancer incidence trajectories against matched countries over ten years, with coverage metrics as leading indicators.","maturity":"being-tested-at-scale","actor":"policy","cost":"large","horizonYears":15},{"id":"idea-pdac-cachexia-trials-embedded-in-chemotherapy-trials","kind":"idea","name":"Embed cachexia treatment in chemotherapy trials: weight, muscle and treatment delivery as co-primary endpoints","aka":[],"tldr":"Most people with pancreatic cancer lose muscle and weight in a way food alone cannot reverse, and that wasting is a common reason chemotherapy is cut or stopped. A 2024 trial showed an antibody against the hormone GDF-15 restored weight and activity in twelve weeks, a third of the patients having pancreatic cancer. The proposal is to test it inside the chemotherapy trials, not alongside them.","summary":"Fearon's 2011 consensus defined cachexia as ongoing skeletal muscle loss not fully reversible by nutritional support, with weight loss over 5 percent (or over 2 percent with low body mass index or sarcopenia) as the diagnostic criterion and stages from pre-cachexia to refractory. Ponsegromab (Groarke 2024) in 187 patients with raised GDF-15 (32 percent pancreatic cancer) produced dose-dependent weight gain versus placebo of 1.22 to 2.81 kg at 12 weeks, with better appetite and measured physical activity at 400 mg and fewer adverse events than placebo. In pancreatic cancer specifically, cachexia and exocrine insufficiency (enzyme replacement reaching 21.7 percent of UK patients, Roberts 2019) determine whether patients receive and tolerate FOLFIRINOX-class regimens, yet cachexia trials are run in mixed-cancer populations with weight as the endpoint and chemotherapy trials exclude patients with significant weight loss. The proposal is a factorial or platform design in first-line pancreatic cancer: chemotherapy backbone with or without a GDF-15 antibody, with mandatory enzyme replacement and dietetic support in all arms, and co-primary endpoints of relative dose intensity delivered and lean mass at 12 weeks, with overall survival as the key secondary.","asOf":"2026-09-24","links":[{"label":"Groarke et al.: ponsegromab for cancer cachexia (NEJM 2024)","url":"https://europepmc.org/article/MED/39282907"},{"label":"Fearon et al.: definition and classification of cancer cachexia (Lancet Oncol 2011)","url":"https://europepmc.org/article/MED/21296615"},{"label":"ClinicalTrials.gov NCT05546476","url":"https://clinicaltrials.gov/study/NCT05546476"}],"tags":["pancreatic-evidence"],"related":["survivorship-roadmap","idea-pdac-enzyme-replacement-prescribing-by-default"],"cancers":["pancreatic","metastatic-pdac"],"sections":["supportive-care","nutrition-lifestyle"],"technologies":[],"targets":[],"drugs":["ponsegromab","folfirinox","gemcitabine-nab-paclitaxel"],"companies":["pfizer"],"institutions":[],"pathways":[],"terms":["performance-status"],"trials":[],"people":[],"bottlenecks":["b-cachexia-supportive","b-aging-comorbidity","b-trial-design"],"keyPapers":["paper-groarke-ponsegromab-cancer-cachexia-nejm-2024","paper-fearon-lancet-oncol","paper-roberts-pert-survival-pancreatic-cancer-pancreatology-2019"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Adding GDF-15 blockade to first-line chemotherapy in pancreatic cancer patients with cachexia or raised GDF-15 increases the relative dose intensity of chemotherapy delivered by 10 percentage points and preserves lean mass, and this translates into longer overall survival.","rationale":"The mechanism is validated in humans, a third of the phase 2 population had pancreatic cancer, and treatment delivery is the variable that links wasting to survival.","test":"Randomised phase 2 or 3 in first-line metastatic or locally advanced disease, stratified by GDF-15 and weight loss, co-primary endpoints relative dose intensity and lean mass by CT at 12 weeks, overall survival key secondary; enzyme replacement and dietetic support protocolised in every arm.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":5},{"id":"idea-tr2-rwe-combination-emulation","kind":"idea","name":"Emulate combination trials from real-world data to triage which ones to run","aka":[],"tldr":"Combinations used off-label in over 200 patients in clinico-genomic databases can be analysed by target trial emulation. Emulations cannot replace trials, but they can rule out the pairs with no signal and flag those with large effects before money is spent on randomised studies.","summary":"Target trial emulation with clinico-genomic databases can estimate effects of combinations that are used in practice but never randomised. Emulations cannot replace trials but can deprioritise pairs with no signal and flag those with large effects. The proposal is a standing programme that emulates every combination used in over 200 patients in the database and publishes ranked results with pre-registered protocols.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Too many combinations to test): Palmer & Sorger, Combination cancer therapy can confer benefit via patient-to-patient variability without drug additivity or synergy (Cell 2017)","url":"https://doi.org/10.1016/j.cell.2017.11.009"}],"tags":[],"related":["tempus","foundation-medicine","genie"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["real-world-evidence"],"trials":[],"people":[],"bottlenecks":["b-combination-space","b-real-world-evidence"],"keyPapers":["paper-palmer-cell"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Combinations flagged as futile in pre-registered emulations will subsequently fail randomised testing in at least 80% of cases, allowing trialists to redirect resources.","rationale":"Target trial emulation reproduced the results of several oncology trials when confounding was addressable; its false negatives are rarer than its false positives, which suits a triage role.","test":"Pre-register emulations for ten combinations with pending randomised readouts and score concordance when trials report.","maturity":"early-clinical","actor":"data","cost":"small","horizonYears":2},{"id":"idea-tr1-target-trial-emulation-to-prioritise-rcts","kind":"idea","name":"Emulate the trial in real-world data first to decide which trials to run","aka":[],"tldr":"Before spending millions on a randomised trial, analyse existing patient records as if the trial had already happened. If the answer is obvious or the question is unanswerable, skip or redesign the trial.","summary":"Funders require a target-trial emulation in linked EHR or registry data as part of any application for a comparative-effectiveness trial: the emulation estimates the likely effect size, event rates, eligible population and recruitment feasibility, and identifies confounders to stratify on. Trials proceed where emulation is inconclusive or where residual confounding is plausible; the emulation also serves as a pre-registered comparator for the trial's result.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Trial design, endpoints and cost): Davis et al., Availability of evidence of benefits on survival and quality of life of cancer drugs approved by EMA 2009-13 (BMJ 2017)","url":"https://doi.org/10.1136/bmj.j4530"}],"tags":[],"related":["genie","seer"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["real-world-evidence"],"trials":[],"people":[],"bottlenecks":["b-trial-design","b-real-world-evidence","b-funding-allocation"],"keyPapers":["paper-davis-bmj"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Trials prioritised by emulation will have a higher rate of informative (positive or clearly negative) results and lower rates of underpowered or unfeasible studies than trials prioritised by expert opinion alone.","rationale":"Target-trial emulation has reproduced randomised results in several therapeutic areas when done carefully; it is cheap relative to a trial and improves design assumptions (event rates, effect sizes) that commonly fail.","test":"A funder runs emulations for all comparative-effectiveness proposals over two funding rounds and follows the completed trials for informativeness versus the previous rounds.","maturity":"early-clinical","actor":"data","cost":"small","horizonYears":2},{"id":"idea-data-full-data-with-abstract","kind":"idea","name":"End the abstract-to-paper gap: require full results with any conference presentation","aka":[],"tldr":"Trial results are often presented at conferences months or years before the full paper appears, leaving doctors to act on slides. Require that the full structured results are published the same day.","summary":"Practice-changing results are frequently presented as late-breaking abstracts with full publication lagging a year or more, and some never appear. The proposal is a joint policy of the major congresses and journals: any presented phase 3 result must be accompanied by simultaneous publication or deposition of the full structured results package (protocol, statistical analysis plan, results tables), with the abstract itself openly licensed.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Knowledge reaches practice too slowly): Morris, Wooding & Grant, The answer is 17 years, what is the question (JRSM 2011)","url":"https://doi.org/10.1258/jrsm.2011.110180"}],"tags":[],"related":["idea-data-structured-trial-results-deposit"],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["asco","esmo"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-knowledge-diffusion","b-negative-results"],"keyPapers":["paper-morris-j-r-soc-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Simultaneous deposition will eliminate the median lag between presentation and full availability and reduce discrepancies between abstracts and eventual papers.","rationale":"Studies find meaningful discrepancies between conference abstracts and subsequent publications; the New England Journal of Medicine and others already coordinate simultaneous publication for some trials, showing feasibility.","test":"Measure abstract-to-publication lag and discrepancy rate for phase 3 oncology trials presented at major congresses over two years; implement the policy at one congress and re-measure.","maturity":"speculative","actor":"policy","cost":"small","horizonYears":2},{"id":"idea-data-ipd-deposit-enforcement","kind":"idea","name":"Enforce individual participant data sharing as a condition of publication and funding","aka":[],"tldr":"Journals and funders already ask trialists to share patient-level data; almost nobody checks. Make it a checked condition with real consequences.","summary":"ICMJE requires data-sharing statements, and funders such as the NIH require sharing plans, but audits find that a minority of oncology trials actually make individual participant data available. The proposal is a joint enforcement mechanism: deposit to an accredited repository (Vivli, YODA, Project Data Sphere) within 18 months of primary publication, verified by the journal before publication of any secondary paper, and by funders before any new award.","asOf":"2026-09-08","links":[{"label":"Vivli","url":"https://vivli.org/"},{"label":"Project Data Sphere","url":"https://www.projectdatasphere.org/"}],"tags":[],"related":["clinicaltrials-gov"],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-data-silos","b-ip-collaboration","b-reproducibility"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Verified enforcement will raise actual availability of oncology trial participant data from under 20 percent to over 70 percent within five years, enabling pooled analyses and external validations that are currently impossible.","rationale":"Compliance with trial registration jumped only when ICMJE made it a condition of publication; sharing needs the same enforced condition rather than a statement.","test":"Two major oncology journals adopt verified deposit for one year; compare actual availability of data from their trials against matched journals without the rule.","maturity":"speculative","actor":"policy","cost":"small","horizonYears":3},{"id":"idea-bio2-engineered-bacteria-payloads","kind":"idea","name":"Engineered bacteria that live in tumours and manufacture drugs there","aka":[],"tldr":"Some harmless bacteria naturally grow in the low-oxygen core of tumours. Engineering them to produce immune-activating drugs turns them into tiny factories inside the tumour.","summary":"Attenuated Salmonella and E. coli Nissle strains colonise hypoxic tumour cores selectively, and synthetic biology allows quorum-controlled payload release of STING agonists, CD47 nanobodies or cytokines. Early human experience with intratumoural bacterial therapy exists, and BCG in bladder cancer is a century-old proof that live bacteria can drive anti-tumour immunity. Safety, biocontainment and manufacturing are the real hurdles.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Cold tumours and the immunosuppressive microenvironment): Haslam & Prasad, Estimation of the percentage of US patients eligible for and responding to checkpoint inhibitors (JAMA Netw Open 2019)","url":"https://doi.org/10.1001/jamanetworkopen.2019.2535"}],"tags":[],"related":[],"cancers":["pancreatic","colorectal"],"sections":[],"technologies":["sting-agonist","bcg-and-intravesical-therapy","cytokine-therapy"],"targets":["cd47"],"drugs":["bcg-intravesical"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-tme-immunosuppression","b-undruggable-targets"],"keyPapers":["paper-haslam-jama-netw-open","paper-cd47-pancreatic-pharmacol-res-2022","paper-cd47-colorectal-cancers-basel-2025","paper-cd47-colorectal-cancer-res-commun-2025"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A quorum-regulated engineered strain colonises human tumours at detectable levels after intravenous or intratumoural dosing and produces measurable local payload and immune activation without bacteraemia above grade 2.","rationale":"Tumour hypoxia is a selectivity handle that no small molecule can match, and payload release can be genetically gated to bacterial density inside the lesion. Escalating dose is a colonisation problem rather than a plasma exposure problem.","test":"First-in-human intratumoural dosing in accessible lesions with quantitative colonisation, payload and safety endpoints, plus a documented kill-switch demonstration.","maturity":"preclinical-evidence","actor":"industry","cost":"medium","horizonYears":9},{"id":"idea-moon-engineered-immune-surveillance","kind":"idea","name":"Engineered immune surveillance: long-lived programmed immune cells that patrol for early cancer","aka":[],"tldr":"For people at very high cancer risk, install a small population of engineered immune cells that live for years and destroy cells showing early cancer signals before a tumour forms.","summary":"Immune surveillance normally eliminates most incipient tumours; carriers of BRCA, Lynch or TP53 mutations and people with clonal haematopoiesis face lifelong high risk. Advances in memory stem T cell engineering, logic-gated receptors responsive to stress ligands or shared neoantigens, and safety switches make a persistent, low-level engineered surveillance population conceivable. The proposal is a research programme to define target ligands of pre-malignant cells, engineer persistent gated cells with off-switches, and demonstrate prevention in genetically engineered mouse models before first-in-human studies in the highest-risk carriers.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Dormant cells and minimal residual disease): Tie et al., ctDNA analysis guiding adjuvant therapy in stage II colon cancer (NEJM 2022)","url":"https://doi.org/10.1056/NEJMoa2200075"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["car-t","tcr-t","car-nk-macrophage","armored-car"],"targets":["tp53","brca"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-dormancy-mrd","b-hereditary-risk","b-tme-immunosuppression"],"keyPapers":["paper-vogelstein-surfing-p53-network-nature-2000"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Engineered surveillance cells reduce tumour incidence by more than half in high-risk mouse models without autoimmunity, and persist for over a year in humans with an acceptable safety profile.","rationale":"Cell therapies persist for years in some patients; logic gating and stress-ligand recognition have preclinical proof; prevention needs far fewer cells than treating bulk disease.","test":"Five-year preclinical programme with a go/no-go on incidence reduction and safety in two mouse models, then a phase 1 in Li-Fraumeni or Lynch carriers with persistence and safety endpoints.","maturity":"speculative","actor":"research","cost":"large","horizonYears":12},{"id":"idea-rejuv-second-cancer-latency-cohort-for-new-drugs","kind":"idea","name":"Enrol every new systemic therapy into a registry linkage that will still report in thirty years","aka":[],"tldr":"A second cancer after radiotherapy can take forty years to appear. Checkpoint inhibitors and antibody-drug conjugates have been in first-line use for a few, so nobody can say anything about their late effects, and nobody is building the thing that could.","summary":"The honest position on the late effects of modern treatment is that they are unmeasurable, not that they are absent. Follow-up of commercial CAR-T cohorts is short relative to the latency of second cancers; the FDA's 2024 labelling action on secondary T-cell malignancy states no incidence; whether the immunotherapies and antibody-drug conjugates now in first-line use carry such a risk is not yet measurable. The same applies in the reassuring direction: whether smaller modern radiotherapy fields lowered the forty-year second cancer rate is not known because nobody has been followed that long.\n\nWaiting will not fix this, because the follow-up mechanism does not exist. Trial follow-up ends when the registration endpoint is met; extension studies are voluntary and lose people; pharmacovigilance describes reporting, not incidence. The paediatric cohorts show what works: abstract exposures at entry, link to registries, and the answer arrives decades later without anyone having to remember.\n\nThe proposal is to make that routine. At the point of approval, every new systemic cancer therapy enters a national registry linkage keyed to the treatment record, with second cancers, cardiovascular events and mortality reported from routine data rather than from sponsor follow-up. The marginal cost is in the linkage and the consent architecture, and it is the same infrastructure a late-effects registry needs, which is why the two proposals belong together.","asOf":"2026-10-02","links":[{"label":"Schaapveld et al., Second cancer risk up to 40 years after treatment for Hodgkin's lymphoma (NEJM 2015)","url":"https://doi.org/10.1056/NEJMoa1505949"}],"tags":["rejuvenation","survivorship","open-problem","second-cancers","latency"],"related":["rejuv-tx-secondary-t-cell-malignancy","rejuv-tx-gene-modified-follow-up","rejuv-second-platinum-and-parp-inhibitors","idea-acc-national-late-effects-registry","idea-moon-adult-late-effects-registry","rejuvenation-roadmap"],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["rejuv-agenda-latency-outruns-the-evidence","rejuv-agenda-late-effects-are-not-counted","b-real-world-evidence","b-data-silos"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A registry linkage established at approval and running on routine data will produce measurable late-effect rates for modern therapies within fifteen to twenty-five years, which no current mechanism will.","rationale":"The latency of solid second cancers after treatment exceeds the follow-up of every modern drug programme. Gene-modified cell therapy already carries a fifteen-year long-term follow-up recommendation, and the transplant facet records its honest limit: no randomised evidence exists, or could exist, that following an individual for fifteen years improves their outcome, and loss to follow-up is the known failure mode. A passive registry linkage does not depend on the individual staying in contact.","test":"Pilot in a country with linked national cancer registry, prescribing and hospital data: enrol one modern drug class at approval, demonstrate that second cancers and cardiovascular events can be reported from routine data at five years, and compare completeness against the sponsor's own extension study.","maturity":"speculative","actor":"regulator","cost":"medium","horizonYears":15},{"id":"idea-moon-dormancy-eradication-programme","kind":"idea","name":"Eradicate dormant cancer cells: a programme to wake and kill or lock asleep disseminated cells","aka":[],"tldr":"Many relapses come from cancer cells that hid dormant for years. Find drugs that either force them awake so chemotherapy kills them, or keep them asleep for life.","summary":"Disseminated tumour cells in bone marrow and other niches survive therapy in a quiescent state maintained by niche signals (TGF-beta 2, BMP, NR2F1, autophagy) and cause late relapse in breast, prostate and melanoma. Preclinical work shows both awakening strategies (sensitising to chemotherapy) and dormancy-enforcing strategies (NR2F1 agonists, 5-azacytidine plus retinoic acid, CDK4/6 inhibitors) can reduce metastasis. The proposal is a coordinated programme: standardised dormant-cell models, biomarkers of dormancy burden in patients (bone marrow and ctDNA), and adjuvant trials of dormancy-directed therapy in patients with detected disseminated cells.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Dormant cells and minimal residual disease): Tie et al., ctDNA analysis guiding adjuvant therapy in stage II colon cancer (NEJM 2022)","url":"https://doi.org/10.1056/NEJMoa2200075"}],"tags":[],"related":[],"cancers":["breast-hr-positive","prostate","melanoma"],"sections":[],"technologies":["cdk46-inhibitor","epigenetic-drugs"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["mrd"],"trials":[],"people":[],"bottlenecks":["b-dormancy-mrd","b-metastasis-biology"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A dormancy-directed adjuvant regimen reduces late relapse (beyond three years) in high-risk hormone-receptor-positive breast cancer by a third compared with standard endocrine therapy.","rationale":"Late relapse is the dominant failure mode in several common cancers and no current therapy targets the dormant state; the biology is now tractable and measurable.","test":"Phase 2 randomised trial in patients with detectable disseminated tumour cells after standard adjuvant therapy, with disseminated cell clearance and distant recurrence as endpoints.","maturity":"preclinical-evidence","actor":"research","cost":"large","horizonYears":10},{"id":"idea-fund-paediatric-deferral-escrow","kind":"idea","name":"Escrow a share of adult revenue until the paediatric study is done","aka":[],"tldr":"Companies often delay the childhood cancer studies they are required to do. A slice of the adult drug's revenue would be held back until the paediatric trial is completed.","summary":"Under the US RACE for Children Act and EU Paediatric Regulation, companies must plan paediatric studies for molecularly relevant cancer drugs, but deferrals and waivers are common and completion lags years. A rule would place a small percentage (for example 2%) of adult sales into escrow from launch, released on completion of the agreed paediatric study or forfeited to a paediatric oncology trials fund after the deadline. This aligns commercial interest with timely paediatric evidence without new appropriations.","asOf":"2026-09-08","links":[{"label":"FDA Oncology Center of Excellence pediatric oncology","url":"https://www.fda.gov/about-fda/oncology-center-excellence/pediatric-oncology"}],"tags":[],"related":["idea-fund-amc-paediatric-rare"],"cancers":["neuroblastoma","all-leukemia","sarcoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["childrens-oncology-group"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-incentive-misalignment","b-rare-cancers"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Revenue escrow reduces the median delay from adult approval to paediatric study completion by at least two years and lifts on-time completion above 75% for drugs approved under the rule.","rationale":"Deferral without financial consequence is why paediatric plans drift; financial holdbacks are standard tools in construction and procurement contracts. The RACE Act closed the loophole of indication-based exemption but left timing weakly enforced.","test":"Implement in one jurisdiction for newly approved oncology drugs with paediatric requirements and compare completion timelines with the prior cohort.","maturity":"speculative","actor":"regulator","cost":"small","horizonYears":4},{"id":"idea-tnbc-uk-ethnicity-stratified-outcome-reporting","kind":"idea","name":"Ethnicity-stratified outcome reporting for triple-negative breast cancer in NHS cancer statistics","aka":[],"tldr":"The one UK study to look found young Black women had more triple-negative breast cancer and worse survival than White women despite equal chemotherapy, but it ended in 2008 and covered women under 41. Routine cancer statistics could report triple-negative incidence, stage and survival by ethnicity every year; at present they do not.","summary":"The UK and NHS page for triple-negative breast cancer records that no UK registry publishes triple-negative incidence or survival by ethnicity; this idea holds the evidence that exists. The POSH cohort (2,915 women aged 40 or under, recruited 2000 to 2008) found triple-negative disease in 26.1 percent of Black against 18.6 percent of White women, larger tumours at presentation, and five-year overall survival of 71.1 versus 82.4 percent with chemotherapy use equal at about 89 percent; Black ethnicity was an independent risk factor for distant relapse. United States registries have reported triple-negative incidence by ethnicity since 2010. English cancer registration records receptor status and ethnicity but does not publish triple-negative outcomes by ethnicity, so whether the POSH gap persists in the immunotherapy era, whether it extends to older women, and whether it reflects stage at diagnosis, germline variants, subtype or treatment delivery is unknown.","asOf":"2026-09-24","links":[{"label":"Copson et al.: POSH, ethnicity and outcome (Br J Cancer 2014)","url":"https://europepmc.org/article/MED/24149174"}],"tags":["tnbc-evidence"],"related":["idea-tnbc-disparities-in-access-and-outcomes"],"cancers":["tnbc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["cruk"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-diversity","b-data-silos","b-care-fragmentation"],"keyPapers":["paper-copson-posh-ethnicity-young-breast-cancer-uk-bjc-2014","paper-howlader-us-incidence-breast-subtypes-jnci-2014","paper-scott-tnbc-disparities-uscs-cancer-2019"],"journals":[],"dependsOn":[],"notes":["The UK and NHS page for triple-negative breast cancer records the data gaps this reporting would close: the NDRS registration statistics answered 403 on 24 September 2026, the Scottish open data carry no receptor field, and the Welsh and Northern Irish tables are by site and stage only."],"hypothesis":"Annual publication of triple-negative breast cancer incidence, stage at diagnosis, treatment received and three-year survival by ethnic group from national cancer registration will show a persisting survival gap for Black women in England of at least 5 percentage points and will identify stage at diagnosis and time to treatment as modifiable contributors.","rationale":"A disparity that is measured can be acted on; the data fields exist and the analysis is routine for other cancers and other countries.","test":"A one-off linked analysis of the 2015 to 2022 diagnostic cohort with receptor status, ethnicity, stage, treatment and survival, followed by inclusion of a triple-negative-by-ethnicity table in the annual cancer survival statistics, with a companion germline and subtype sub-study in a consented cohort.","maturity":"speculative","actor":"data","cost":"small","horizonYears":3},{"id":"idea-nl-alcohol-minimum-pricing-cancer-endpoints","kind":"idea","name":"Evaluate alcohol minimum unit pricing against cancer incidence","aka":[],"tldr":"Scotland and Wales put a floor under the price of alcohol. Deaths from liver disease have already fallen. Cancer takes longer to show, so someone has to keep measuring for a decade.","summary":"Minimum unit pricing (Scotland 2018, Wales 2020, Ireland 2022) reduced alcohol sales by about 3% and alcohol-specific deaths by about 13% within three years. Alcohol-attributable cancers (oral, oesophageal, liver, colorectal, breast) have latencies of 10-20 years, so the cancer benefit, which is a large part of the policy's justification, will only be visible if a pre-registered evaluation with cancer registry linkage is funded for the long term. Natural-experiment designs comparing Scotland with England, and dose-response by deprivation, are feasible because registries are complete.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Prevention we already have is not deployed): Islami et al., Proportion of cancer attributable to modifiable risk factors (CA 2018)","url":"https://doi.org/10.3322/caac.21440"}],"tags":[],"related":["idea-prev-alcohol-cancer-warning-labels","idea-prev-smokefree-generation-evaluation"],"cancers":["head-and-neck","esophageal","hcc","colorectal","breast-hr-positive"],"sections":["nutrition-lifestyle","prevention"],"technologies":["alcohol-reduction-labelling"],"targets":[],"drugs":[],"companies":[],"institutions":["iarc","cruk"],"pathways":[],"terms":["alcohol-attributable-cancer"],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption","b-real-world-evidence"],"keyPapers":["paper-islami-ca-cancer-j-clin"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Within 10-15 years of introduction, minimum unit pricing reduces incidence of alcohol-attributable cancers by 3-5% relative to England, with the largest reductions in the most deprived quintile, and the effect is dose-dependent on price level.","rationale":"Cancer is the largest alcohol-attributable cause of death in the long run, but policy evaluations stop at 3-5 years. A pre-registered, decade-long registry analysis protects against both premature declarations of success and industry claims of failure.","test":"Pre-registered interrupted time-series and synthetic-control analysis using national cancer registries for Scotland, Wales, Ireland and comparators, stratified by deprivation and sex, with annual reporting; funded by public health agencies for 15 years.","maturity":"being-tested-at-scale","actor":"policy","cost":"small","horizonYears":10},{"id":"idea-prev-clean-air-never-smoker-endpoints","kind":"idea","name":"Evaluate clean-air policies using lung cancer in never-smokers","aka":[],"tldr":"Air pollution causes lung cancer in people who never smoked. Clean air zones and coal phase-outs should be tracked against never-smoker lung cancer rates.","summary":"Fine particulate pollution promotes EGFR-mutant lung cancer in never-smokers (Francis Crick Institute work). Propose linked-data evaluation of air-quality interventions (London ULEZ, Chinese coal-to-gas conversion) with never-smoker, EGFR-mutant lung cancer incidence as endpoints, and pre-registered modelling.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Prevention we already have is not deployed): Islami et al., Proportion of cancer attributable to modifiable risk factors (CA 2018)","url":"https://doi.org/10.3322/caac.21440"}],"tags":[],"related":["lung-cancer-evidence-roadmap","idea-lung-never-smoker-disease-its-own-programme"],"cancers":["nsclc"],"sections":["prevention"],"technologies":[],"targets":["egfr"],"drugs":[],"companies":[],"institutions":["francis-crick"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption"],"keyPapers":["paper-islami-ca-cancer-j-clin"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A sustained 10 micrograms per cubic metre PM2.5 reduction reduces never-smoker lung cancer incidence by at least 10% within 15 years.","rationale":"Mechanistic and epidemiological evidence exists, and the policies are being enacted anyway, so evaluation is cheap.","test":"Registry-linked natural experiments with molecular subtyping.","maturity":"speculative","actor":"data","cost":"small","horizonYears":10},{"id":"idea-tr1-evening-weekend-trial-clinics","kind":"idea","name":"Evening and weekend trial clinics for working-age patients","aka":[],"tldr":"Trial visits happen on weekdays during working hours, which excludes people with jobs or caring duties, so trials under-enrol patients under 65. Running research clinics in the evening and at weekends, cluster-randomised across one network for a year, is a cheap test of whether that matters.","summary":"Trial visits happen on weekdays during working hours, which excludes people with jobs or caring duties, so research units such as The Christie and The Royal Marsden would offer at least one evening and one weekend session a week for trial visits, infusions and sampling, with protocol windows written to permit it and staff costs covered by the trial budget. Sites with extended hours are expected to enrol more patients under 65 and in employment and to miss fewer visits. The test cluster-randomises research units in one network to extended hours for a year and compares enrolment demographics and visit adherence. Speculative and cheap, it addresses the bottlenecks Trials enrol too few, too slowly and Trials do not represent the people who get cancer.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Trials enrol too few, too slowly): Unger et al., Systematic review of barriers to cancer trial participation (JNCI 2019)","url":"https://doi.org/10.1093/jnci/djy221"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["the-christie","royal-marsden"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-enrolment","b-trial-diversity"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Sites with extended-hours research clinics will enrol a higher share of patients under 65 and in employment, and will have fewer missed visits.","rationale":"Extended hours increased uptake in cancer screening and in chronic disease clinics; trial participation shares the same time cost structure.","test":"Cluster-randomise research units in one network to extended hours for a year; compare enrolment demographics and visit adherence.","maturity":"speculative","actor":"clinic","cost":"small","horizonYears":1},{"id":"idea-data-ai-audit-trail-in-ehr","kind":"idea","name":"Every AI output logged in the record with input hash, version and clinician response","aka":[],"tldr":"Whenever an AI tool gives a result about a patient, the hospital system would permanently record what it saw, which version it was, what it said and what the doctor did with it.","summary":"Most AI outputs are transient and not stored, making retrospective audit, harm investigation and performance measurement impossible. The proposal is a standard for AI audit trails in the EHR (FHIR resources capturing model identifier and version, input references and hashes, output, confidence, timestamp, and the clinician's acceptance or override), required for all deployed cancer AI and feeding post-market performance reporting.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (AI that is built but not validated or deployed): Wu et al., How medical AI devices are evaluated: limitations and recommendations from an analysis of FDA approvals (Nature Medicine 2021)","url":"https://doi.org/10.1038/s41591-021-01312-x"}],"tags":[],"related":["idea-data-ai-post-market-performance-reporting"],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-ai-validation","b-data-silos"],"keyPapers":["paper-wu-nat-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Universal audit trails will make post-market performance measurable at near-zero marginal cost and will allow root-cause analysis of AI-related harms that are currently unexplainable.","rationale":"Aviation's flight recorders and pharmacy's dispensing logs made safety investigation and improvement possible; AI in care has no equivalent record.","test":"Implement the audit trail standard at five sites; demonstrate quarterly performance reports derived from it; test its use in retrospective review of ten discordant cases.","maturity":"early-clinical","actor":"engineering","cost":"small","horizonYears":1},{"id":"idea-tr2-combo-readiness-dossier","kind":"idea","name":"Every approved cancer drug ships with a public combination-readiness data pack","aka":[],"tldr":"Require that approved cancer drugs come with a standard set of data (blood levels, drug interactions, toxicity profile) so anyone can design a safe combination trial without asking the company.","summary":"Combination trial designers need pharmacokinetic profiles, metabolic pathways, QT effects, myelosuppression kinetics and immunogenicity data that sit in confidential regulatory dossiers. A standardised, machine-readable 'combination-readiness' annex published at approval would let academics and other companies design combination studies and predict overlapping toxicity without bilateral negotiation.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Too many combinations to test): Palmer & Sorger, Combination cancer therapy can confer benefit via patient-to-patient variability without drug additivity or synergy (Cell 2017)","url":"https://doi.org/10.1016/j.cell.2017.11.009"}],"tags":[],"related":["fda-approvals","drugbank-chembl","idea-tr2-combination-template-agreement"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-combination-space","b-ip-collaboration"],"keyPapers":["paper-palmer-cell"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Publication of readiness packs increases the number of investigator-initiated combination trials involving newly approved drugs by at least 30% within three years.","rationale":"Open pharmacology data (as in the FDA labels' clinical pharmacology sections, but structured and complete) removes an information asymmetry that currently forces every combination through the originator.","test":"Pilot voluntary packs for ten recently approved oncology drugs and count investigator-initiated combination trials registered within two years compared with matched drugs without packs.","maturity":"speculative","actor":"regulator","cost":"small","horizonYears":3},{"id":"idea-tr2-phd-replication-year","kind":"idea","name":"Every cancer biology PhD begins with a funded replication of a published finding","aka":[],"tldr":"Make the first project of every cancer biology doctoral student a funded, pre-registered attempt to repeat a published finding chosen from a curated list of translationally relevant results, with the outcome published in a replication registry. Students learn power analysis, blinding and reporting, and the field gets thousands of replications a year.","summary":"First-year doctoral students need training projects with clear methods and a defined endpoint; replications provide exactly that, while teaching pre-registration, power analysis, blinding and reporting. Programmes that have tried this (in psychology) report strong educational outcomes. A cancer biology version, with findings chosen from a curated list of translationally important results and outcomes published in a replication registry, would create a steady replication workforce at marginal cost.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Preclinical results do not reproduce): Errington et al., Investigating the replicability of preclinical cancer biology (eLife 2021)","url":"https://doi.org/10.7554/eLife.71601"}],"tags":[],"related":["idea-tr2-replication-set-aside","idea-tr2-replication-status-badge"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-reproducibility","b-workforce"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Participating programmes will publish at least one replication per student, and students will show measurably better methodological practice in subsequent thesis work than matched controls.","rationale":"Training and replication are complementary: the student gains skills, the field gains evidence, and the incentive problem is sidestepped because the student is not competing for novelty.","test":"Pilot in five doctoral programmes for three cohorts; track replications published and assess later methodological quality.","maturity":"speculative","actor":"research","cost":"medium","horizonYears":4},{"id":"idea-tr2-reference-compound-panels","kind":"idea","name":"Every drug screen includes standard reference compounds whose performance is published","aka":[],"tldr":"Drug sensitivity results for the same cell line and drug differ substantially between large screens. Every published cancer drug screen should include a defined panel of reference compounds with published expected activity ranges per reference cell line, reported in a standard format, so results from different labs can be calibrated against each other.","summary":"Drug sensitivity results for the same cell line and drug differ substantially between large screens (the CCLE versus GDSC discordance). A defined panel of reference compounds (with expected potency ranges per reference cell line) included in every published screen, and reported in a standard format, would allow cross-study calibration and reveal systematic differences in assay conditions.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Preclinical results do not reproduce): Errington et al., Investigating the replicability of preclinical cancer biology (eLife 2021)","url":"https://doi.org/10.7554/eLife.71601"}],"tags":[],"related":["depmap","idea-tr2-cell-line-passport"],"cancers":[],"sections":[],"technologies":["functional-drug-testing","crispr-screens"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-reproducibility","b-preclinical-models"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Including reference panels will let discordant screens be reconciled by calibration, reducing cross-study potency disagreement by at least half for the drugs and lines covered.","rationale":"Clinical laboratories use internal standards in every run; preclinical pharmacology mostly does not, and the resulting variance has been quantified.","test":"Define the panel; run it in five laboratories under their standard conditions; test whether calibration reconciles their results on a shared set of new compounds.","maturity":"speculative","actor":"research","cost":"small","horizonYears":2},{"id":"idea-prev-opt-out-cessation-in-lung-screening","kind":"idea","name":"Every lung screening visit includes stop-smoking medicine, opt-out","aka":[],"tldr":"Lung screening is a teachable moment. Giving cessation medicine and support by default at every scan, unless the person opts out, roughly doubles quit rates.","summary":"Lung screening is a teachable moment, so this idea makes opt-out cessation pharmacotherapy, varenicline or cytisine, plus counselling a programme standard at every low-dose CT visit, with quit rate as a headline performance indicator. Opt-out cessation in screening programmes such as the YESS trial improves quit rates, cessation delivers more life-years than the scan itself in modelling, and the population is captive. The aim is to roughly double biochemically verified quit rates among screened smokers at one year. The test is a programme-level comparison plus an RCT of opt-out versus opt-in delivery. Being tested at scale, it addresses the bottleneck Prevention we already have is not deployed and links to smoking cessation in cancer patients.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Prevention we already have is not deployed): Islami et al., Proportion of cancer attributable to modifiable risk factors (CA 2018)","url":"https://doi.org/10.3322/caac.21440"}],"tags":[],"related":[],"cancers":["nsclc"],"sections":["prevention","early-detection"],"technologies":["ct"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption"],"keyPapers":["paper-islami-ca-cancer-j-clin"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Opt-out embedded cessation increases 12-month biochemically verified quit rates among screened smokers from about 10% to at least 20%.","rationale":"Cessation delivers more life-years than the scan itself in modelling, and the population is captive.","test":"Programme-level comparison plus an RCT of opt-out versus opt-in delivery.","maturity":"being-tested-at-scale","actor":"clinic","cost":"small","horizonYears":2},{"id":"idea-moon-results-in-plain-words","kind":"idea","name":"Every pathology and genomic report ships with a signed plain-language version","aka":[],"tldr":"When your biopsy or gene test comes back, you get a version written for you, drafted by software and checked and signed by your clinician, alongside the technical report.","summary":"Patients now receive laboratory results in portals before their clinician has spoken to them, often in dense pathology language. The proposal is that laboratories and hospitals generate a plain-language companion for every diagnostic report (what was tested, what was found, what it usually means, what happens next) using a language model constrained to templates and the actual report text, released only after clinician sign-off. Templates should be co-written with patient groups and cover the twenty most common report types first.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Patients lack understanding, navigation and agency): Basch et al., Overall survival results of a trial assessing patient-reported outcomes for symptom monitoring during routine cancer treatment (JAMA 2017)","url":"https://doi.org/10.1001/jama.2017.7156"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["cgp","histopathology-ihc"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["vus","ngs"],"trials":[],"people":[],"bottlenecks":["b-patient-voice","b-knowledge-diffusion"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Plain companions reduce patient anxiety and misinterpretation after portal release and cut clarifying calls and messages by a third, without introducing clinically significant errors after sign-off.","rationale":"Pathology and molecular reports follow structured formats amenable to templated translation; clinician sign-off keeps accountability where it belongs, and the workload is small relative to the messages the reports currently generate.","test":"Pilot in two centres across pathology and next-generation sequencing reports: measure error rate on blinded expert review, patient comprehension, anxiety scores and message volume against matched controls.","maturity":"early-clinical","actor":"engineering","cost":"small","horizonYears":2},{"id":"idea-tr1-opt-out-research-contact-register","kind":"idea","name":"Every patient is asked once at diagnosis whether researchers may contact them","aka":[],"tldr":"At diagnosis, people would be asked a single question: may we contact you about research that fits your cancer? Those who say yes would be findable by trial teams without repeated cold approaches.","summary":"A health-system-level consent-to-contact register, recorded in the EHR at diagnosis, allowing approved trial teams to approach registered patients whose records match a protocol. The UK's Be Part of Research and Scotland's SHARE register are precedents; the idea is to make the question a mandatory element of cancer diagnosis pathways and to link the register to matching tools.","asOf":"2026-09-08","links":[{"label":"NIHR Be Part of Research","url":"https://bepartofresearch.nihr.ac.uk/"},{"label":"SHARE (Scottish Health Research Register)","url":"https://www.registerforshare.org/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["cruk"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-enrolment"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Health systems with a diagnosis-time consent-to-contact register will approach eligible patients more often and enrol more, particularly in trials for rare or biomarker-defined cancers where prospective identification matters most.","rationale":"Most patients say they would join a trial if asked; the bottleneck is being asked. A register moves identification from chance encounters to systematic search.","test":"Compare trial approach and enrolment rates between regions with and without a mandatory register, adjusting for trial availability.","maturity":"being-tested-at-scale","actor":"policy","cost":"small","horizonYears":2},{"id":"idea-data-accelerated-approval-registry-condition","kind":"idea","name":"Every patient on an accelerated-approval drug enrolled in a registry until confirmation","aka":[],"tldr":"Accelerated approvals rest on surrogate endpoints, and confirmatory trials take years and are sometimes never completed. Making registry enrolment with automatic outcome capture a condition of prescribing under accelerated approval would give regulators a real-world signal on benefit and toxicity within about two years, while the confirmatory trial runs.","summary":"Accelerated approvals rest on surrogate endpoints; confirmatory trials take a median of several years and some are never completed. The proposal makes registry enrolment with automatic outcome capture (via mCODE and registry linkage) a condition of prescribing under accelerated approval, giving regulators an interim real-world signal on survival and toxicity while the confirmatory trial runs. The FDA's 2023 authority to require confirmatory trials be underway at approval is the policy hook; the registry is the complementary data hook.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Weak real-world evidence and registries): Gyawali, Hey & Kesselheim, Assessment of the clinical benefit of cancer drugs receiving accelerated approval (JAMA Intern Med 2019)","url":"https://doi.org/10.1001/jamainternmed.2019.0462"}],"tags":[],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["accelerated-approval","real-world-evidence","os"],"trials":[],"people":[],"bottlenecks":["b-real-world-evidence","b-regulatory-fragmentation"],"keyPapers":["paper-gyawali-jama-intern-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Mandatory registries will detect lack of overall survival benefit for accelerated-approval indications that later fail confirmation at least 18 months earlier than the confirmatory trial does.","rationale":"Several accelerated-approval oncology indications were withdrawn only after years of use; real-world survival on those drugs was knowable much earlier had the data been collected.","test":"Retrospectively emulate the registry for five withdrawn indications using existing real-world data and estimate when a survival signal would have been detectable; prospectively apply to the next ten accelerated approvals.","maturity":"speculative","actor":"regulator","cost":"medium","horizonYears":3},{"id":"idea-tr1-universal-routine-cost-coverage","kind":"idea","name":"Every payer covers routine care costs for trial participants, in every country","aka":[],"tldr":"Outside US Medicare and Medicaid, joining a trial can leave the patient or hospital paying for the ordinary care that goes with it, and billing uncertainty blocks participation in middle-income countries. Requiring every insurer and public system to cover routine care costs removes a hidden barrier.","summary":"Legislation or payer policy guaranteeing coverage of routine patient care costs during trial participation, as US Medicare has since 2000 and Medicaid since the CLINICAL TREATMENT Act (effective 2022), extended to all private insurers, to national health systems that lack explicit rules, and to public insurers in middle-income countries where trial participation can be blocked by billing uncertainty.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Trials enrol too few, too slowly): Unger et al., Systematic review of barriers to cancer trial participation (JNCI 2019)","url":"https://doi.org/10.1093/jnci/djy221"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["asco","nci"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-enrolment","b-global-access"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Jurisdictions adopting explicit routine-cost coverage will see an increase in trial enrolment among publicly insured and lower-income patients within two years.","rationale":"Coverage uncertainty is a documented reason sites do not offer trials to certain patients and hospitals decline to host them. Removing it is cheap for payers because routine care would be paid for anyway.","test":"Compare Medicaid-insured trial enrolment before and after the CLINICAL TREATMENT Act across states with and without prior coverage mandates; replicate in a middle-income country adopting the rule.","maturity":"being-tested-at-scale","actor":"payer","cost":"medium","horizonYears":3},{"id":"idea-reg-public-assessment-reports-all","kind":"idea","name":"Every regulator publishes its full assessment report so others can rely on it","aka":[],"tldr":"Europe already publishes a detailed report explaining why each drug was approved. If every country did, smaller regulators could reuse the work.","summary":"EMA's European Public Assessment Reports and FDA's review packages are public; most other regulators publish little. Reliance pathways depend on access to assessment reports, which are currently exchanged bilaterally under confidentiality agreements, if at all. The proposal is an ICH-level commitment that every member publishes a structured assessment report within 60 days of decision, with a standard redaction protocol for commercially confidential information, and deposits it in a shared index.","asOf":"2026-09-08","links":[{"label":"EMA medicines and EPARs","url":"https://www.ema.europa.eu/en/medicines"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-regulatory-fragmentation","b-knowledge-diffusion"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Countries with access to indexed assessment reports register new oncology medicines faster and with fewer requests for additional data than countries without, and the number of formal reliance decisions rises year on year.","rationale":"Reliance cannot scale on bilateral trust; it needs a public evidence base. Publication also exposes divergence, which itself drives convergence.","test":"Build the shared index with the reports already public (EMA, FDA, Health Canada, TGA, Swissmedic) and track its use by LMIC regulators; then negotiate publication commitments from PMDA, NMPA, ANVISA and CDSCO.","maturity":"early-clinical","actor":"regulator","cost":"small","horizonYears":2},{"id":"idea-bio1-reverse-translation-resistance-models","kind":"idea","name":"Every resistance mechanism found in a patient must be rebuilt in the laboratory","aka":[],"tldr":"When doctors discover how a tumour escaped a drug, that finding usually stops at a paper. Recreating it in a model gives everyone a system to test the next drug against.","summary":"Clinically observed resistance mechanisms (mutations, bypass activation, lineage switch) are frequently reported but rarely converted into a distributed, isogenic model. A standing reverse-translation facility would engineer each reported mechanism into relevant backgrounds, verify the resistance phenotype, and distribute the lines openly, creating a growing panel that drug developers must test new candidates against.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Lab models that fail to predict what happens in patients): Wong, Siah & Lo, Estimation of clinical trial success rates (Biostatistics 2019)","url":"https://doi.org/10.1093/biostatistics/kxx069"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["crispr-screens","functional-drug-testing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["resistance"],"trials":[],"people":[],"bottlenecks":["b-preclinical-models","b-resistance"],"keyPapers":["paper-wong-biostatistics"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A public panel of clinically derived resistance models identifies cross-resistance for a substantial fraction of next-generation agents before they enter trials, and correctly anticipates their clinical failure settings.","rationale":"Next-generation inhibitors are often developed against laboratory-derived resistance that does not match what patients actually develop; a clinically anchored panel aligns discovery with reality.","test":"Build 50 clinically derived resistance models for three drug classes, profile ten clinical-stage successor agents against them blinded, and compare with subsequent trial results.","maturity":"speculative","actor":"research","cost":"medium","horizonYears":5},{"id":"idea-prev-opportunistic-ct-ai-registry","kind":"idea","name":"Every routine CT scan checked by AI for early cancer signs, with a tracked follow-up pathway","aka":[],"tldr":"Hundreds of millions of CT scans are done each year for other reasons. Software could check each one for early lung, kidney, liver and pancreas changes, but only if a follow-up system exists.","summary":"Opportunistic screening algorithms exist for lung nodules, renal masses, liver lesions, and body composition. Propose a module running on all adult CTs with structured incidental-finding output, an automated tracking system to ensure follow-up, and a registry recording downstream procedures and cancers found so harm can be measured.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The hardest cancers are found late): Crosby et al., Early detection of cancer (Science 2022)","url":"https://doi.org/10.1126/science.aay9040"}],"tags":[],"related":[],"cancers":["nsclc","rcc","hcc","pancreatic"],"sections":["early-detection","imaging"],"technologies":["ct","radiology-ai-screening"],"targets":[],"drugs":[],"companies":["aidoc"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-early-detection","b-overdiagnosis"],"keyPapers":["paper-crosby-science"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Opportunistic AI on routine CT detects one to two additional stage I-II cancers per 1,000 scans, with follow-up completion of at least 90% when tracking is automated, versus under 50% today for incidental findings.","rationale":"Incidental findings are already common but get lost in free-text reports; the failure is tracking, not detection.","test":"Prospective pilot in two hospital systems (100,000 scans), measuring incremental cancers, stage, procedures per cancer, and lost-to-follow-up rate.","maturity":"early-clinical","actor":"engineering","cost":"medium","horizonYears":3},{"id":"idea-prev-annual-overdiagnosis-reporting","kind":"idea","name":"Every screening programme must publish its overdiagnosis rate each year","aka":[],"tldr":"Screening finds cancers that would never have caused harm, but programmes only report cancers found. Publishing the estimated overdiagnosis rate alongside would make the trade-off visible.","summary":"Overdiagnosis is estimable from excess cumulative incidence versus unscreened comparators and from modelling. Propose a regulatory requirement for annual reporting of estimated overdiagnosis, false positives, and procedures per cancer, in standard formats, for every publicly funded screening programme and any reimbursed MCED.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Overdiagnosis and false alarms): Welch & Black, Overdiagnosis in cancer (JNCI 2010)","url":"https://doi.org/10.1093/jnci/djq099"}],"tags":[],"related":[],"cancers":[],"sections":["early-detection"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["ppv"],"trials":[],"people":[],"bottlenecks":["b-overdiagnosis","b-incentive-misalignment"],"keyPapers":["paper-welch-j-natl-cancer-inst"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Mandatory reporting drives programme changes (thresholds, intervals) that reduce overdiagnosis by at least 20% within five years without reducing advanced-cancer detection.","rationale":"Current metrics reward detection volume; what is measured is managed.","test":"Adopt in one country; compare programme changes with non-adopters.","maturity":"speculative","actor":"regulator","cost":"small","horizonYears":3},{"id":"idea-data-structured-genomic-reports","kind":"idea","name":"Every tumour genomic report machine-readable and deposited nationally","aka":[],"tldr":"Genetic test results for tumours are mostly PDFs. Require labs to also send a computer-readable version to a national store, so variants can be linked to what treatments worked.","summary":"NGS reports from commercial and hospital labs are delivered as PDFs; the structured variant calls rarely enter the record. The HL7 Genomics Reporting implementation guide and mCODE genomics profiles define the format. The proposal requires, as a condition of payer coverage for tumour sequencing, that laboratories deposit structured variant, TMB, MSI and fusion data to a national variant-outcome store linked to registry outcomes, building on AACR Project GENIE and Genomics England.","asOf":"2026-09-08","links":[{"label":"HL7 Genomics Reporting IG","url":"https://hl7.org/fhir/uv/genomics-reporting/"},{"label":"AACR Project GENIE","url":"https://www.aacr.org/professionals/research/aacr-project-genie/"}],"tags":[],"related":["genie","cbioportal","civic","oncokb"],"cancers":[],"sections":["ai-computation"],"technologies":["ngs","cgp"],"targets":[],"drugs":[],"companies":["foundation-medicine","tempus","caris","guardant-health"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-data-silos","b-real-world-evidence","b-rare-cancers"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A payer-mandated structured deposit will link genomics to outcomes for more than 80 percent of sequenced patients within three years, allowing variant-level outcome queries (for example rare KRAS alleles) that currently require bespoke consortia.","rationale":"GENIE showed that pooled genomic-clinical data across 19 centres yields answers on rare variants no single centre can; a mandate extends this from volunteer academic centres to all sequenced patients.","test":"Pilot with one national payer and the three largest commercial labs: measure the proportion of covered tests deposited in structured form and time to first published variant-outcome analysis.","maturity":"early-clinical","actor":"payer","cost":"medium","horizonYears":3},{"id":"idea-tr1-ngs-report-live-trial-match","kind":"idea","name":"Every tumour sequencing report lists open, nearby, matched trials pulled live","aka":[],"tldr":"The report that tells a patient their tumour's mutations should also tell them which trials are recruiting for those mutations within reach, with the status checked that week rather than copied from a stale list.","summary":"Genomic testing laboratories would embed a matching step at report generation: variants are mapped to trial arms (OncoKB and CIViC annotations, ClinicalTrials.gov structured eligibility), filtered by geography and current recruiting status confirmed by direct query, and listed with a contact. Some commercial reports do this partly; the idea makes live status confirmation and geography the standard, with the same section in public-lab reports.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Trials enrol too few, too slowly): Unger et al., Systematic review of barriers to cancer trial participation (JNCI 2019)","url":"https://doi.org/10.1093/jnci/djy221"}],"tags":[],"related":["oncokb","civic","clinicaltrials-gov"],"cancers":[],"sections":[],"technologies":["cgp","ai-trial-matching","companion-diagnostic"],"targets":[],"drugs":[],"companies":["foundation-medicine","tempus","caris","guardant-health"],"institutions":[],"pathways":[],"terms":["ngs"],"trials":[],"people":[],"bottlenecks":["b-trial-enrolment","b-knowledge-diffusion"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Reports with live, local, matched trial listings increase genomically matched trial enrolment by at least 50 percent relative to reports listing only 'potential trials' without status or geography, as measured in a lab's own follow-up data.","rationale":"The genomic report is one of the few documents both the oncologist and patient read carefully; trial listings there are seen at the right moment. Stale status is the main reason clinicians ignore existing listings.","test":"A large testing laboratory randomises report templates (live matched listing vs standard) across ordering practices for six months and follows enrolment through its registry.","maturity":"early-clinical","actor":"industry","cost":"small","horizonYears":1},{"id":"idea-moon-integrative-oncology-bridge","kind":"idea","name":"Evidence-based integrative oncology in every cancer centre to meet demand safely","aka":[],"tldr":"Offer the complementary approaches that have evidence (acupuncture for nausea and pain, exercise, mindfulness, yoga) inside the cancer centre, so patients do not seek them, and worse, elsewhere.","summary":"Demand for complementary approaches is high and unmet demand pushes patients toward unregulated providers. ASCO and the Society for Integrative Oncology have issued joint guidelines identifying interventions with supporting evidence for pain, anxiety, fatigue and nausea. The proposal is that cancer centres provide these services under clinical governance, staffed by trained practitioners, with clear statements of what is and is not evidenced, and that payers cover the evidenced components.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Misinformation and unproven therapies): Johnson et al., Cancer misinformation and harmful information on Facebook and other social media (JNCI 2022)","url":"https://doi.org/10.1093/jnci/djab141"}],"tags":[],"related":["mindfulness-based-interventions"],"cancers":[],"sections":[],"technologies":["exercise-oncology"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-misinformation","b-toxicity-qol"],"keyPapers":["paper-johnson-j-natl-cancer-inst"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Centres offering integrative services report lower use of unproven external therapies, higher disclosure of complementary use, and improved symptom scores compared with matched centres.","rationale":"Meeting a real need inside the system keeps patients within evidence-based care and builds trust for the conversations about what does not work.","test":"Matched comparison of centres with and without integrative programmes on external unproven therapy use, disclosure and symptom PROs; embedded randomised trials of specific components.","maturity":"being-tested-at-scale","actor":"clinic","cost":"medium","horizonYears":3},{"id":"idea-tr1-adaptive-therapy-randomised-phase-2","kind":"idea","name":"Evolution-guided 'adaptive therapy' dosing tested in randomised phase 2 trials","aka":[],"tldr":"Adaptive therapy uses just enough drug to keep a tumour in check, pausing when the burden falls and resuming when it rises, so drug-sensitive cells suppress resistant ones. A prostate cancer pilot with abiraterone lengthened time to progression against historical controls on half the drug; randomised phase 2 trials are the next step.","summary":"Adaptive therapy modulates dosing on tumour burden (PSA, imaging or ctDNA), pausing when burden falls below a threshold and resuming when it rises, to maintain a population of sensitive cells that compete with resistant clones. A pilot in metastatic castration-resistant prostate cancer using abiraterone showed prolonged time to progression versus historical controls with roughly half the cumulative drug. The proposal is randomised phase 2 trials in prostate, melanoma and ovarian cancer with pre-specified adaptive algorithms.","asOf":"2026-09-08","links":[{"label":"Integrating evolutionary dynamics into treatment of metastatic castrate-resistant prostate cancer (Nature Communications 2017)","url":"https://www.nature.com/articles/s41467-017-01968-5"}],"tags":[],"related":["prostate-roadmap","idea-prostate-bipolar-androgen-therapy-phase-3-on-pfs2"],"cancers":["prostate","melanoma","ovarian"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["moffitt"],"pathways":[],"terms":["resistance"],"trials":[],"people":[],"bottlenecks":["b-dose-optimisation","b-resistance"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Adaptive dosing will extend time to progression by at least 30 percent relative to continuous dosing in at least one of three settings tested, with lower cumulative drug exposure.","rationale":"Evolutionary game theory and mathematical models of competition between sensitive and resistant clones predict that maximum-dose therapy selects fastest for resistance; the pilot data are consistent with the model.","test":"Three randomised phase 2 trials (n about 100 each) of adaptive versus continuous dosing with time to progression as the primary endpoint and cumulative dose and QoL as secondaries.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":4},{"id":"idea-bio1-evolutionary-tumour-boards","kind":"idea","name":"Evolutionary tumour boards with a modeller in the room","aka":[],"tldr":"Cancer is an evolving population, but treatment decisions are rarely made with an evolutionary biologist present. Add one to the weekly meeting and see whether decisions change.","summary":"Molecular tumour boards translate mutations into drugs; none formally consider clonal structure, evolvability, or the expected resistance trajectory. Moffitt has piloted an evolutionary tumour board. The proposal is to fund such boards at ten centres with a common case template (clone structure, growth kinetics, predicted escape routes, proposed schedule) and to audit whether recommendations and outcomes differ from standard boards.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Tumour heterogeneity and clonal evolution): Gerlinger et al., Intratumor heterogeneity and branched evolution (NEJM 2012)","url":"https://doi.org/10.1056/NEJMoa1113205"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["moffitt"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-tumor-heterogeneity","b-workforce"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Evolutionary tumour board review changes the recommended sequence or schedule in at least a quarter of advanced-cancer cases and is associated with longer time to second progression in the cases where the recommendation is followed.","rationale":"Every other field that manages evolving populations, from infectious disease to pest control, uses explicit evolutionary reasoning; oncology has the data (serial ctDNA, imaging) but not the forum.","test":"Prospective parallel review of 300 cases by standard and evolutionary boards; measure recommendation concordance, and follow outcomes where the evolutionary recommendation was adopted.","maturity":"speculative","actor":"clinic","cost":"small","horizonYears":2},{"id":"idea-cost-gold-card-oncology","kind":"idea","name":"Exempt oncologists who follow the pathway from prior authorisation","aka":[],"tldr":"If a practice's requests are approved almost every time, asking again wastes everyone's money; gold-card rules give such practices automatic approval and audit them instead.","summary":"Medicare Advantage insurers made nearly 53 million prior authorisation determinations in 2024 and overturned 80.7% of the denials that were appealed (KFF). Texas passed the first gold-card law in 2021: clinicians with approval rates above 90% are exempt from prior authorisation for those services. Oncology is well suited because on-pathway prescribing (NCCN categories 1 and 2A) is easy to audit retrospectively. Several insurers have announced gold-card programmes; making the rule statutory and pathway-based would extend it.","asOf":"2026-09-10","links":[{"label":"KFF: Medicare Advantage insurers made nearly 53 million prior authorization determinations in 2024","url":"https://www.kff.org/medicare/medicare-advantage-insurers-made-nearly-53-million-prior-authorization-determinations-in-2024/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["nccn-org","asco"],"pathways":[],"terms":["nccn-compendium"],"trials":[],"people":[],"bottlenecks":["b-care-fragmentation","b-incentive-misalignment","b-workforce"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Gold-carding oncology practices with over 90% approval rates will cut prior authorisation volume by more than half with no increase in off-pathway prescribing on audit.","rationale":"Overturn rates above 80% mean most denials are wrong; the review adds delay and cost without changing the treatment.","test":"Compare gold-carded and non-gold-carded practices on time to treatment start, administrative hours, drug spend and pathway concordance.","maturity":"being-tested-at-scale","actor":"payer","cost":"small","horizonYears":1},{"id":"idea-data-rapid-guideline-translation","kind":"idea","name":"Expert-verified translation of guideline updates into 20 languages within 30 days","aka":[],"tldr":"Most oncology guidelines exist only in English, and national adaptations lag by years and often diverge. Machine translation checked by a clinician-verifier per language could publish each recommendation update in 20 languages within 30 days, side by side with the source and with local adaptations flagged explicitly.","summary":"Most oncology guidelines exist only in English; national adaptations lag by years and often diverge. With computable guidelines and machine translation quality now high for medical text, a service could translate each recommendation update into 20 languages with a clinician-verifier per language, publishing side by side with the source and flagging local adaptations explicitly.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Knowledge reaches practice too slowly): Morris, Wooding & Grant, The answer is 17 years, what is the question (JRSM 2011)","url":"https://doi.org/10.1258/jrsm.2011.110180"}],"tags":[],"related":["idea-data-computable-living-guidelines"],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-knowledge-diffusion","b-global-access"],"keyPapers":["paper-morris-j-r-soc-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Rapid translation will reduce the lag between English guideline updates and their availability in other languages from years to under 30 days and increase guideline-concordant care in non-English-speaking regions.","rationale":"Language is a documented barrier to guideline uptake; the cost of translation was the obstacle and has collapsed.","test":"Translate one guideline's updates for one year into ten languages; measure time to availability, verifier correction rates, and access by clinicians in target countries.","maturity":"speculative","actor":"engineering","cost":"small","horizonYears":1},{"id":"idea-tr1-exposure-response-before-dose-selection","kind":"idea","name":"Exposure-response modelling with a pre-set target exposure before any dose is chosen","aka":[],"tldr":"Instead of picking the dose by how much patients can tolerate, measure drug levels in blood and relate them to both benefit and harm across patients, then choose the dose that hits the sweet spot.","summary":"Registrational packages include population PK and exposure-response analyses for efficacy and the main toxicities, with the target exposure range declared before phase 3 and the chosen dose justified against it; sparse PK sampling in all trial participants makes this feasible. Regulators publish the exposure-response basis for the label dose.","asOf":"2026-09-08","links":[{"label":"FDA Oncology Center of Excellence: Project Optimus","url":"https://www.fda.gov/about-fda/oncology-center-excellence/project-optimus"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["pharmacokinetics","pivotal-trial","regulatory-agencies"],"trials":[],"people":[],"bottlenecks":["b-dose-optimisation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Programmes with pre-specified exposure-response dose selection will select doses below MTD more often and will require fewer post-marketing dose changes than programmes without.","rationale":"Exposure-response is standard in most therapeutic areas; oncology has lagged because of the MTD tradition. Many approved oncology drugs have label doses on the flat part of the efficacy curve and the steep part of the toxicity curve.","test":"Audit new oncology approvals for the presence and use of exposure-response analysis in dose justification and compare subsequent dose-related label changes.","maturity":"being-tested-at-scale","actor":"regulator","cost":"small","horizonYears":2},{"id":"idea-cost-inflation-rebates-commercial","kind":"idea","name":"Extend Medicare's inflation rebates to employer plans","aka":[],"tldr":"Since 2023 manufacturers must rebate Medicare when a drug's price rises faster than inflation; applying the same rule to commercial plans would end the yearly list-price rises that drive coinsurance up.","summary":"The Inflation Reduction Act of 2022 requires manufacturers to pay rebates on Part B and Part D drugs whose prices rise faster than the consumer price index. Commercial plans have no such protection, and oncology drugs have historically had annual list-price increases well above inflation. Extending the rebate to the commercial market, or letting employers piggyback on the Medicare calculation, would cap post-launch price growth across the whole system.","asOf":"2026-09-10","links":[{"label":"CMS: Medicare Prescription Drug Inflation Rebate Program","url":"https://www.cms.gov/inflation-reduction-act-and-medicare/inflation-rebates-medicare"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["drug-price-transparency","financial-toxicity"],"trials":[],"people":[],"bottlenecks":["b-drug-pricing"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Commercial inflation rebates will hold post-launch list-price growth for oncology drugs to the rate of general inflation within two years of enactment, with launch prices rising less than the rebate saves.","rationale":"The Medicare rebate has already reduced price increases for affected drugs according to CMS; the commercial market is where most working-age patients with cancer are insured.","test":"Compare list-price trajectories of oncology drugs before and after the Medicare rebate took effect, then model and pilot the commercial extension in a state with an all-payer claims database.","maturity":"speculative","actor":"policy","cost":"medium","horizonYears":3},{"id":"idea-bio1-p53-mutant-reactivator-expansion","kind":"idea","name":"Extend p53 reactivation beyond the Y220C mutation","aka":[],"tldr":"One faulty version of the p53 guardian protein can now be repaired by a drug that plugs a hole in it. Systematically hunting for similar holes in other faulty versions could help far more patients.","summary":"Rezatapopt (PC14586) binds a crevice created by the TP53 Y220C mutation and restores wild-type folding, with responses reported in early trials. Y220C is only around 1 percent of TP53 mutations. A systematic structural and covalent-fragment campaign across the ten commonest TP53 hotspots (R175H, R248Q, R273H, R282W and others), using cryo-EM, deep mutational scanning and AI structure prediction of mutant conformational ensembles, could find analogous pockets or cysteine-reactive sites.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The undruggable drivers): Dang et al., Drugging the 'undruggable' cancer targets (Nature Reviews Cancer 2017)","url":"https://doi.org/10.1038/nrc.2017.36"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["ai-drug-design"],"targets":["tp53"],"drugs":[],"companies":[],"institutions":[],"pathways":["p53-cell-cycle"],"terms":[],"trials":[],"people":[],"bottlenecks":["b-undruggable-targets"],"keyPapers":["paper-vogelstein-surfing-p53-network-nature-2000","paper-dang-nat-rev-cancer"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"At least two additional TP53 hotspot mutants have a reproducible small-molecule-stabilisable conformation that restores p53 transcriptional activity in cells by more than 50 percent of wild-type.","rationale":"TP53 is mutated in about half of all cancers; a mutation-specific reactivator strategy is now clinically validated in principle, and the chemistry (covalent stabilisers, chaperone-like binders) is transferable.","test":"A three-year structure-first campaign with a public compound and structure release; cell-based p53 reporter and transcriptomic restoration assays as the go/no-go for each hotspot.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":6},{"id":"idea-tr1-extended-interval-checkpoint-dosing","kind":"idea","name":"Extended-interval immunotherapy: give checkpoint inhibitors every 8-12 weeks once stable","aka":[],"tldr":"Immunotherapy antibodies stay active in the body for weeks, yet are often given every two or three weeks. After a few months, spacing doses out to every two or three months might work as well, with fewer hospital visits and much lower cost.","summary":"Non-inferiority trials randomising patients with response or stable disease after 3-6 months of PD-1/PD-L1 blockade to extended-interval dosing (e.g., every 8-12 weeks, PK-guided) versus standard intervals, with PFS or TTF non-inferiority and cumulative dose, cost and toxicity as secondaries. Receptor occupancy studies show saturation at exposures far below label; PK-guided interval extension has been piloted.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Wrong doses): FDA Oncology Center of Excellence, Project Optimus","url":"https://www.fda.gov/about-fda/oncology-center-excellence/project-optimus"}],"tags":[],"related":[],"cancers":["nsclc","melanoma"],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":["pd1","pdl1"],"drugs":["pembrolizumab","nivolumab","atezolizumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["checkmate-227","checkmate-915","fianlimab-phase3-melanoma","keynote-042","relativity-098"],"people":[],"bottlenecks":["b-dose-optimisation","b-drug-pricing","b-toxicity-qol"],"keyPapers":["paper-topalian-anti-pd1-nejm-2012","paper-keynote-024-nejm-2016","paper-keynote-010-lancet-2016"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Extended-interval dosing in responders will be non-inferior for PFS with at least 50 percent lower cumulative drug exposure and fewer immune-related adverse events requiring intervention.","rationale":"PD-1 receptor occupancy on circulating T cells is saturated at low concentrations and persists for months; the half-life of these antibodies is around three weeks, and dosing intervals were set for trial convenience and revenue rather than pharmacology.","test":"A cooperative-group non-inferiority trial in NSCLC and melanoma responders, powered for a pre-agreed PFS margin, with PK sampling to support a label change.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":4},{"id":"idea-tcr-t-beyond-hla-a2","kind":"idea","name":"Extending sarcoma TCR-T beyond HLA-A*02","aka":[],"tldr":"Today's engineered T-cell therapies for sarcoma only work in the ~40-50% of people with one particular HLA type; new receptors for other HLA types would open them to everyone.","summary":"Afamitresgene autoleucel and letetresgene autoleucel, the engineered T-cell receptor therapies for synovial sarcoma, work only in people whose HLA type is A*02:01, A*02:05 or A*02:06, which excludes around half of patients. This idea would open TCR-T to everyone by discovering receptors that recognise the same antigens, MAGE-A4 and NY-ESO-1, presented by other alleles such as HLA-A*24, HLA-B*35 and HLA-C*07. The rationale is that antigen expression is independent of HLA type, so the barrier is a receptor discovery problem, and platforms at Immatics, T-knife and Adaptimmune have already isolated candidate receptors. The proposed test is a basket phase 1/2 across HLA types; the evidence is preclinical, and the idea addresses the bottleneck of rare and paediatric cancers without markets.","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT03967223: IGNYTE-ESO","url":"https://clinicaltrials.gov/study/NCT03967223"}],"tags":[],"related":[],"cancers":["sarcoma"],"sections":[],"technologies":["tcr-t"],"targets":["mage-a4"],"drugs":["afamitresgene-autoleucel","letetresgene-autoleucel"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-spearhead-1-lancet-2024"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"MAGE-A4- or NY-ESO-1-directed TCR-T restricted to HLA-A*24:02 or HLA-B*35 achieves response rates comparable to afami-cel in synovial sarcoma.","rationale":"Antigen expression is HLA-independent; the binding problem is solved by receptor discovery, not biology.","test":"Basket phase 1/2 across HLA types with shared antigen; pooled ORR endpoint.","maturity":"preclinical-evidence"},{"id":"idea-data-multisite-validation-precondition","kind":"idea","name":"External validation at five or more sites in two countries before clearance","aka":[],"tldr":"No cancer AI would be approved until it has been tested on patients from at least five different hospitals in at least two countries, none of which contributed training data.","summary":"Cleared AI devices have frequently been validated on data from one or two sites, often overlapping with development sites. The proposal sets a minimum external validation requirement (at least five independent sites, at least two countries or health systems, no training-site overlap, pre-registered analysis, subgroup reporting) for regulatory clearance of cancer AI, with the sequestered benchmarks as one accepted route.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (AI that is built but not validated or deployed): Wu et al., How medical AI devices are evaluated: limitations and recommendations from an analysis of FDA approvals (Nature Medicine 2021)","url":"https://doi.org/10.1038/s41591-021-01312-x"}],"tags":[],"related":["idea-data-sequestered-prospective-benchmarks"],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-ai-validation","b-regulatory-fragmentation"],"keyPapers":["paper-wu-nat-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Models meeting the requirement will show smaller performance drops on deployment than models cleared under current rules, and the requirement will not materially slow clearance for well-built models.","rationale":"Generalisation failure across sites is the best-documented failure mode of medical AI; multi-site external validation is the direct test and is inexpensive relative to the harm of deploying brittle models.","test":"Compare post-deployment performance drop for cleared models grouped by number of external validation sites; if the association holds, adopt the requirement and re-measure.","maturity":"speculative","actor":"regulator","cost":"small","horizonYears":2},{"id":"idea-fund-duration-trial-exclusivity","kind":"idea","name":"Extra exclusivity for sponsors who run treatment-duration and de-escalation trials","aka":[],"tldr":"Companies lose money when they prove a shorter course works, so they never test it. Give them a modest reward, such as extra months of exclusivity, when they do.","summary":"Regulators grant a defined exclusivity extension (for example six months, as for paediatric studies) to sponsors who complete an adequately powered randomised trial of treatment duration, stopping rules or dose de-escalation for an approved oncology drug within a set period after approval, regardless of the result. Alternatively, such trials become a condition of full approval after accelerated approval. Most immunotherapy is given for two years or until progression with no evidence for either; a legislated carrot that outweighs revenue loss from shorter courses could fix the incentive at low public cost.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Incentives reward me-too drugs and marginal gains): Upadhaya et al., PD1/PDL1 inhibitor clinical trial landscape (Nat Rev Drug Discov 2022)","url":"https://doi.org/10.1038/d41573-022-00030-4"}],"tags":[],"related":["idea-fund-payer-funded-pragmatic-trials","idea-fund-value-based-patent-extension"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":["nivolumab","pembrolizumab","osimertinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-incentive-misalignment","b-dose-optimisation","b-toxicity-qol"],"keyPapers":["paper-upadhaya-nat-rev-drug-discov"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A duration-trial exclusivity incentive results in at least half of newly approved immune checkpoint and targeted therapies having a completed randomised duration or de-escalation trial within five years of approval, compared with a small minority today.","rationale":"Paediatric exclusivity created hundreds of paediatric studies that would otherwise not have happened, demonstrating industry response to modest exclusivity rewards. Duration trials such as CheckMate 153 (one year versus continuous nivolumab) and DANTE show the questions are answerable and matter to patients.","test":"Model revenue effects and legislate a pilot in one jurisdiction; count duration and de-escalation trials initiated by sponsors for drugs approved under the pilot versus before.","maturity":"speculative","actor":"regulator","cost":"small","horizonYears":5},{"id":"idea-tr1-factorial-dose-finding-for-combinations","kind":"idea","name":"Factorial dose finding for drug combinations instead of full dose of everything","aka":[],"tldr":"When two cancer drugs are combined, each is usually given at its full single-agent dose, which often proves too toxic. Testing a grid of dose pairs would find combinations that work with tolerable side effects.","summary":"Combination phase 1/2 studies use model-based two-agent dose-finding (partial-order CRM, BOIN-COMB) or factorial randomised designs to explore dose pairs, with efficacy and tolerability read-outs at each pair, rather than fixing one agent at its label dose and escalating the other. Regulators expect a justification for each agent's dose in combination labels.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Wrong doses): FDA Oncology Center of Excellence, Project Optimus","url":"https://www.fda.gov/about-fda/oncology-center-excellence/project-optimus"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["checkpoint-inhibitor","kinase-inhibitors"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-dose-optimisation","b-combination-space"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Combination programmes using two-dimensional dose finding will select regimens with lower total dose intensity and substantially lower discontinuation than full-dose combinations, with equal or better efficacy.","rationale":"Many combination failures (and several withdrawals) were driven by intolerability at full doses of each component; synergy, where present, implies that less of each is needed.","test":"Apply two-dimensional dose finding to three new combination programmes and compare discontinuation and efficacy in subsequent trials with combinations developed conventionally.","maturity":"speculative","actor":"industry","cost":"medium","horizonYears":3},{"id":"idea-tr2-factorial-adjuvant-generics","kind":"idea","name":"Factorial trials that test several cheap generics at once in the adjuvant setting","aka":[],"tldr":"One large trial can test aspirin, a statin, metformin and exercise at the same time by randomising each separately, answering four questions for the price of one.","summary":"A 2x2x2 factorial randomises each patient to each intervention independently, so main effects of several low-cost interventions are tested with the same participants. The Add-Aspirin trial and the earlier ATAC-style factorials show feasibility. Generic repurposing candidates have no sponsor, so factorial efficiency is the only way many will ever be tested.","asOf":"2026-09-08","links":[{"label":"Add-Aspirin trial","url":"https://www.addaspirintrial.org/"}],"tags":[],"related":["cruk","idea-tr2-perpetual-platforms"],"cancers":["colorectal"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-combination-space","b-generic-repurposing"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A factorial adjuvant trial of three generics in colorectal cancer will report main effects for all three with adequate power at a per-question cost below one third of separate trials.","rationale":"Interventions with different mechanisms rarely interact strongly; factorial designs exploit this. Cooperative groups have the infrastructure.","test":"Design and fund a 2x2x2 factorial in stage III colon cancer (for example aspirin, a statin and vitamin D) with disease-free survival as the primary endpoint.","maturity":"early-clinical","actor":"research","cost":"large","horizonYears":7},{"id":"idea-prev-family-history-auto-match","kind":"idea","name":"Family history collected by app and matched to testing criteria automatically","aka":[],"tldr":"Doctors rarely take a full family history, so eligibility for genetic testing goes undetected. An app that gathers the history from the patient, feeds it into the record and checks it against NCCN or NICE criteria would identify several-fold more eligible people and, the proposal estimates, roughly double the number tested.","summary":"Doctors rarely take a full family history, so this idea integrates patient-entered family history into the EHR at every new-patient visit, auto-matches it to NCCN or NICE testing criteria and triggers automatic referral or mainstream testing. Tools such as MeTree and CanRisk exist but are not part of routine care, and eligibility is common but rarely detected. The aim is several-fold more guideline-eligible individuals identified and roughly twice as many tested. The test is a cluster RCT in primary care networks. At early-clinical maturity it addresses the bottleneck Inherited risk is mostly unidentified and links to germline testing.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Inherited risk is mostly unidentified): Childers et al., National estimates of genetic testing in women with breast or ovarian cancer (JCO 2017)","url":"https://doi.org/10.1200/JCO.2017.73.6314"}],"tags":[],"related":[],"cancers":[],"sections":["prevention"],"technologies":["germline-testing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-hereditary-risk"],"keyPapers":["paper-childers-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Automated capture increases identification of guideline-eligible individuals at least three-fold and testing at least two-fold.","rationale":"Eligibility is common (about 5-10% of adults) but rarely detected.","test":"Run a cluster RCT in primary care networks.","maturity":"early-clinical","actor":"engineering","cost":"small","horizonYears":2},{"id":"idea-prev-hpylori-family-test-and-treat","kind":"idea","name":"Family-based H. pylori test-and-treat to prevent stomach cancer","aka":[],"tldr":"Stomach cancer is largely caused by a bacterium that spreads in households. Testing and treating whole families, not individuals, would stop reinfection and prevent cancer.","summary":"Mass eradication in Linqu County and the Matsu Islands reduced gastric cancer incidence, and the Chinese family-based consensus recommends household testing. Propose family-unit test-and-treat with stool antigen testing and tailored therapy, evaluated in a cluster-randomised design in high-incidence regions.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Prevention we already have is not deployed): Islami et al., Proportion of cancer attributable to modifiable risk factors (CA 2018)","url":"https://doi.org/10.3322/caac.21440"}],"tags":[],"related":[],"cancers":["gastric"],"sections":["prevention"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["cams-cancer-hospital"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption"],"keyPapers":["paper-islami-ca-cancer-j-clin"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Family-based eradication reduces reinfection to under 2% per year and gastric cancer incidence by at least 30% over 15 years versus individual-based treatment.","rationale":"Household transmission drives reinfection; eradication reduces cancer most in those without established pre-malignant lesions.","test":"Cluster RCT in 50,000 households with ten-year incidence follow-up.","maturity":"being-tested-at-scale","actor":"policy","cost":"large","horizonYears":10},{"id":"idea-fap-theranostics-pancancer","kind":"idea","name":"FAP theranostics as a pan-cancer stromal strategy","aka":[],"tldr":"Instead of finding a different target for each cancer, hit the scaffolding cells that almost all solid tumours share.","summary":"Rather than finding a different target for each cancer, this idea hits the cancer-associated fibroblasts that almost all solid tumours share. FAP-targeted alpha or beta radioligands such as FAP-2286 would be given to FAPI-PET-avid pancreatic, gastric and sarcoma patients irrespective of tumour-cell genotype, delivering radiation to the stroma with crossfire into adjacent tumour cells and depleting the fibroblasts that exclude T cells. Stroma is genetically stable, so resistance mutations are not expected. The test is phase 2 FAP-2286 cohorts selected by FAPI PET, with paired biopsies and a PD-1 combination in pancreatic cancer. At early-clinical maturity it addresses the bottleneck Cold tumours and the immunosuppressive microenvironment.","asOf":"2026-09-04","links":[{"label":"Kratochwil et al., 68Ga-FAPI PET/CT: tracer uptake in 28 different kinds of cancer (Journal of Nuclear Medicine 2019)","url":"https://doi.org/10.2967/jnumed.119.227967"}],"tags":[],"related":[],"cancers":["pancreatic","gastric","sarcoma"],"sections":[],"technologies":["fapi-pet","radioligand-therapy","targeted-alpha-therapy"],"targets":["fap"],"drugs":["fap-2286"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct07219238"],"people":[],"bottlenecks":[],"keyPapers":["paper-kratochwil-j-nucl-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"FAP-targeted alpha or beta radioligands produce disease control in FAPI-PET-avid pancreatic, gastric, and sarcoma patients irrespective of tumour-cell genotype, and sensitise to immunotherapy by depleting immunosuppressive fibroblasts.","rationale":"Stroma is genetically stable (no resistance mutations); crossfire range of 177Lu (2 mm) covers adjacent tumour cells; CAF depletion relieves T-cell exclusion.","test":"Phase 2 FAP-2286 cohorts with FAPI PET selection and paired biopsies for CAF depletion and T-cell infiltration; combination with PD-1 in pancreatic cancer.","maturity":"early-clinical"},{"id":"idea-mced-plus-fapi","kind":"idea","name":"FAPI PET as the workup for MCED positives","aka":[],"tldr":"When a blood test says 'cancer signal, origin unclear', a FAPI PET scan may find it where FDG cannot.","summary":"When a blood test reports a cancer signal of unclear origin, this idea sends the patient for FAPI PET/CT rather than FDG PET as the first-line work-up. Many MCED-positive patients have no cancer found on standard imaging, which creates anxiety and cost, whereas FAPI PET is more sensitive than FDG in pancreatic, gastric, low-grade and peritoneal disease, exactly the cancers MCED promises to catch, and has low background in liver, brain and bowel. The test is a prospective diagnostic study nested in a Galleri deployment such as the NHS or a PATHFINDER-like cohort, randomising FDG versus FAPI PET. Speculative in maturity, it addresses the bottleneck The hardest cancers are found late and is linked from the ideas on a 28-day MCED-positive resolution pathway and whole-population interception.","asOf":"2026-09-04","links":[{"label":"PATHFINDER: the first prospective test of a multi-cancer blood test in people without symptoms (The Lancet 2023)","url":"https://doi.org/10.1016/S0140-6736(23)01700-2"}],"tags":[],"related":[],"cancers":["pancreatic","gastric","ovarian"],"sections":[],"technologies":["mced","fapi-pet","fdg-pet"],"targets":["fap"],"drugs":["galleri"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"FAPI PET/CT increases the cancer detection rate and reduces time to diagnosis in MCED-positive, FDG-negative or tissue-of-origin-uncertain patients.","rationale":"Complementary biology (stroma vs glucose); FAPI has low background in liver, brain, and bowel.","test":"Prospective diagnostic study nested in a Galleri deployment (e.g., NHS or PATHFINDER-like) randomising FDG vs FAPI PET as first-line workup.","maturity":"speculative"},{"id":"idea-acc-fast-track-relicensing-oncologists","kind":"idea","name":"Fast-track relicensing for refugee, migrant and returning oncology professionals","aka":[],"tldr":"Trained cancer doctors and nurses who have fled conflict or moved countries often spend years unable to practise. A short, competency-based route back to work would add capacity quickly.","summary":"Regulatory barriers keep three groups of qualified oncology professionals out of practice: displaced physicians from conflict zones, migrant specialists awaiting equivalence exams, and parents returning after career breaks. A competency-based, supervised fast track (assessment, a period of supervised practice, and conditional registration) could return them to service within months. Several countries introduced emergency versions during COVID-19 and could make them permanent.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Not enough oncologists, nurses, pathologists, physicists): Yang et al., Projected supply of and demand for oncologists and radiation oncologists through 2025 (JOP 2014)","url":"https://doi.org/10.1200/JOP.2013.001319"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-workforce"],"keyPapers":["paper-yang-j-oncol-pract"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A fast-track scheme will return at least 70% of eligible applicants to supervised oncology practice within six months, with performance on standard quality indicators equal to locally trained peers at one year.","rationale":"Pandemic-era emergency registration showed that supervised conditional practice is safe; the cost of leaving trained specialists idle is high in a shortage.","test":"Implement in two jurisdictions and audit time to practice, retention, and quality indicators against conventional-route registrants.","maturity":"speculative","actor":"regulator","cost":"small","horizonYears":1},{"id":"idea-cost-federal-oral-parity","kind":"idea","name":"Federal oral chemotherapy parity for self-funded employer plans","aka":[],"tldr":"Most states require insurers to charge no more for a cancer pill than for an infusion, but the law does not reach the self-funded employer plans that cover most working Americans; a federal rule would close the gap.","summary":"Oral anticancer drugs are usually covered under the pharmacy benefit with coinsurance on a specialty tier, while infused drugs fall under the medical benefit with a copay. Forty-three states and the District of Columbia have parity laws, but the federal ERISA statute exempts self-funded employer plans, which cover roughly two-thirds of workers with employer coverage. The Cancer Drug Parity Act has been introduced in successive Congresses to apply parity to all plans.","asOf":"2026-09-10","links":[{"label":"Congress.gov: Cancer Drug Parity Act, H.R. 1730 (118th Congress)","url":"https://www.congress.gov/bill/118th-congress/house-bill/1730"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["financial-toxicity"],"trials":[],"people":[],"bottlenecks":["b-drug-pricing","b-regulatory-fragmentation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Federal parity will reduce the share of oral oncology prescriptions abandoned at the pharmacy for cost reasons among self-funded plan members by more than a third, at a premium cost of well under 1%.","rationale":"State parity laws had small premium effects and reduced high out-of-pocket bills; the excluded population is the largest remaining group.","test":"Enactment followed by claims-based evaluation of abandonment rates and out-of-pocket costs in self-funded plans against state-regulated plans.","maturity":"early-clinical","actor":"policy","cost":"small","horizonYears":2},{"id":"idea-data-federated-learning-imaging","kind":"idea","name":"Federated training of pathology and radiology models across hospitals","aka":[],"tldr":"Train one AI on pathology slides and radiology scans from dozens of hospitals without any hospital sharing its images: the model travels to the data. Federated learning has worked for glioblastoma segmentation across 70-plus sites, yet almost every clinical model is still trained at one or two institutions, so a persistent shared training infrastructure is proposed.","summary":"Federated learning has been demonstrated in oncology (for example the multi-national glioblastoma segmentation federation of over 70 sites, and breast-density and pathology consortia), but almost every clinical model is still trained on one or two institutions. The proposal is a persistent federated training infrastructure with secure aggregation, differential privacy options, per-site audit logs and a shared model registry, offered as a public utility to cancer centres.","asOf":"2026-09-08","links":[{"label":"Federated learning for glioblastoma (Pati et al. 2022)","url":"https://www.nature.com/articles/s41467-022-33407-5"}],"tags":[],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":["digital-pathology-ai","pathology-foundation-model","radiology-ai-screening"],"targets":[],"drugs":[],"companies":["owkin"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-data-silos","b-ai-validation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Models trained federatedly across 20 or more sites will generalise to unseen hospitals with less than half the performance drop of single-site models, measured on a sequestered multi-site test set.","rationale":"The largest published federated study (Pati et al., Nature Communications 2022) improved out-of-sample glioblastoma segmentation by a third versus a public-data model. Generalisation failure is the main reason cancer AI does not survive deployment.","test":"Train a pathology model for a standard task (for example mitotic count or HER2 scoring) both centrally on one large site and federatedly across 10 sites; evaluate both on five held-out hospitals in other countries.","maturity":"early-clinical","actor":"engineering","cost":"medium","horizonYears":3},{"id":"idea-moon-fertility-preservation-default","kind":"idea","name":"Fertility preservation offered and funded by default before gonadotoxic treatment","aka":[],"tldr":"Everyone of reproductive age about to have treatment that can cause infertility is offered egg, sperm or tissue freezing, paid for, before treatment starts.","summary":"Guidelines recommend fertility counselling for all patients of reproductive age, but referral rates remain low and cost is a common barrier. The proposal is an opt-out pathway: automatic referral triggered by age and regimen in the prescribing system, guaranteed appointments within a week, and funding from the payer for preservation and storage. Outcomes include referral rate, preservation uptake and treatment delay.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Toxicity and quality of life are undervalued): Di Maio et al., Symptomatic toxicities experienced during anticancer treatment: agreement between patient and physician reporting (JCO 2015)","url":"https://doi.org/10.1200/JCO.2014.57.9334"}],"tags":[],"related":[],"cancers":["hodgkin-lymphoma","all-leukemia","tnbc"],"sections":["rejuvenation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol","b-survivorship"],"keyPapers":["paper-di-maio-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Opt-out referral raises documented fertility counselling above 90% and preservation uptake severalfold without delaying treatment start by more than a few days.","rationale":"Infertility is among the most regretted long-term effects and the intervention window is short; default pathways fix omission better than education.","test":"Stepped implementation across a network; primary endpoint documented counselling and preservation rates, secondary treatment delay and long-term regret.","maturity":"being-tested-at-scale","actor":"payer","cost":"medium","horizonYears":2},{"id":"idea-bio1-tumour-restricted-e3-atlas","kind":"idea","name":"Find E3 ligases that only tumours have, and build degraders around them","aka":[],"tldr":"Protein-destroying drugs work by hijacking cellular waste-disposal machines. Using a machine that is mostly present in cancer cells would make these drugs safer.","summary":"Almost all clinical degraders use cereblon or VHL, both broadly expressed, which limits therapeutic index. Human cells have roughly 600 E3 ligases, many with restricted expression; some are highly enriched in tumour or lineage-specific tissue. The proposal is to map ligase expression across normal and tumour tissue atlases, prioritise tumour-enriched ligases, and develop handles for them, thereby making degraders tissue-selective.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The undruggable drivers): Dang et al., Drugging the 'undruggable' cancer targets (Nature Reviews Cancer 2017)","url":"https://doi.org/10.1038/nrc.2017.36"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["protac-degrader","proteomics"],"targets":[],"drugs":[],"companies":["nurix","kymera"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-undruggable-targets","b-toxicity-qol"],"keyPapers":["paper-dang-nat-rev-cancer"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"At least five E3 ligases show tumour-to-normal expression ratios large enough that a degrader built on them achieves target degradation in tumour tissue with less than a fifth of the degradation in critical normal tissue.","rationale":"Selectivity is the main constraint on degrading essential proteins. Cell-type-restricted ligases such as those in liver, prostate and haematopoietic lineage offer a natural targeting mechanism, analogous to how tissue-restricted antigens enable ADCs.","test":"Bioinformatic prioritisation from GTEx and tumour proteomics, then chemical handle discovery for the top three, with a proof-of-concept degrader of a common target compared against a cereblon-based equivalent for normal-tissue sparing.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":6},{"id":"idea-crc-early-onset-cause-hunt","kind":"idea","name":"Find out what is driving early-onset bowel cancer, starting with colibactin, before extending screening any further","aka":[],"tldr":"Bowel cancer in people under 50 is rising by 2 to 8 percent a year on both sides of the Atlantic and nobody knows why. The strongest lead is a toxin made by some gut bacteria whose damage signature is three times more common in young patients and is stamped on the colon early in life. If that is the cause, the fix is in childhood, not in a screening programme.","summary":"Siegel's age-period-cohort analysis of 490,305 United States cases showed that someone born around 1990 has double the colon cancer risk and quadruple the rectal cancer risk of someone born around 1950; Vuik found the same cohort pattern across 20 European countries, with incidence rising 7.9 percent a year in 20 to 29-year-olds. Neither study can say what changed. Diet, obesity, antibiotic exposure and the microbiome have all been proposed, and Hur's cohort found that each daily sugar-sweetened drink in adolescence carried a relative risk of 1.32, on 109 cases.\n\nThe 2025 genome study is the first mechanistic lead with a plausible timing. Across 981 colorectal cancer genomes from 11 countries, the colibactin signatures SBS88 and ID18 were 3.3 times more common in cancers diagnosed before 40 than after 70, were higher in countries with higher incidence, were imprinted early during tumour development and accounted for about 25 percent of APC driver indels in colibactin-positive cases. Colibactin is made by pks-positive Escherichia coli, which colonise in childhood, which would explain a birth-cohort effect that a screening programme cannot touch.","asOf":"2026-09-24","links":[{"label":"Díaz-Gay et al.: geographic and age variations in mutational processes (Nature 2025)","url":"https://europepmc.org/article/MED/40267983"},{"label":"Siegel et al.: colorectal cancer incidence patterns 1974-2013 (JNCI 2017)","url":"https://europepmc.org/article/MED/28376186"},{"label":"Vuik et al.: rising incidence in young adults in Europe (Gut 2019)","url":"https://europepmc.org/article/MED/31097539"}],"tags":["colorectal-evidence"],"related":["colorectal-roadmap","prevention-roadmap","iarc"],"cancers":["colorectal","early-onset-colorectal"],"sections":["prevention","early-detection"],"technologies":["wes-wgs","colorectal-screening"],"targets":["apc"],"drugs":[],"companies":[],"institutions":[],"pathways":["microbiome-tumour"],"terms":["gut-microbiome-diversity"],"trials":[],"people":[],"bottlenecks":["b-early-detection","b-prevention-adoption","b-translational-valley"],"keyPapers":["paper-diaz-gay-colibactin-geographic-age-mutational-processes-nature-2025","paper-siegel-colorectal-incidence-birth-cohort-jnci-2017","paper-vuik-early-onset-colorectal-europe-gut-2019","paper-hur-sugar-sweetened-beverages-early-onset-colorectal-gut-2021"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A measurable childhood exposure, of which colibactin-producing pks+ Escherichia coli colonisation is the leading candidate, accounts for a substantial share of the birth-cohort rise in early-onset colorectal cancer, and its mutational signature can be detected in normal colonic crypts decades before a tumour appears.","rationale":"The colibactin signature is enriched in the young, geographically patterned in line with incidence, written early in tumour development and directly implicated in APC driver formation. No other proposed exposure has a mechanism that acts at the right age, and no screening policy can prevent cancers whose driver mutations were written before adolescence.","test":"A prospective cohort with stored childhood stool and normal colonic biopsies linked to registry outcomes, plus signature analysis of normal crypts across age bands in an existing biobank; in parallel, a randomised trial of a pks+ Escherichia coli decolonisation or displacement strategy in carriers, with the SBS88 and ID18 crypt burden as the surrogate endpoint. Reject the hypothesis if crypt signature burden does not track birth cohort in the same direction as incidence.","maturity":"preclinical-evidence","actor":"research","cost":"large","horizonYears":8},{"id":"idea-rejuv-thymic-regeneration-in-adults","kind":"idea","name":"Find out whether an adult thymus can be made to work again, with an endpoint a clinician would act on","aka":[],"tldr":"Several agents have been tried for thymic recovery after transplant and none is in routine use. The blocker is as much the missing endpoint as the missing drug.","summary":"After a transplant or intensive therapy, cell counts recover and the range of things the immune system can recognise does not. That deficit is why revaccination programmes exist, why prophylaxis runs for months or years, and why a normal count can reassure falsely. Nothing in routine use shortens it in adults, and the agents tried, including thymic peptides, keratinocyte growth factor, growth hormone and sex steroid blockade, did not produce a treatment.\n\nThe honest reading is that this failed partly on biology and partly on design. Thymic output and repertoire diversity are research measures that no regulator has accepted as endpoints, and infection rates need trials larger than this population easily supports. So the field has neither a surrogate it is allowed to use nor a clinical endpoint it can afford.\n\nThe work splits in two. The regulatory half is to qualify an immune-recovery measure, by showing in existing transplant cohorts that it predicts infection and vaccine response well enough to be used as a trial endpoint. The biological half is then to test the candidates, old and new, against it. Doing the second without the first is what has already been tried.","asOf":"2026-10-02","links":[{"label":"Cordonnier et al., Vaccination of haemopoietic stem cell transplant recipients: ECIL 7 guidelines (Lancet Infectious Diseases 2019)","url":"https://doi.org/10.1016/S1473-3099(18)30600-5"}],"tags":["rejuvenation","survivorship","open-problem","immune"],"related":["rejuv-tx-immune-reconstitution-timeline","rejuv-tx-revaccination","rejuv-frontier-immune-reconstitution","rejuv-tx-b-cell-aplasia-and-immunoglobulin","rejuvenation-roadmap"],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["rejuv-agenda-thymus-does-not-regrow","b-biomarker-validation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"An intervention that restores thymic output in adults after transplant or intensive therapy will shorten the period of infection susceptibility and improve vaccine responses, and an immune-recovery measure can be qualified well enough to demonstrate that without a trial powered on infections alone.","rationale":"The transplant facet of this corpus states that there is no randomised evidence that any intervention accelerates thymic recovery in adults, and that the agents trialled for it have not produced a treatment in routine use. Normal cell counts do not mean a normal repertoire, and repertoire measurement is a research tool rather than a clinical test. Everything currently done is substitution: prophylaxis, immunoglobulin replacement and revaccination.","test":"First, an endpoint-qualification study in existing transplant cohorts linking T-cell receptor excision circles and repertoire diversity to subsequent infections and vaccine responses. Then a randomised trial of a candidate against that qualified endpoint with infection and vaccine response as co-secondaries.","maturity":"preclinical-evidence","actor":"research","cost":"large","horizonYears":10},{"id":"idea-crc-peritoneal-disease-found-early-and-treated-in-networks","kind":"idea","name":"Find peritoneal spread while it is still small, and run complete cytoreduction through networks rather than adding heated chemotherapy","aka":[],"tldr":"Bowel cancer that has seeded the lining of the abdomen responds badly to drugs but well to a complete operation, and the heated chemotherapy that everyone added turned out to do nothing. What decides the outcome is whether the disease is found while it is still limited and whether the patient reaches a centre that can remove all of it.","summary":"Verwaal's randomised trial put median survival at 22.3 against 12.6 months with cytoreduction and heated intraperitoneal oxaliplatin, at 8 percent treatment-related mortality, and its own subgroup analysis showed the result belonged to patients with fewer than six of seven abdominal regions involved and to macroscopically complete resections. PRODIGE 7 then randomised the heated chemotherapy away in 265 patients who had all had complete cytoreduction: 41.7 against 41.2 months, hazard ratio 1.00, with more grade 3 complications at 60 days in the heated arm.\n\nWhat that leaves is a surgical result gated by selection. Both trials enrolled patients under 70 with a Peritoneal Cancer Index of 25 or less; the index at presentation is the single strongest determinant of whether complete cytoreduction is possible, and it is a function of how early the peritoneal spread is found. Cross-sectional imaging is poor at low-volume peritoneal disease, and most of it is discovered at an operation done for another reason.","asOf":"2026-09-24","links":[{"label":"Quénet et al.: PRODIGE 7 (Lancet Oncol 2021)","url":"https://europepmc.org/article/MED/33476595"},{"label":"Verwaal et al.: cytoreduction and HIPEC (J Clin Oncol 2003)","url":"https://europepmc.org/article/MED/14551293"}],"tags":["colorectal-evidence"],"related":["colorectal-roadmap","surgery-roadmap"],"cancers":["colorectal"],"sections":["surgery","diagnostics"],"technologies":["hipec","mrd-testing","liquid-biopsy","ct","mri"],"targets":[],"drugs":["oxaliplatin","folfox"],"companies":[],"institutions":[],"pathways":[],"terms":["ctdna","mrd"],"trials":[],"people":[],"bottlenecks":["b-care-fragmentation","b-early-detection","b-surgery-radiation-innovation","b-negative-results"],"keyPapers":["paper-quenet-prodige-7-hipec-peritoneal-colorectal-lancet-oncol-2021","paper-verwaal-cytoreduction-hipec-peritoneal-colorectal-jco-2003"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A structured surveillance pathway for patients at high risk of peritoneal recurrence (T4, perforated, mucinous or signet-ring primaries, positive peritoneal cytology) using ctDNA and diagnostic laparoscopy rather than cross-sectional imaging alone increases the proportion diagnosed with a Peritoneal Cancer Index below 10, and thereby the proportion undergoing complete cytoreduction, without increasing the number of futile laparotomies.","rationale":"Complete cytoreduction, not the intraperitoneal chemotherapy, produces the survival; the Peritoneal Cancer Index at diagnosis determines whether complete cytoreduction is achievable; and current imaging misses low-volume peritoneal disease, so patients present past the threshold at which the one effective treatment can be offered.","test":"A randomised trial of structured surveillance with second-look laparoscopy and ctDNA against standard imaging follow-up in high-risk resected patients, with the proportion undergoing complete cytoreduction as the primary endpoint and overall survival, futile laparotomy rate and quality of life as secondary outcomes; networked referral so the operation happens in designated centres regardless of where surveillance occurs.","maturity":"early-clinical","actor":"clinic","cost":"medium","horizonYears":6},{"id":"idea-tr2-combo-dose-matrix","kind":"idea","name":"Find the lowest effective doses of both drugs in a combination, not the highest tolerated","aka":[],"tldr":"Combination trials usually keep one drug at full dose and push the other as high as patients can bear. Testing a grid of dose pairs would find combinations that work at lower, safer doses.","summary":"Project Optimus asks for dose optimisation of single agents; combinations remain largely dosed by escalating the new agent onto a fixed backbone. Model-based combination designs (BOIN-COMB, Bayesian optimal interval for drug combinations, and exposure-response modelling) can explore a two-dimensional dose grid and pick the pair with the best benefit-to-toxicity ratio. The proposal is regulatory expectation that registrational combination trials justify both doses with such data.","asOf":"2026-09-08","links":[{"label":"FDA Project Optimus","url":"https://www.fda.gov/about-fda/oncology-center-excellence/project-optimus"}],"tags":[],"related":["ild-overlap-caution"],"cancers":[],"sections":[],"technologies":["adc","checkpoint-inhibitor"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-combination-space","b-dose-optimisation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Combinations dosed from a two-dimensional optimisation will have at least 30% lower grade 3 or worse toxicity and non-inferior response rates compared with combinations dosed by conventional escalation on a fixed backbone.","rationale":"Many targeted-agent combinations (PI3K plus endocrine, MEK plus BRAF plus PD-1) failed on toxicity rather than efficacy. Overlapping toxicity is a dose problem that a matrix design can solve.","test":"Re-run dose selection for one toxic doublet (for example an ADC plus a checkpoint inhibitor) using a dose-matrix design in 60 patients and compare tolerability and response against the registrational dose.","maturity":"early-clinical","actor":"regulator","cost":"medium","horizonYears":3},{"id":"idea-bio1-drug-exposure-sanctuary-mapping","kind":"idea","name":"Find the parts of a tumour the drug never reaches","aka":[],"tldr":"Cells that receive only a small amount of a drug survive and adapt. Measuring where inside a tumour the drug actually reaches would show where resistance is being bred.","summary":"Sub-therapeutic exposure regions, created by poor perfusion, high interstitial pressure and dense stroma, are where selection for resistance is strongest. Imaging mass spectrometry on resected specimens, microdose PET with labelled analogues and intratumoural microdialysis can map drug concentration spatially. Linking these maps to regional clonal composition would show whether resistant clones arise preferentially in low-exposure zones.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Acquired resistance to every therapy): Soria et al., Osimertinib in untreated EGFR-mutated NSCLC (FLAURA, NEJM 2018)","url":"https://doi.org/10.1056/NEJMoa1713137"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["proteomics","pet","single-cell-spatial"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["resistance"],"trials":[],"people":[],"bottlenecks":["b-resistance","b-tumor-heterogeneity","b-dose-optimisation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Resistant subclones are enriched in tumour regions with the lowest measured drug concentration, establishing under-exposure rather than intrinsic biology as a major driver of resistance.","rationale":"Antibiotic resistance evolves fastest in concentration gradients, an experimentally demonstrated principle; tumours plausibly create the same gradients but the measurement is rarely made.","test":"Neoadjuvant window study: dose before surgery, then perform imaging mass spectrometry and region-matched sequencing on the resected tumour to test the spatial association.","maturity":"speculative","actor":"research","cost":"medium","horizonYears":5},{"id":"idea-tr1-duffy-null-neutrophil-threshold","kind":"idea","name":"Fix the neutrophil count rule that excludes many people of African ancestry","aka":[],"tldr":"A majority of people of West African ancestry carry the Duffy-null variant, which lowers baseline neutrophil counts without raising infection risk. Trials apply a single neutrophil cut-off that wrongly labels them unfit, so protocols should use Duffy-specific thresholds; Duffy status is a cheap blood test.","summary":"The Duffy-null phenotype (ACKR1 rs2814778 CC), carried by a majority of people of West African ancestry, is associated with lower baseline neutrophil counts without increased infection risk. Protocols would use Duffy-status-specific absolute neutrophil count thresholds (or exclude on infection history rather than ANC alone), and dose-modification rules for neutropenia would be reinterpreted accordingly. Duffy status is a cheap blood test.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Trials do not represent the people who get cancer): Loree et al., Disparity of race reporting and representation in trials leading to cancer drug approvals (JAMA Oncology 2019)","url":"https://doi.org/10.1001/jamaoncol.2019.1870"}],"tags":[],"related":[],"cancers":["prostate","multiple-myeloma","tnbc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-diversity","b-trial-enrolment"],"keyPapers":["paper-loree-jama-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Adopting Duffy-aware ANC thresholds will remove a leading cause of screen failure among Black patients in oncology trials and will not increase febrile neutropenia among those enrolled under the adjusted threshold.","rationale":"Retrospective analyses attribute a substantial share of Black patients' trial ineligibility and chemotherapy dose reductions to the standard ANC cut-off, and the Duffy-null association with benign neutropenia is well established in haematology.","test":"A sponsor adopts Duffy-aware thresholds across its solid-tumour trials for two years; compare Black patient screen-failure rates and febrile neutropenia among those newly eligible against prior protocols.","maturity":"early-clinical","actor":"industry","cost":"small","horizonYears":1},{"id":"lymphoma-ev-fixed-duration-chemotherapy-free-first-line","kind":"idea","name":"Fixed-duration, chemotherapy-free first-line treatment for the indolent lymphomas","aka":["Chemotherapy-free first line in follicular and mantle cell lymphoma","Time-limited bispecific antibody therapy"],"tldr":"Several treatments now work without chemotherapy, but most are given until the disease comes back. Giving them for a fixed time and stopping is the version patients would choose.","summary":"Two trials now recruiting bear directly on it: the National Cancer Institute comparison of fixed-duration mosunetuzumab against rituximab in low tumour burden follicular lymphoma, and the European trial of mosunetuzumab with lenalidomide in relapsed marginal zone lymphoma. Neither is designed with time off treatment as a primary endpoint, which is the gap. The payer argument is the same as the patient argument here, which is unusual and worth using.","asOf":"2026-10-01","links":[],"tags":["lymphoma-evidence"],"related":["lymphoma-roadmap"],"cancers":["follicular-lymphoma","marginal-zone-lymphoma","mantle-cell-lymphoma","non-hodgkin-lymphoma"],"sections":["immunotherapy","targeted-therapy"],"technologies":["bispecific-antibody","t-cell-engager"],"targets":["cd20","cd3","btk"],"drugs":["mosunetuzumab","odronextamab","ibrutinib","acalabrutinib","rituximab","lenalidomide"],"companies":[],"institutions":[],"pathways":[],"terms":["lymphoma-tx-maintenance","watchful-waiting"],"trials":["mosun-lbt-fl","mosun-len-mzl","enrich","relevance"],"people":[],"bottlenecks":["b-toxicity-qol","b-drug-pricing","b-patient-voice"],"keyPapers":["paper-enrich-ibrutinib-rituximab-mantle-cell-lancet-2025","paper-elm-2-odronextamab-follicular-ann-oncol-2024","paper-echo-acalabrutinib-bendamustine-rituximab-mantle-cell-jco-2025"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A fixed-duration, chemotherapy-free first-line regimen in follicular, marginal zone and mantle cell lymphoma achieves progression-free survival comparable to continuous or chemotherapy-containing treatment, with lower cumulative toxicity, lower cost and more time off treatment.","rationale":"ENRICH showed that ibrutinib with rituximab beats immunochemotherapy in older mantle cell lymphoma, but ibrutinib continues until progression. SHINE and ECHO both gained progression-free survival with indefinite Bruton tyrosine kinase inhibition and neither extended life. Mosunetuzumab is given for a fixed duration and odronextamab until progression, with complete response rates of 73.4 per cent for the latter in relapsed follicular lymphoma. RELEVANCE already showed a chemotherapy-free first line can match immunochemotherapy. The open question is whether stopping is safe.","test":"Randomise fixed-duration against continuous therapy within the same chemotherapy-free backbone, with retreatment at progression permitted in the fixed-duration arm, and measure time to second progression or next treatment rather than first progression. Co-primary endpoints should include total months on treatment and patient-reported outcomes, because those are the quantities the strategy is meant to change.","maturity":"being-tested-at-scale","actor":"research","cost":"large","horizonYears":6},{"id":"idea-bio2-cxcr4-mobilise-then-kill","kind":"idea","name":"Flush dormant cells out of bone marrow, then kill them","aka":[],"tldr":"Sleeping cancer cells hide in bone marrow where drugs cannot reach them. Pushing them into the bloodstream on purpose, then treating, might clear them.","summary":"Disseminated tumour cells occupy the CXCL12-CXCR4 haematopoietic niche, which shields them from chemotherapy. Plerixafor is an approved CXCR4 antagonist used to mobilise stem cells. A deliberate mobilise-then-treat schedule (plerixafor followed within a day by an antibody-drug conjugate or T-cell engager while cells are in circulation) is testable with agents that already exist.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Metastasis is understood least and studied last): Dillekås et al., Are 90% of deaths from cancer caused by metastases? (Cancer Medicine 2019)","url":"https://doi.org/10.1002/cam4.2474"}],"tags":[],"related":[],"cancers":["breast-hr-positive","tnbc"],"sections":[],"technologies":["adc","t-cell-engager","mrd-testing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["mrd"],"trials":[],"people":[],"bottlenecks":["b-metastasis-biology","b-dormancy-mrd"],"keyPapers":["paper-dillekas-cancer-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Plerixafor-induced mobilisation followed promptly by an antigen-directed agent reduces bone marrow disseminated tumour cell counts by at least 80% in patients who have detectable cells, versus the agent alone.","rationale":"The same manoeuvre improves chemosensitivity in acute myeloid leukaemia trials of CXCR4 blockade. If niche protection is why adjuvant therapy fails to clear disseminated cells, breaking the niche should be measurable directly in a marrow aspirate.","test":"A single-arm mechanistic trial in breast cancer patients with marrow-positive disseminated cells: serial aspirates and CTC counts before and after plerixafor plus an approved ADC. Kill the idea if counts do not fall.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":7},{"id":"idea-fus-plus-adc-glioma","kind":"idea","name":"Focused-ultrasound BBB opening to deliver ADCs and radioligands to glioma","aka":[],"tldr":"Brain tumours have targets that ADCs could hit, but antibodies cannot cross the barrier. Open the barrier with ultrasound first.","summary":"Depatuxizumab mafodotin (EGFR ADC) failed in INTELLANCE-1 partly through poor CNS penetration. Focused ultrasound raises antibody delivery several-fold in humans (Insightec, Carthera trials). Combining BBB opening with EGFR/EGFRvIII or B7-H3 ADCs, or with 177Lu/225Ac radioconjugates, is untested clinically.","asOf":"2026-09-06","links":[{"label":"Sonabend et al., Repeated blood-brain barrier opening with an implantable ultrasound device for delivery of albumin-bound paclitaxel in glioblastoma (Lancet Oncology 2023)","url":"https://doi.org/10.1016/S1470-2045(23)00112-2"}],"tags":[],"related":[],"cancers":["glioblastoma"],"sections":[],"technologies":["bbb-focused-ultrasound","adc","radioimmunotherapy"],"targets":["egfr","b7h3"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["blood-brain-barrier"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-sonabend-lancet-oncol","paper-egfr-glioblastoma-mol-oncol-2018","paper-egfr-glioblastoma-sci-signal-2009","paper-b7-h3-glioblastoma-int-j-biol-sci-2023"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Opening the blood-brain barrier with focused ultrasound immediately before ADC or radioconjugate infusion achieves therapeutic intratumoural concentrations and objective responses in recurrent glioblastoma.","rationale":"Mechanism-agnostic delivery boost; targets (EGFR, B7-H3, IL13Rα2) are validated; payload potency compensates for limited volume.","test":"Phase 1 with paired pre/post-opening tumour sampling at re-resection measuring ADC concentration; expansion cohort with RANO response.","maturity":"preclinical-evidence"},{"id":"idea-data-registry-follow-up-of-trial-participants","kind":"idea","name":"Follow every trial participant for 30 years through registry linkage","aka":[],"tldr":"Trials stop following patients after a few years, so late side effects and late relapses are missed. Link trial participants to national records so follow-up continues automatically for decades.","summary":"Late effects of cancer treatment (second cancers, cardiac disease, endocrine failure) appear decades later, long after trials close. The Childhood Cancer Survivor Study shows the value of long follow-up but relies on costly active contact. The proposal requires consent for registry linkage in every publicly funded trial and funds automated linkage of trial participants to cancer, death and hospital records for 30 years, with pooled analysis across trials.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Weak real-world evidence and registries): Gyawali, Hey & Kesselheim, Assessment of the clinical benefit of cancer drugs receiving accelerated approval (JAMA Intern Med 2019)","url":"https://doi.org/10.1001/jamainternmed.2019.0462"}],"tags":[],"related":["idea-data-trial-to-registry-bridge"],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":["childrens-oncology-group","swog","ecog-acrin"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-real-world-evidence","b-survivorship","b-trial-design"],"keyPapers":["paper-gyawali-jama-intern-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Passive registry follow-up will capture more than 95 percent of deaths and second cancers in trial participants at a small fraction of the cost of active follow-up, and will detect late toxicity signals for at least one widely used regimen within five years.","rationale":"Nordic trial groups already do this; the survival curves for several adjuvant trials were extended by a decade at negligible cost through registry linkage.","test":"Link participants from five completed cooperative-group trials to registries; compare completeness and cost with the trials' original active follow-up; report late events.","maturity":"early-clinical","actor":"research","cost":"small","horizonYears":3},{"id":"idea-bio1-evolution-forecasting","kind":"idea","name":"Forecast the next resistance mutation like the weather","aka":[],"tldr":"Flu vaccines are chosen by predicting which virus strains will dominate next season. The same forecasting maths could predict which resistance mutation a patient's tumour will develop next.","summary":"Evolutionary forecasting methods from influenza and bacterial resistance estimate the fitness of circulating variants from their frequency trajectories. Applied to longitudinal ctDNA and to population-level databases of resistance under each drug, they could give per-patient probabilities of specific next-step mechanisms. Forecasts would be scored prospectively, as in weather forecasting, to build calibrated models.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Tumour heterogeneity and clonal evolution): Gerlinger et al., Intratumor heterogeneity and branched evolution (NEJM 2012)","url":"https://doi.org/10.1056/NEJMoa1113205"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["liquid-biopsy","ai-drug-design"],"targets":[],"drugs":["osimertinib","sotorasib"],"companies":[],"institutions":[],"pathways":[],"terms":["resistance"],"trials":[],"people":[],"bottlenecks":["b-tumor-heterogeneity","b-resistance","b-ai-validation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A forecasting model trained on longitudinal ctDNA from patients on a given targeted drug predicts the dominant resistance mechanism at progression with calibrated accuracy well above the population base rate.","rationale":"Resistance mechanisms under a given drug are strongly constrained (a handful of routes dominate for osimertinib, alectinib, or sotorasib), and their early emergence is visible in serial plasma. Predictability is what makes pre-emptive combination possible.","test":"Train on serial plasma from completed trials, publish locked forecasts for a prospective cohort, and score them against observed progression biopsies; a Brier score better than base rate confirms.","maturity":"speculative","actor":"data","cost":"small","horizonYears":3},{"id":"idea-moon-caregiver-in-the-plan","kind":"idea","name":"Formal caregiver assessment and training written into every treatment plan","aka":[],"tldr":"The person looking after a cancer patient at home is assessed, trained (medicines, symptoms, when to call) and supported as part of the plan, not left to work it out.","summary":"Informal caregivers deliver most cancer care and report high distress, financial loss and health deterioration; caregiver competence predicts patient admissions. The proposal is a caregiver assessment at treatment start (capacity, health, needs), a short skills programme for home management, and a named contact, recorded in the patient's plan with caregiver-reported outcomes tracked.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Patients lack understanding, navigation and agency): Basch et al., Overall survival results of a trial assessing patient-reported outcomes for symptom monitoring during routine cancer treatment (JAMA 2017)","url":"https://doi.org/10.1001/jama.2017.7156"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-patient-voice","b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Caregiver assessment and training reduce patient emergency admissions and caregiver depression scores and increase completion of oral therapies managed at home.","rationale":"Oral and outpatient therapy has moved care into the home without moving the training; dementia and stroke care have shown caregiver programmes are effective.","test":"Randomised trial of caregiver programme versus usual care for patients starting oral or outpatient regimens; endpoints admissions, adherence, caregiver burden.","maturity":"early-clinical","actor":"clinic","cost":"small","horizonYears":2},{"id":"idea-acc-primary-care-shared-care-agreements","kind":"idea","name":"Formal shared-care agreements between oncology and family doctors, with same-day e-consult","aka":[],"tldr":"Family doctors often do not know who is responsible for a cancer patient's blood pressure, diabetes or new symptom. Written agreements plus a same-day electronic question line to the oncologist would fill the gap.","summary":"During active treatment, primary care is often sidelined; after treatment, oncology withdraws and primary care is unclear about what to monitor. Formal shared-care agreements defining who manages what, combined with electronic consultation channels with a same-day response target, have improved coordination in other chronic diseases. Applying them systematically in oncology would reduce emergency visits and duplicated or missed care.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Fragmented care and guideline gaps): Hanna et al., Mortality due to cancer treatment delay: systematic review and meta-analysis (BMJ 2020)","url":"https://doi.org/10.1136/bmj.m4087"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-care-fragmentation","b-aging-comorbidity"],"keyPapers":["paper-hanna-bmj"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Practices under shared-care agreements with e-consult access will reduce unplanned emergency attendances of their cancer patients by at least 15% and increase management of comorbidities to target.","rationale":"Ambiguity of responsibility is a documented cause of missed care in cancer; explicit agreements resolve it at low cost.","test":"A cluster-randomised trial across 60 primary care practices with emergency attendance, comorbidity control, and clinician satisfaction as endpoints.","maturity":"early-clinical","actor":"clinic","cost":"small","horizonYears":2},{"id":"idea-tr2-ctdna-mrd-qualification","kind":"idea","name":"Formally qualify tumour-DNA blood tests as a surrogate endpoint for adjuvant trials","aka":[],"tldr":"If a blood test reliably shows whether cancer will come back after surgery, trials could use it instead of waiting years for relapse. Regulators have a process to bless such a test; oncology should use it.","summary":"FDA's Biomarker Qualification Program creates a drug-independent, context-of-use qualification for biomarkers. ctDNA clearance after adjuvant therapy correlates strongly with recurrence in colorectal, bladder and lung cancer, and trial-level meta-analysis is becoming possible as ctDNA-guided trials report. A consortium submission to qualify ctDNA clearance as a reasonably likely surrogate for disease-free survival in defined settings would let adjuvant trials read out in one to two years rather than five.","asOf":"2026-09-08","links":[{"label":"FDA Biomarker Qualification Program","url":"https://www.fda.gov/drugs/drug-development-tool-ddt-qualification-programs/biomarker-qualification-program"}],"tags":[],"related":["idea-ctdna-guided-adjuvant-crc","ctdna-mrd-to-adjuvant"],"cancers":[],"sections":[],"technologies":["mrd-testing","liquid-biopsy"],"targets":[],"drugs":["signatera"],"companies":[],"institutions":[],"pathways":[],"terms":["ctdna","mrd"],"trials":["imvigor011","dynamic","circulate-japan"],"people":[],"bottlenecks":["b-biomarker-validation","b-dormancy-mrd"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Trial-level correlation between ctDNA clearance rate and disease-free survival hazard ratio across adjuvant trials will be strong enough (R squared above 0.7) to support qualification in at least one tumour type by 2029.","rationale":"Pathological complete response and MRD in haematological cancers have been accepted for accelerated approval on similar reasoning; ctDNA has cleaner biology and is measured uniformly.","test":"Pool patient- and trial-level data from completed ctDNA-guided adjuvant trials (DYNAMIC, CIRCULATE, IMvigor011 and others) and run the surrogate validation analyses required for qualification.","maturity":"early-clinical","actor":"regulator","cost":"medium","horizonYears":4},{"id":"idea-fund-fast-grants-oncology","kind":"idea","name":"Forty-eight-hour small grants for bold experiments in neglected cancers","aka":[],"tldr":"Fast grants for oncology would be a fund that decides within two days on small grants for quick, decisive experiments in cancers or questions that mainstream funders neglect, modelled on the pandemic-era Fast Grants.","summary":"Fast Grants during COVID-19 funded hundreds of projects with 48-hour decisions and a one-page application; several delivered results, and recipients reported that speed, not just money, changed what they attempted. A cancer version would target neglected cancers and unfashionable questions (cachexia, metastasis models, surgical technique, repurposed drugs) with awards of $10,000 to $500,000, pre-registration of the key experiment, and a public results record including failures.","asOf":"2026-09-08","links":[{"label":"Fast Grants","url":"https://fastgrants.org/"}],"tags":[],"related":["idea-fund-neglected-cancer-lottery","idea-fund-phase-zero-fund"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-funding-allocation","b-translational-valley"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Fast, small grants targeted at neglected areas produce at least as many follow-on funded projects and published results per dollar as conventional awards, with a median time from idea to first data of under six months.","rationale":"Fast Grants surveys found that most recipients would change their research direction if funding were flexible and fast; conventional cycles take a year from idea to money. Small, quick tests are the right instrument for exploratory work in areas where there is little prior art to justify a big grant.","test":"Run the fund for two years, tracking time to first result, publication and follow-on funding rates, and compare with a matched sample of conventional small grants from the same funder.","maturity":"speculative","actor":"philanthropy","cost":"medium","horizonYears":2},{"id":"idea-bio2-prehabilitation-standard","kind":"idea","name":"Four weeks of training and nutrition before major cancer surgery, as standard","aka":[],"tldr":"Getting fitter and better nourished before an operation reduces complications and speeds recovery. It is cheap, but only a few hospitals do it.","summary":"Multimodal prehabilitation combining aerobic and resistance exercise, protein supplementation, anaemia correction and smoking cessation has reduced complications in randomised trials and meta-analyses of large abdominal cancer operations. Adoption is patchy because it requires service redesign rather than a product, and because delaying surgery by weeks feels counterintuitive.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Cachexia, toxicity and the limits of the patient): Fearon et al., Definition and classification of cancer cachexia (Lancet Oncology 2011)","url":"https://doi.org/10.1016/S1470-2045(10)70218-7"}],"tags":[],"related":["idea-exercise-as-adjuvant"],"cancers":["colorectal","esophageal","pancreatic"],"sections":[],"technologies":["exercise-oncology","geriatric-assessment"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-cachexia-supportive","b-care-fragmentation","b-survivorship"],"keyPapers":["paper-fearon-lancet-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"System-wide prehabilitation reduces major postoperative complications by a fifth and length of stay by a day, and increases the proportion of patients fit to receive adjuvant therapy on time.","rationale":"Postoperative complications delay or prevent adjuvant therapy, which affects cancer outcomes, so a perioperative intervention has oncological consequences. The components are all cheap and have independent evidence.","test":"A stepped-wedge implementation trial across a regional surgical network with complications, length of stay and adjuvant therapy delivery as endpoints, and a cost analysis.","maturity":"being-tested-at-scale","actor":"clinic","cost":"medium","horizonYears":4},{"id":"idea-reg-cart-outcomes-refund","kind":"idea","name":"Full refund for CAR-T if the patient has not responded at three months","aka":[],"tldr":"Health systems would pay for a $400,000 cell therapy only if it works. If the cancer has not responded by three months, the company refunds the price.","summary":"Italy's AIFA negotiated payment-by-result for tisagenlecleucel with instalments tied to response, and the US CMS Cell and Gene Therapy Access Model (launched 2025 for sickle cell disease) ties Medicaid payment to outcomes negotiated centrally. The proposal is to make a response-conditional refund the default reimbursement structure for oncology CAR-T and other one-time cell therapies in public systems: full price paid at infusion, automatic full or majority refund if no complete or partial response is documented at 90 days in the treatment registry, with the registry rather than the manufacturer adjudicating.","asOf":"2026-09-08","links":[{"label":"CMS Cell and Gene Therapy Access Model (page moved; nearest live section)","url":"https://www.cms.gov/priorities/innovation/innovation-models/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["car-t"],"targets":[],"drugs":["axicabtagene-ciloleucel","ciltacabtagene-autoleucel"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-drug-pricing","b-manufacturing-cell-therapy"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Response-conditional refunds reduce effective payer spend per durable responder by at least 25% relative to list price and increase the number of centres and countries offering CAR-T, without manufacturers withdrawing from participating markets.","rationale":"One-time therapies with a binary early response signal are the cleanest case for outcomes-based pricing; the transaction cost problem that defeated earlier schemes is solved when a registry already collects the outcome.","test":"Extend the CMS CGT Access Model or an equivalent national scheme to relapsed lymphoma and myeloma CAR-T for three years; compare spend per responder and patient volumes with fixed-price countries.","maturity":"being-tested-at-scale","actor":"payer","cost":"small","horizonYears":2},{"id":"idea-bio1-mandatory-progression-biopsy","kind":"idea","name":"Fund a biopsy at progression, every time, as standard care","aka":[],"tldr":"When a treatment stops working, the tumour is rarely re-sampled, so nobody learns why. Paying for a biopsy at that moment would build the missing map of resistance.","summary":"Resistance mechanisms are known for only a minority of progressions because the sample is never taken: reimbursement is unclear, the patient is unwell, and there is no trial slot. A funded pathway would pay for a paired tissue and plasma sample at every progression on a targeted agent, with rapid sequencing, a mechanism-matched treatment recommendation returned to the clinician, and deposition into a shared database.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Acquired resistance to every therapy): Soria et al., Osimertinib in untreated EGFR-mutated NSCLC (FLAURA, NEJM 2018)","url":"https://doi.org/10.1056/NEJMoa1713137"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["cgp","liquid-biopsy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["resistance","ctdna"],"trials":[],"people":[],"bottlenecks":["b-resistance","b-data-silos"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A funded resistance-biopsy pathway raises the proportion of progressions with a defined mechanism from a small minority to over half, and identifies an actionable alteration in a fifth of cases.","rationale":"Where such programmes exist in research settings, mechanism yield is high and actionable findings are common; the barrier is reimbursement and logistics rather than science.","test":"Coverage-with-evidence pilot in one health system for 1,000 progressions: measure mechanism yield, actionability, uptake of matched therapy and cost per actionable finding.","maturity":"early-clinical","actor":"payer","cost":"medium","horizonYears":3},{"id":"idea-reg-alpha-emitter-portfolio","kind":"idea","name":"Fund alpha emitters beyond actinium-225: lead-212, terbium-149 and astatine-211","aka":[],"tldr":"Almost every alpha cancer therapy in development relies on one scarce isotope. Developing several alternatives at once would stop the whole field waiting on a single supply chain.","summary":"Actinium-225 dominates targeted alpha therapy pipelines, but lead-212 (from thorium-228/radium-224 generators, used by Orano Med and Perspective Therapeutics), astatine-211 (cyclotron-produced, short half-life, suited to regional supply) and terbium-149 have complementary properties and independent supply routes. The proposal is a public-private programme that funds isotope-agnostic chelator and linker chemistry, comparative dosimetry and small head-to-head clinical studies so that a given targeting ligand can be paired with whichever alpha emitter is available, and that de-risks generator and cyclotron capacity for each.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Manufacturing cost and time for living and radioactive medicines): Hernandez, Prasad & Gellad, Total costs of chimeric antigen receptor T-cell immunotherapy (JAMA Oncology 2018)","url":"https://doi.org/10.1001/jamaoncol.2018.0977"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["targeted-alpha-therapy"],"targets":[],"drugs":[],"companies":["orano-med","perspective-therapeutics"],"institutions":[],"pathways":[],"terms":["alpha-vs-beta"],"trials":[],"people":[],"bottlenecks":["b-manufacturing-cell-therapy"],"keyPapers":["paper-hernandez-jama-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Within five years at least two alpha emitters other than actinium-225 reach late-stage trials with GMP supply exceeding clinical demand, and the proportion of alpha therapy trials delayed by isotope supply falls below 10%.","rationale":"Diversifying supply has repeatedly been cheaper than expanding a single constrained route; lead-212 generators are already in clinical use and astatine-211 chemistry has matured at several centres.","test":"Award funding to three ligand programmes to produce matched actinium-225, lead-212 and astatine-211 versions and compare biodistribution, dosimetry and manufacturability in first-in-human studies.","maturity":"preclinical-evidence","actor":"philanthropy","cost":"large","horizonYears":5},{"id":"idea-reg-african-medicines-agency-oncology","kind":"idea","name":"Fund an oncology joint assessment unit inside the African Medicines Agency","aka":[],"tldr":"Africa's new continental medicines agency could assess cancer drugs once for 55 countries. It needs oncology reviewers and a reliance rule to do it.","summary":"The African Medicines Agency is becoming operational, building on AVAREF and regional harmonisation initiatives (EAC, SADC). Oncology medicines are a small share of African registrations and most national agencies lack oncology reviewers. The proposal is a philanthropically funded oncology unit within AMA running continental joint assessments, relying on WHO-listed authority reports, with member states committing to national decisions within 60 days of an AMA recommendation. The WHO/St Jude childhood cancer medicines platform provides demand.","asOf":"2026-09-08","links":[{"label":"African Medicines Agency (page moved; nearest live section)","url":"https://au.int/en/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-regulatory-fragmentation","b-global-access"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Oncology medicines assessed through the AMA unit are registered in at least 20 African countries within one year of recommendation, compared with a current pattern where most new oncology drugs are registered in fewer than five African countries five years after first global approval.","rationale":"Joint assessment has already cut registration times in East Africa; the missing pieces are oncology expertise and a binding timeline. Pooled assessment also makes small markets worth filing in.","test":"Fund the unit for five years and track the number of countries registering each assessed oncology medicine and the median time to registration.","maturity":"speculative","actor":"philanthropy","cost":"medium","horizonYears":5},{"id":"idea-data-wikipedia-oncology-editors","kind":"idea","name":"Fund expert editors for the cancer pages of Wikipedia and Wikidata","aka":[],"tldr":"Wikipedia's medical pages receive billions of views and its cancer pages are among the most read, yet they are often out of date on treatment. Funding a standing team of oncology editors and translators, as Cochrane and WHO have done with Wikimedia, would keep them current against living guidelines and add structured trial and drug identifiers to Wikidata.","summary":"Wikipedia's medical pages receive billions of views; cancer pages are among the most read and are often out of date on treatment. The proposal funds a small standing team of oncology editors and translators (as Cochrane and WHO have done in partnership with Wikimedia) to maintain cancer articles against living guidelines, add structured data to Wikidata (linking to trial and drug identifiers), and measure accuracy over time.","asOf":"2026-09-08","links":[{"label":"WikiProject Medicine","url":"https://en.wikipedia.org/wiki/Wikipedia:WikiProject_Medicine"}],"tags":[],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-knowledge-diffusion","b-misinformation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Funded editing will raise the accuracy and currency of the 200 most-read cancer articles to guideline-concordant status and reduce the presence of unproven therapies presented as effective.","rationale":"Cochrane-Wikipedia and WikiProject Medicine partnerships have improved article quality where sustained; cancer is the highest-traffic area without dedicated funding.","test":"Audit accuracy of the top 200 cancer articles against guidelines; fund editors for two years; re-audit and compare with untouched control articles.","maturity":"speculative","actor":"philanthropy","cost":"small","horizonYears":1},{"id":"idea-tr1-diverse-investigator-pipeline","kind":"idea","name":"Fund investigators from under-represented communities and community sites to lead trials","aka":[],"tldr":"Patients are more likely to join a trial when the doctor offering it looks like them or works in their community. Funding more such doctors to become trial leaders would change who is enrolled.","summary":"Career development awards, protected time and mentorship for oncologists from under-represented groups and those practising in community, rural and safety-net settings, tied to becoming principal investigators. Cooperative groups set targets for the share of PIs from these backgrounds. Evidence that racial concordance and community-based investigators raise minority enrolment is observational but consistent.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Trials do not represent the people who get cancer): Loree et al., Disparity of race reporting and representation in trials leading to cancer drug approvals (JAMA Oncology 2019)","url":"https://doi.org/10.1001/jamaoncol.2019.1870"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["nci","asco","aacr"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-diversity","b-workforce"],"keyPapers":["paper-loree-jama-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Sites led by investigators from under-represented groups or based in community settings will enrol a higher share of minority and low-income participants, and increasing their number will shift network-level representativeness.","rationale":"Investigator distribution mirrors academic centre demographics; recruitment relationships run through clinicians. Workforce interventions have long lags but compound.","test":"Fund 50 awards over five years and compare enrolment demographics at awardees' sites with matched non-awardee sites.","maturity":"early-clinical","actor":"philanthropy","cost":"medium","horizonYears":5},{"id":"idea-moon-wikipedia-oncology-fellowships","kind":"idea","name":"Fund oncologists to maintain cancer articles on Wikipedia in many languages","aka":[],"tldr":"Wikipedia is the most-read medical reference on Earth. Pay expert editors to keep its cancer pages accurate, current and available in the languages most patients speak.","summary":"Cancer articles on Wikipedia receive enormous traffic and feed AI assistants and search results, but quality and currency vary and non-English coverage is thin. WikiProject Medicine coordinates volunteers. The proposal is funded fellowships for oncologists, pharmacists and translators to update the top 500 cancer articles against current guidelines, translate them into the twenty most-spoken languages, and maintain them, with the work tracked publicly.","asOf":"2026-09-08","links":[{"label":"WikiProject Medicine","url":"https://en.wikipedia.org/wiki/Wikipedia:WikiProject_Medicine"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-misinformation","b-knowledge-diffusion","b-global-access"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Fellowship-maintained articles score higher on expert quality review and are updated within months of guideline changes, and their translated versions capture a majority of non-English cancer page views.","rationale":"Where people actually read is where accuracy pays; the marginal cost of expert editing is tiny compared with its reach.","test":"Fund twenty fellows for one year; compare quality scores, currency and page views for maintained versus unmaintained articles.","maturity":"early-clinical","actor":"philanthropy","cost":"small","horizonYears":1},{"id":"idea-reg-regulator-ready-repurposing-dossiers","kind":"idea","name":"Fund regulator-ready evidence dossiers for the 20 best-supported off-patent drugs","aka":[],"tldr":"The evidence for old drugs against cancer is scattered across hundreds of papers. Assembling it into the format regulators and funders need is cheap and would speed decisions.","summary":"The Anticancer Fund's ReDO_DB and similar efforts catalogue candidates but stop short of the structured, regulator-grade dossiers (preclinical summary, pharmacology, safety in the target population, systematic review of clinical signals, proposed trial design) that a funder or a third-party label filing needs. The proposal is a funded programme, with methodologists and regulatory writers, that produces and publishes open dossiers for the 20 candidates with the strongest evidence, updated annually, each ending with a prioritised trial proposal and a regulatory strategy.","asOf":"2026-09-08","links":[{"label":"ReDO_DB (page moved; nearest live section)","url":"https://www.anticancerfund.org/en/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-generic-repurposing","b-knowledge-diffusion"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Within three years, at least half of the dossiers lead to a funded trial or a regulatory or guideline submission, compared with a small minority of candidates in the current catalogue.","rationale":"Funders and regulators act on well-organised evidence; the marginal cost of a dossier is trivial against the cost of the trial it enables, and public dossiers prevent duplicated effort across countries.","test":"Produce the first ten dossiers, circulate to funders and regulators, and track downstream trial funding and submissions against ten matched candidates without dossiers.","maturity":"early-clinical","actor":"philanthropy","cost":"small","horizonYears":2},{"id":"idea-moon-hair-preservation-for-all","kind":"idea","name":"Fund scalp cooling and hair-preserving measures for every alopecia-inducing regimen","aka":[],"tldr":"Losing hair is one of the most distressing side-effects of chemotherapy and can often be prevented with a cooling cap. Make it routinely available and paid for.","summary":"Scalp cooling reduces chemotherapy-induced alopecia in randomised trials and is cleared by regulators, yet availability depends on charity, geography and unit culture. The proposal is payer coverage and unit-level capacity for scalp cooling for all patients receiving alopecia-inducing regimens who want it, plus trials of adjunctive topical agents, with hair preservation and body-image outcomes measured in registries.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Toxicity and quality of life are undervalued): Di Maio et al., Symptomatic toxicities experienced during anticancer treatment: agreement between patient and physician reporting (JCO 2015)","url":"https://doi.org/10.1200/JCO.2014.57.9334"}],"tags":[],"related":[],"cancers":[],"sections":["rejuvenation"],"technologies":["scalp-cooling"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol"],"keyPapers":["paper-di-maio-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Universal availability raises use to over half of eligible patients and reduces refusal of alopecia-inducing regimens and treatment-related distress.","rationale":"Alopecia influences treatment choice and self-image; the intervention exists and is safe, and the barrier is purely organisational and financial.","test":"Payer covers scalp cooling in one region; measure uptake, hair preservation rates and refusal of recommended chemotherapy versus a matched region.","maturity":"being-tested-at-scale","actor":"payer","cost":"small","horizonYears":2},{"id":"idea-crc-exercise-as-a-funded-treatment","kind":"idea","name":"Fund structured exercise after colon cancer surgery as a treatment, because a randomised trial says it works as well as a drug","aka":[],"tldr":"A three-year supervised exercise programme after chemotherapy cut recurrence and death by roughly a third in 889 patients, an effect the size of adjuvant chemotherapy. No health system has a funding line for it.","summary":"CHALLENGE randomised 889 patients with resected colon cancer who had completed adjuvant chemotherapy to a structured exercise programme or health-education materials over three years. At a median 7.9 years, disease-free survival favoured exercise with a hazard ratio of 0.72 (five-year disease-free survival 80.3 against 73.9 percent), and overall survival with a hazard ratio of 0.63 (eight-year overall survival 90.3 against 83.2 percent). Musculoskeletal adverse events were more common with exercise (18.5 against 11.5 percent).\n\nThe trial took 15 years to enrol because no commercial sponsor benefits from the result, and the intervention is a supervised programme with a behaviour-support consultant rather than advice to be more active. That is the gap: the evidence is now stronger than for several funded drugs in the same setting, and the implementation question, who employs the trainers and how patients are referred, has never been tested in a health system.","asOf":"2026-09-24","links":[{"label":"Courneya et al.: CHALLENGE (N Engl J Med 2025)","url":"https://europepmc.org/article/MED/40450658"}],"tags":["colorectal-evidence"],"related":["colorectal-roadmap","survivorship-roadmap","nutrition-lifestyle-roadmap"],"cancers":["colorectal","colon-cancer"],"sections":["supportive-care","nutrition-lifestyle","rejuvenation"],"technologies":["exercise-oncology"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-funding-allocation","b-prevention-adoption","b-incentive-misalignment"],"keyPapers":["paper-challenge-exercise-nejm-2025"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A funded, referral-based structured exercise service for patients completing adjuvant chemotherapy for colon cancer reproduces at least half of the CHALLENGE disease-free survival effect in routine practice, at a cost per quality-adjusted life year below the threshold used for adjuvant drugs in the same indication.","rationale":"The randomised effect size is comparable to adjuvant chemotherapy at a fraction of the drug cost and with reversible musculoskeletal rather than neurological harm; the only untested step is whether a health service can deliver the programme as the trial did.","test":"A stepped-wedge implementation trial across cancer centres, with adherence to the exercise prescription and three-year disease-free survival as co-primary endpoints, a pre-registered health-economic analysis, and equity of referral and completion by deprivation quintile as a reported outcome.","maturity":"early-clinical","actor":"payer","cost":"medium","horizonYears":4},{"id":"idea-cost-shorter-course-trials","kind":"idea","name":"Fund trials that test shorter courses of the most expensive adjuvant drugs","aka":[],"tldr":"The PERSEPHONE trial showed six months of trastuzumab after surgery is as good as twelve, halving the drug cost; no company will run such trials, so public funders and charities must.","summary":"PERSEPHONE (Earl et al., Lancet 2019) randomised 4,089 women with HER2-positive early breast cancer to six or twelve months of adjuvant trastuzumab and found four-year disease-free survival of 89.4% versus 89.8%, meeting non-inferiority, with less cardiotoxicity. Adjuvant durations for checkpoint inhibitors (one year), CDK4/6 inhibitors (two to three years) and PARP inhibitors (one year) were set without duration-finding studies. A dedicated de-escalation trial fund, on the model of the UK National Institute for Health and Care Research that paid for PERSEPHONE, would test the highest-spend adjuvant regimens.","asOf":"2026-09-10","links":[{"label":"Earl et al., Lancet 2019: PERSEPHONE","url":"https://doi.org/10.1016/S0140-6736(19)30650-6"}],"tags":[],"related":[],"cancers":["breast-her2-positive","breast-hr-positive"],"sections":[],"technologies":[],"targets":[],"drugs":["trastuzumab","pembrolizumab","abemaciclib","olaparib"],"companies":[],"institutions":["nci","cruk"],"pathways":[],"terms":[],"trials":["persephone"],"people":[],"bottlenecks":["b-dose-optimisation","b-drug-pricing","b-trial-design","b-incentive-misalignment"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"At least two of five adjuvant de-escalation trials will demonstrate non-inferiority, each saving more than a third of the drug cost for that indication.","rationale":"Manufacturers have no incentive to shorten courses; the payer has every incentive and the evidence base for adjuvant durations is thin.","test":"A funded portfolio of five randomised non-inferiority duration trials run through cooperative groups, with pre-registered margins and cost-effectiveness analyses.","maturity":"early-clinical","actor":"philanthropy","cost":"large","horizonYears":6},{"id":"idea-data-funded-living-systematic-reviews","kind":"idea","name":"Funded living systematic reviews for every major cancer indication","aka":[],"tldr":"Instead of a review that is out of date on publication, fund teams to keep one continuously updated review per cancer setting, adding each new trial as it appears.","summary":"Systematic reviews take a year and are outdated within another. Living systematic reviews with continuous search, AI-assisted screening and network meta-analysis have been sustained in COVID-19 and a few other areas. The proposal funds a living review per major indication (perhaps 60), each maintained by a small team using shared tooling, published as structured data feeding living guidelines.","asOf":"2026-09-08","links":[{"label":"COVID-NMA living evidence","url":"https://covid-nma.com/"}],"tags":[],"related":["pubmed-europepmc"],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-knowledge-diffusion"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Living reviews will incorporate new trial results within 30 days of publication and will be cited as the primary evidence source by guideline bodies for the covered indications within three years.","rationale":"The COVID-NMA living network meta-analysis updated weekly for years; the tooling (automated search, machine learning screening, standard extraction) has matured enough to run at lower cost per review.","test":"Fund ten living reviews for two years; measure update latency, cost per update, and guideline citation compared with conventional reviews in matched indications.","maturity":"early-clinical","actor":"philanthropy","cost":"medium","horizonYears":2},{"id":"idea-fund-surgeon-scientist-pathway","kind":"idea","name":"Funded research pathways for surgeon-scientists and radiation oncologist-scientists","aka":[],"tldr":"Almost no surgeons or radiation oncologists have time or funding to do research. Dedicated training awards with protected time would build the workforce that surgical and radiotherapy trials need.","summary":"A funded career pathway: integrated research years within surgical and radiation oncology training, career-development awards on the model of NIH K08/K23 but reserved for these specialties, protected time in the first faculty years and mentorship networks linked to the surgical and radiotherapy trials infrastructure. Surgeon-scientists are a shrinking fraction of NIH-funded investigators, and radiation oncology, though research-rich relative to its size, lacks trialists and translational scientists. Awards prioritise trial methodology, health services research and technology evaluation, the skills these fields lack most.","asOf":"2026-09-08","links":[{"label":"American College of Surgeons","url":"https://www.facs.org/"}],"tags":[],"related":["idea-fund-translational-fellowships","idea-fund-protected-time-physician-scientists","idea-fund-surgical-trials-network"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["asco","esmo"],"pathways":[],"terms":[],"trials":[],"people":["kevin-harrington","michael-baumann"],"bottlenecks":["b-surgery-radiation-innovation","b-workforce"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Reserved career awards increase the number of surgeons and radiation oncologists holding independent research funding by at least half within eight years and increase the number of surgical and radiotherapy trials led by awardees.","rationale":"Analyses of NIH funding show surgeon-scientists declining as a share of investigators and reporting lack of protected time as the main cause; specialty-reserved awards in other fields (for example emergency medicine and anaesthesia K12 programmes) have measurably increased research output.","test":"Fund fifty awards over five years and compare independent funding, trials led and retention in academia against a matched cohort of trainees without awards.","maturity":"speculative","actor":"research","cost":"medium","horizonYears":6},{"id":"idea-fund-open-results-bonus","kind":"idea","name":"Funder bonuses for releasing results and data within six months, negatives included","aka":[],"tldr":"Pay scientists a small bonus, added to their grant, when they post their results and data openly within six months of finishing an experiment, whether the result was positive or not.","summary":"Funders add a supplement (for example 5% of the award) paid on verified release of preprints, datasets and code within six months of the end of each funded aim, with an equal bonus for registered negative results. Unlike mandates, which are widely ignored without enforcement, bonuses are self-enforcing and visible. Academic secrecy before publication delays diffusion by one to two years and hides most negative preclinical findings entirely; a small financial reward changes the calculus for labs that currently see only risk in early release.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Secrecy and intellectual property block collaboration): Danchev et al., Evaluation of data sharing after implementation of the ICMJE data sharing statement requirement (JAMA Netw Open 2021)","url":"https://doi.org/10.1001/jamanetworkopen.2020.33972"}],"tags":[],"related":["idea-fund-academic-promotion-reform","idea-fund-trial-completion-bonus","idea-fund-scoop-protection-policy"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-ip-collaboration","b-knowledge-diffusion","b-negative-results"],"keyPapers":["paper-danchev-jama-netw-open"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Open-results bonuses raise the proportion of funded projects with preprints or data released within six months from a small minority to a majority within two years, with a measurable increase in reported negative results, at a cost under 5% of the portfolio.","rationale":"Behavioural experiments in science funding show that small, certain rewards change compliance more than rarely enforced mandates; the Gates Foundation and Wellcome open-access mandates achieved high compliance only when paired with funding for fees. Registered reports formats show negative results are published when the incentive structure allows.","test":"Randomise the bonus across half of a funder's awards for one cycle and compare release timing and negative-result reporting with the other half.","maturity":"speculative","actor":"philanthropy","cost":"small","horizonYears":2},{"id":"idea-tr2-replication-set-aside","kind":"idea","name":"Funders set aside a fixed share of budget for independent replication","aka":[],"tldr":"Almost no research money goes to checking whether published cancer findings hold up: one replication project could complete only 23 of 50 planned experiments. Requiring 3 to 5% of every funder's research budget to go to independent replication, published whatever the result, would build the missing feedback loop.","summary":"The Reproducibility Project: Cancer Biology attempted to replicate 50 high-impact papers and could complete only 23 experiments, with effect sizes on average 85% smaller than the originals. No funder has a standing replication budget. A rule that 3 to 5% of a funder's research budget goes to independent replication of findings selected by their translational importance, with results published regardless of direction, would create the missing feedback loop.","asOf":"2026-09-08","links":[{"label":"Reproducibility Project: Cancer Biology","url":"https://www.cos.io/rpcb"}],"tags":[],"related":["cruk","nci","idea-tr2-replication-before-ind"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-reproducibility","b-funding-allocation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Findings that pass funded replication will progress to clinical trials at a higher rate and fail in early clinical development less often than unreplicated findings, justifying the set-aside within five years.","rationale":"Replication is a public good that no individual lab is rewarded for producing; only funders can pay for it systematically.","test":"One large funder adopts the set-aside; track replication outcomes and downstream translational success against a matched unreplicated set.","maturity":"early-clinical","actor":"philanthropy","cost":"large","horizonYears":3},{"id":"idea-gd2-car-t-frontline-consolidation","kind":"idea","name":"GD2 CAR-T as consolidation in high-risk neuroblastoma","aka":[],"tldr":"Give engineered GD2 T cells to children in remission after standard therapy, where the long-term data show the deepest and longest cures.","summary":"This idea would give GD2-directed CAR-T cells to children with high-risk neuroblastoma who are in remission after induction, surgery and transplant, replacing or following tandem transplant and anti-GD2 antibody therapy. Long-term follow-up of the GD2-CART01 phase 1/2 trial at Bambino Gesù showed that most children infused with no evidence of disease have remained disease-free for many years, far better than expected with standard therapy. The rationale is that minimal residual disease is the ideal setting for CAR-T, that GD2 is retained after chemotherapy, and that a safety switch mitigates risk. The proposed test is a randomised phase 2/3 within COG or SIOPEN; at an early clinical stage, it addresses the bottleneck of rare and paediatric cancers and sits in the paediatric roadmap.","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT03373097: GD2-CART01 (Bambino Gesù phase 1/2)","url":"https://clinicaltrials.gov/study/NCT03373097"}],"tags":[],"related":[],"cancers":["neuroblastoma"],"sections":[],"technologies":["car-t","armored-car"],"targets":["gd2"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["gd2-cart01"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"GD2 CAR-T consolidation after induction, surgery and transplant improves 3-year EFS from ~60% to ≥75% in high-risk neuroblastoma with acceptable CRS and no chronic neuropathy.","rationale":"Minimal residual disease is the ideal CAR-T setting; GD2 is retained after chemotherapy; safety switch mitigates risk.","test":"Randomised phase 2/3 within COG or SIOPEN: standard anti-GD2 immunotherapy vs anti-GD2 followed by GD2 CAR-T; EFS primary.","maturity":"early-clinical"},{"id":"idea-moon-geriatric-assessment-default","kind":"idea","name":"Geriatric assessment by default for every older patient, and trials that admit them","aka":[],"tldr":"Most cancer patients are over 65, yet treatment is chosen by age and guesswork and trials exclude them. Assess fitness properly and design trials that include real older patients.","summary":"Geriatric assessment-guided management reduced serious toxicity without compromising survival in randomised trials (GAP70+, GAIN). Uptake remains low and trial populations are far younger and fitter than practice. The proposal is a default assessment (short validated screen with full assessment when triggered) embedded in the record for all patients over 70 starting systemic therapy, payment for the assessment, and a requirement from regulators and funders that pivotal trials include older and comorbid patients in proportion to the treated population, with pre-specified analyses.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Older and multimorbid patients are excluded and undertreated): Mohile et al., Evaluation of geriatric assessment and management on toxic effects of cancer treatment (GAP70+, Lancet 2021)","url":"https://doi.org/10.1016/S0140-6736(21)01789-X"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["geriatric-assessment"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-aging-comorbidity","b-trial-diversity"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Default assessment reduces grade 3+ toxicity in older patients by a fifth, and trial populations shift within five years to include older patients in proportion to disease incidence.","rationale":"Chronological age is a poor guide to tolerance; assessment tools are validated and quick, and trial exclusion is a habit rather than a scientific necessity.","test":"Roll out across a health system with toxicity and treatment completion as endpoints, and audit the age distribution in pivotal trials before and after the requirement.","maturity":"being-tested-at-scale","actor":"clinic","cost":"medium","horizonYears":3},{"id":"idea-acc-geriatric-assessment-by-default","kind":"idea","name":"Geriatric assessment by default for every patient over 70 starting cancer treatment","aka":[],"tldr":"A short structured check of memory, mobility, nutrition and medicines before treatment cuts serious side effects in older patients without reducing benefit. It should be automatic, not optional.","summary":"Randomised trials (GAP70+, GAIN, and others) showed that geriatric assessment with management recommendations reduces grade 3 or higher toxicity in older patients receiving chemotherapy, and ASCO guidelines recommend it. Uptake remains low because it is seen as extra work. Embedding a validated screening tool (such as G8) in intake, with automatic full assessment and management recommendations for positive screens, delivered by nurses, would make it the default.","asOf":"2026-09-08","links":[{"label":"GAP70+ trial (Mohile et al., Lancet 2021)","url":"https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01789-X/fulltext"}],"tags":[],"related":[],"cancers":[],"sections":["supportive-care"],"technologies":["geriatric-assessment"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-aging-comorbidity","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Default geriatric assessment will reduce grade 3 or higher treatment toxicity in patients over 70 by at least 20% and reduce unplanned admissions, without reducing treatment completion for curative-intent therapy.","rationale":"Level 1 evidence of benefit exists; the failure is implementation, which defaults address.","test":"A stepped-wedge implementation across 20 centres with toxicity, admissions, treatment completion, and functional decline at six months as endpoints.","maturity":"being-tested-at-scale","actor":"clinic","cost":"small","horizonYears":2},{"id":"idea-acc-geriatric-co-management-surgery","kind":"idea","name":"Geriatrician co-management for older patients having cancer surgery","aka":[],"tldr":"When a geriatrician co-manages patients over 75 around a cancer operation, as in the POSH programme at Duke and POPS in the UK, complications, delirium, length of stay and readmissions fall. Preoperative optimisation and postoperative geriatric review should be a standard part of surgical oncology pathways for this age group.","summary":"Perioperative geriatric co-management models (POSH at Duke, POPS in the UK) have shown reductions in complications, delirium, length of stay, and readmissions for older surgical patients. Cancer surgery in the over-75s is increasing and is where these gains are largest. Making co-management a standard component of surgical oncology pathways, with preoperative optimisation and postoperative geriatric review, is an organisational change with strong evidence.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Older and multimorbid patients are excluded and undertreated): Mohile et al., Evaluation of geriatric assessment and management on toxic effects of cancer treatment (GAP70+, Lancet 2021)","url":"https://doi.org/10.1016/S0140-6736(21)01789-X"}],"tags":[],"related":[],"cancers":[],"sections":["surgery"],"technologies":["geriatric-assessment"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-aging-comorbidity","b-surgery-radiation-innovation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Co-management will reduce postoperative complications and delirium by at least 25% and length of stay by two days in patients over 75 having major cancer surgery.","rationale":"The evidence base is consistent across settings; the barrier is geriatrician availability and funding, both of which can be addressed by shared roles and payment.","test":"A stepped-wedge implementation across ten surgical oncology units with complications, delirium, length of stay, readmission, and functional recovery as endpoints.","maturity":"being-tested-at-scale","actor":"clinic","cost":"medium","horizonYears":2},{"id":"idea-reg-aspirin-pik3ca-implementation","kind":"idea","name":"Get biomarker-directed aspirin after colorectal surgery into labels and guidelines","aka":[],"tldr":"A Swedish trial found that cheap aspirin roughly halved recurrence in colorectal cancer patients with a particular tumour mutation. Nobody is going to market it, so health systems must adopt it deliberately.","summary":"The ALASCCA randomised trial (reported 2025) found that low-dose aspirin for three years reduced recurrence in patients with PIK3CA-mutated colorectal cancer after surgery, following earlier observational signals, while broader trials (ASCOLT, Add-Aspirin ongoing) have shown smaller or no unselected effects. Because aspirin has no sponsor, the result risks slow and uneven adoption. The proposal is a coordinated implementation programme: guideline inclusion (ESMO, NCCN), routine PIK3CA testing at diagnosis as a reimbursed test, third-party label filings where pathways exist, and an implementation registry capturing uptake and outcomes.","asOf":"2026-09-08","links":[{"label":"ALASCCA trial, NEJM 2025","url":"https://www.nejm.org/doi/full/10.1056/NEJMoa2504650"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":[],"technologies":[],"targets":["pik3ca"],"drugs":[],"companies":[],"institutions":["karolinska","esmo"],"pathways":["pi3k-akt-mtor"],"terms":[],"trials":[],"people":[],"bottlenecks":["b-generic-repurposing","b-knowledge-diffusion"],"keyPapers":["paper-pik3ca-colorectal-lancet-oncol-2011","paper-pik3ca-colorectal-acta-oncol-2014","paper-pik3ca-colorectal-j-clin-oncol-2013"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Within three years, more than 70% of eligible PIK3CA-mutated colorectal cancer patients in participating health systems receive adjuvant aspirin, and registry data confirm a recurrence reduction consistent with the trial.","rationale":"A proven, near-free intervention that reduces recurrence in a common cancer is exactly the case where the absence of a commercial sponsor costs lives; the barrier is testing infrastructure and awareness, both of which implementation programmes address.","test":"Audit PIK3CA testing and aspirin prescribing rates in five health systems, run an implementation intervention in half of them, and compare uptake and 3-year recurrence.","maturity":"being-tested-at-scale","actor":"clinic","cost":"small","horizonYears":2},{"id":"idea-prev-lynch-aspirin-implementation","kind":"idea","name":"Get every Lynch syndrome carrier onto the right dose of aspirin","aka":[],"tldr":"Aspirin roughly halves bowel cancer in Lynch syndrome, and a dose trial is defining how little is needed. Most carriers are still not prescribed it; the task is to fix prescribing.","summary":"Aspirin roughly halves bowel cancer in Lynch syndrome, as CAPP2 showed with 600 mg, and CaPP3 is comparing 100, 300 and 600 mg, yet most carriers are still not prescribed it. This idea is an implementation programme: guideline update, an automatic recommendation at diagnosis and registry tracking of prescription and adherence, so that nearly every carrier is on the right dose within three years. The evidence exists; the gap is practice. The test is a registry-based before-and-after study with regional stepped rollout. Being tested at scale, it addresses the bottlenecks Inherited risk is mostly unidentified and Prevention we already have is not deployed, and links to aspirin for cancer prevention.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Inherited risk is mostly unidentified): Childers et al., National estimates of genetic testing in women with breast or ovarian cancer (JCO 2017)","url":"https://doi.org/10.1200/JCO.2017.73.6314"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":["prevention"],"technologies":["chemoprevention"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["msi"],"trials":[],"people":[],"bottlenecks":["b-hereditary-risk","b-prevention-adoption"],"keyPapers":["paper-childers-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Implementation raises aspirin use among Lynch carriers from under 40% to at least 80% within three years.","rationale":"The evidence exists; the gap is practice.","test":"Run a registry-based before/after study with regional stepped rollout.","maturity":"being-tested-at-scale","actor":"clinic","cost":"small","horizonYears":3},{"id":"idea-bio2-anamorelin-access","kind":"idea","name":"Get the one approved appetite drug licensed beyond a single country","aka":[],"tldr":"A drug that improves appetite and lean weight in cancer wasting is approved in Japan but almost nowhere else. Reviewing the existing evidence could widen access quickly.","summary":"Anamorelin, a ghrelin receptor agonist, is approved in Japan for cancer cachexia in several tumour types, having shown gains in lean body mass with inconsistent effects on handgrip strength in the ROMANA programme. Other regulators declined largely on the function endpoint. A reappraisal using pooled data with a qualified function endpoint, or a confirmatory pragmatic trial in a stratified population, could resolve the question.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Cachexia, toxicity and the limits of the patient): Fearon et al., Definition and classification of cancer cachexia (Lancet Oncology 2011)","url":"https://doi.org/10.1016/S1470-2045(10)70218-7"}],"tags":[],"related":[],"cancers":["nsclc","pancreatic","gastric"],"sections":[],"technologies":["exercise-oncology"],"targets":[],"drugs":[],"companies":[],"institutions":["ncc-japan"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-cachexia-supportive","b-regulatory-fragmentation","b-global-access"],"keyPapers":["paper-fearon-lancet-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A confirmatory trial in GDF-15-high or inflammation-high patients, using a qualified function endpoint and combined with exercise and protein, demonstrates a clinically meaningful functional benefit that earlier unselected trials missed.","rationale":"The lean mass effect is reproducible; what failed was the demonstration of functional translation, which is plausibly a design problem given that no anabolic stimulus was co-administered. Real-world Japanese experience provides safety and effectiveness data at scale.","test":"Publish a pooled analysis of existing trials plus Japanese real-world data; if the signal holds in stratified subgroups, run one confirmatory trial designed around the function endpoint.","maturity":"early-clinical","actor":"regulator","cost":"small","horizonYears":3},{"id":"idea-tnbc-de-escalation-for-exceptional-responders","kind":"idea","name":"Give exceptional responders less: pembrolizumab omission after complete response, anthracycline-free regimens and chemotherapy omission in lymphocyte-rich stage I disease","aka":[],"tldr":"Two thirds of women treated on the KEYNOTE-522 regimen have no tumour left at surgery and about 92 percent of them are alive without relapse at five years, yet all receive nine more cycles of pembrolizumab. Trials are now testing whether the best responders can stop early, skip the anthracycline, or in lymphocyte-rich stage I tumours skip chemotherapy altogether.","summary":"KEYNOTE-522 produced pathological complete response in 64.8 percent of patients and the CTNeoBC pooled analysis shows complete responders in triple-negative disease have an event-free survival hazard ratio of 0.24; Leon-Ferre's pooled cohort of 1,966 chemotherapy-untreated patients found five-year distant recurrence-free survival of 94 percent in stage I tumours with lymphocytes of 50 percent or more. Against this, the full regimen carries grade 3 or higher adverse events in 78 percent, permanent endocrine toxicity from pembrolizumab, and anthracycline cardiotoxicity and leukaemia risk. OptimICE-pCR (1,295 patients, primary completion May 2033) randomises complete responders to adjuvant pembrolizumab or observation; SCARLET (2,400, March 2033) tests an anthracycline-free regimen; St Gallen 2023 framed intensity and duration as the central problem. A prospective trial of chemotherapy omission in lymphocyte-rich stage I disease has not started.","asOf":"2026-09-24","links":[{"label":"Leon-Ferre et al.: tumour-infiltrating lymphocytes and outcome without chemotherapy (JAMA 2024)","url":"https://europepmc.org/article/MED/38563834"},{"label":"ClinicalTrials.gov NCT05812807","url":"https://clinicaltrials.gov/study/NCT05812807"},{"label":"ClinicalTrials.gov NCT05929768","url":"https://clinicaltrials.gov/study/NCT05929768"}],"tags":["tnbc-evidence"],"related":[],"cancers":["tnbc"],"sections":[],"technologies":["checkpoint-inhibitor","digital-pathology-ai"],"targets":[],"drugs":["pembrolizumab","doxorubicin"],"companies":[],"institutions":[],"pathways":[],"terms":["pcr","tils","de-escalation","anthracycline"],"trials":["keynote-522","optimice-pcr","scarlet-s2212"],"people":[],"bottlenecks":["b-toxicity-qol","b-dose-optimisation","b-trial-design"],"keyPapers":["paper-keynote-522-n-engl-j-med-2020","paper-keynote-522-n-engl-j-med-2024-update","paper-cortazar-ctneobc-pcr-pooled-analysis-lancet-2014","paper-leon-ferre-tils-tnbc-no-chemotherapy-jama-2024","paper-st-gallen-2023-consensus-ann-oncol-2023"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"In patients with pathological complete response after neoadjuvant chemotherapy plus pembrolizumab, omitting adjuvant pembrolizumab is non-inferior for three-year recurrence-free survival (margin 3 percentage points); in stage I tumours with stromal lymphocytes of 50 percent or more, surgery and radiotherapy without chemotherapy achieve five-year distant recurrence-free survival above 90 percent.","rationale":"Complete response and high lymphocyte infiltration each identify a group whose outcome leaves little room for a drug to improve; the toxicity, cost and time saved are certain while the benefit forgone is small and measurable.","test":"OptimICE-pCR and SCARLET readouts (2033); a single-arm or registry-embedded trial of chemotherapy omission in stage I, lymphocyte-rich disease with a pre-specified five-year distant recurrence-free survival boundary and centrally scored, digitally assisted lymphocyte counts.","maturity":"being-tested-at-scale","actor":"research","cost":"large","horizonYears":7},{"id":"idea-chronotherapy-immunotherapy","kind":"idea","name":"Give immunotherapy in the morning","aka":[],"tldr":"Several studies found patients infused with checkpoint inhibitors earlier in the day lived longer. If a randomised trial confirms it, it is a free improvement available everywhere tomorrow.","summary":"This idea proposes giving immunotherapy in the morning: patients infused with checkpoint inhibitors earlier in the day lived longer in several studies, and a randomised trial could confirm a free improvement. Retrospective cohorts (Lancet Oncology 2021 and follow-ups) and the small randomised MEMOIR signal associate morning infusions with better survival, plausibly through circadian T-cell trafficking (Circadian control pathway). The hypothesis is that infusing Immune checkpoint inhibitors against PD-1 before midday improves overall survival compared with afternoon infusions, backed by consistent cohort data and mouse immunology. The test is a large pragmatic randomised trial of morning against afternoon infusion in first-line PD-1 therapy for Non-small-cell lung cancer and Melanoma.","asOf":"2026-09-08","links":[{"label":"Qian et al., Effect of immunotherapy time-of-day infusion on overall survival in advanced melanoma (Lancet Oncology 2021)","url":"https://doi.org/10.1016/S1470-2045(21)00546-5"}],"tags":["mechanism","open-question"],"related":[],"cancers":["nsclc","melanoma"],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":["pd1"],"drugs":[],"companies":[],"institutions":["mskcc","gustave-roussy"],"pathways":["circadian-control","pd1-checkpoint"],"terms":[],"trials":["checkmate-227","checkmate-915","fianlimab-phase3-melanoma","keynote-042","relativity-098"],"people":[],"bottlenecks":[],"keyPapers":["paper-qian-lancet-oncol","paper-topalian-anti-pd1-nejm-2012","paper-pd-1-nsclc-am-j-clin-oncol-2016","paper-kras-nsclc-cancer-discov-2018"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Scheduling checkpoint-inhibitor infusions before midday improves overall survival compared with afternoon infusions, with an effect size large enough to change infusion-unit scheduling.","rationale":"Consistent direction across cohorts, mechanistic backing in mouse immunology, zero drug cost, and trivial implementation.","test":"Large pragmatic randomised trial of morning vs afternoon infusion in first-line PD-1 therapy for NSCLC and melanoma, endpoint OS; embedded immune-trafficking biomarkers.","maturity":"early-clinical"},{"id":"idea-tr2-negative-plenaries","kind":"idea","name":"Give negative trials plenary slots at the big cancer conferences","aka":[],"tldr":"Conferences headline the trials that worked, while most negative trials end up as posters or are never submitted. A standing plenary at ASCO, ESMO and AACR for negative and practice-reversing trials, with a discussant drawing lessons for design and biology, would make the failures impossible to miss.","summary":"Practice-changing negative trials (for example those that stop an established practice) are sometimes presented, but most negative trials are relegated to posters or never submitted. A standing plenary session at ASCO, ESMO and AACR for high-importance negative and reversal trials, with a discussant focused on lessons for design and biology, would raise the status of reporting failure.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Failures are hidden): Anderson et al., Compliance with results reporting at ClinicalTrials.gov (NEJM 2015)","url":"https://doi.org/10.1056/NEJMsa1409364"}],"tags":[],"related":["asco","esmo","aacr"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-negative-results","b-knowledge-diffusion"],"keyPapers":["paper-anderson-n-engl-j-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Introduction of a negative-results plenary increases submission of negative phase 3 trials to the meeting by at least 50% and their subsequent full publication rate.","rationale":"Conference prestige drives what is submitted and written up. The ASCO 'Trials in Progress' session shows that a new session type can change behaviour.","test":"Run the session at one meeting for two years; count negative-trial submissions and publications before and after.","maturity":"speculative","actor":"research","cost":"small","horizonYears":1},{"id":"idea-cost-subcutaneous-community","kind":"idea","name":"Give subcutaneous immunotherapy in community clinics and at home","aka":[],"tldr":"Under-the-skin versions of atezolizumab, nivolumab and pembrolizumab take minutes rather than an hour and need no infusion chair, so they can be given by a nurse near home, cutting facility fees and travel.","summary":"The FDA approved subcutaneous atezolizumab (2024), nivolumab (2024) and pembrolizumab (2025), each with hyaluronidase to allow a large-volume injection over a few minutes. The clinical benefit is equivalent; the economic benefit depends on where the injection is given. Delivered in a community clinic or by a home-visiting nurse, the injection avoids hospital facility fees, infusion-suite capacity and long journeys. Payment rules that require an infusion setting, and the drug's Part B status, currently blunt the saving.","asOf":"2026-09-10","links":[{"label":"FDA: Drugs@FDA approved labels","url":"https://www.accessdata.fda.gov/scripts/cder/daf/"}],"tags":[],"related":[],"cancers":[],"sections":["immunotherapy"],"technologies":["checkpoint-inhibitor"],"targets":[],"drugs":["atezolizumab","nivolumab","pembrolizumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-care-fragmentation","b-drug-pricing","b-workforce","b-global-access"],"keyPapers":["paper-checkmate-017-nejm-2015","paper-keynote-189-nejm-2018","paper-niche-2-nejm-2024"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Community or home administration of subcutaneous checkpoint inhibitors will cut per-dose administration and patient travel costs by more than half against hospital infusion, with equal safety and adherence.","rationale":"Subcutaneous trastuzumab and rituximab have been given in community settings in Europe for a decade; the barrier is payment policy, not clinical.","test":"A randomised or stepped comparison of hospital versus community administration on cost, time, patient-reported burden and adverse events.","maturity":"early-clinical","actor":"clinic","cost":"medium","horizonYears":3},{"id":"idea-rejuv-survivorship-platform-trial","kind":"idea","name":"Give survivorship interventions a shared control arm","aka":[],"tldr":"Every survivorship intervention currently raises its own small trial with its own control arm and its own endpoint. A platform trial with a shared control and a common outcome set would test several at the cost of one and a half.","summary":"The structural weakness of this literature is not that it is wrong but that it is small and fragmented. Single-centre trials of forty to a hundred people, each with its own comparator and its own questionnaire, are what a field without a sponsor produces. They are rarely large enough to change practice and almost never comparable with one another.\n\nPlatform trials solved an equivalent problem in treatment: a shared protocol, a shared control arm, prespecified rules for adding and dropping interventions, and a common endpoint set. Applied to survivorship, the obvious domains are fatigue, physical function, cognition and return to work, each with several candidate interventions and none with a dominant one. The efficiency gain comes from the shared control: a trial comparing four interventions against one control arm uses roughly half the participants of four separate two-arm trials.\n\nThis only works if the core outcome set work is done first or alongside, which is why the two proposals are linked. It also needs a funder willing to commit to a decade of infrastructure rather than a sequence of three-year grants, which is the part that has not happened.","asOf":"2026-10-02","links":[{"label":"ClinicalTrials.gov NCT04754672","url":"https://clinicaltrials.gov/study/NCT04754672"},{"label":"Courneya et al., Structured exercise after adjuvant chemotherapy for colon cancer, the CHALLENGE trial (NEJM 2025;393:13-25)","url":"https://doi.org/10.1056/NEJMoa2502760"}],"tags":["rejuvenation","survivorship","open-problem","trials"],"related":["rejuv-trial-amico","idea-rejuv-core-outcome-set-for-late-effects","idea-moon-supportive-care-arpa","rejuvenation-roadmap"],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["rejuv-agenda-no-agreed-outcome-measures","rejuv-agenda-rehabilitation-not-commissioned","b-trial-design","b-funding-allocation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A multi-arm, multi-stage platform trial with a shared control arm and a common outcome set would test survivorship interventions at a fraction of the per-intervention cost, and produce results large enough to change commissioning.","rationale":"The trials on this front are small and heterogeneous: the largest randomised trial of exercise for cancer-related cognitive impairment had 253 participants; the best long-term study of cognition after CAR-T has 40; the only sham-controlled trial of scrambler therapy was a pilot. AMICO already uses a Bayesian adaptive multi-arm multi-stage design with interim analyses to drop ineffective arms, which is the method this proposal generalises.","test":"Stand up one platform in a national trials network for a single domain, beginning with physical function after curative treatment, with three intervention arms, a shared usual-care control and a prespecified core outcome set. Judge it on cost per randomised comparison against the preceding decade of standalone trials in the same domain.","maturity":"speculative","actor":"research","cost":"large","horizonYears":8},{"id":"idea-prev-glp1-endometrial-hyperplasia","kind":"idea","name":"GLP-1 drugs to reverse endometrial precancer in women with obesity","aka":[],"tldr":"Womb precancer in women with obesity is usually treated with a hormone coil or hysterectomy. Weight-loss drugs might reverse it and protect fertility.","summary":"Womb precancer in women with obesity is usually treated with a hormone coil or hysterectomy, so this idea tests whether adding a GLP-1 receptor agonist to the levonorgestrel intrauterine system reverses atypical endometrial hyperplasia and protects fertility. Obesity drives the condition and a substantial share of cases progress to cancer; weight loss after bariatric surgery reverses hyperplasia, and GLP-1 drugs offer a non-surgical route. The aim is more complete regression and less relapse than the intrauterine system alone. The test is a 300-woman RCT with histological regression at six months as the endpoint. At early-clinical maturity it addresses the bottleneck Prevention we already have is not deployed and links to chemoprevention and endometrial cancer.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Prevention we already have is not deployed): Islami et al., Proportion of cancer attributable to modifiable risk factors (CA 2018)","url":"https://doi.org/10.3322/caac.21440"}],"tags":[],"related":[],"cancers":["endometrial"],"sections":["prevention"],"technologies":["chemoprevention"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption"],"keyPapers":["paper-islami-ca-cancer-j-clin"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Adding a GLP-1 receptor agonist increases complete regression from about 70% to at least 85% and halves relapse at two years.","rationale":"Weight loss after bariatric surgery reverses hyperplasia; GLP-1 offers a non-surgical route.","test":"300-woman RCT.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":3},{"id":"idea-nl-glp1-adjuvant-hr-breast","kind":"idea","name":"GLP-1 receptor agonists as adjuvant weight-loss therapy in HR-positive breast cancer","aka":[],"tldr":"Coaching-based weight loss did not clearly cut breast cancer recurrence in BWEL, perhaps because the weight loss was too small. Drugs that produce three times as much weight loss could settle whether weight itself matters.","summary":"BWEL achieved modest weight loss with no clear iDFS effect. Bariatric surgery cohorts, with 25-30% weight loss, show large reductions in hormone-related cancers. GLP-1 receptor agonists sit between the two and are already widely used by breast cancer survivors off-trial; a randomised trial would answer the biological question BWEL could not and define safety alongside endocrine therapy (lean mass loss, bone density, gastrointestinal effects with CDK4/6 inhibitors).","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Survivorship and late effects are neglected): NCI Office of Cancer Survivorship statistics","url":"https://cancercontrol.cancer.gov/ocs/statistics"}],"tags":[],"related":["idea-prev-glp1-cancer-prevention-rct"],"cancers":["breast-hr-positive"],"sections":["nutrition-lifestyle","hormonal"],"technologies":["glp1-agonists-cancer-risk","dietitian-led-weight-loss-breast","endocrine-therapy","resistance-training-cachexia"],"targets":[],"drugs":["letrozole","abemaciclib"],"companies":["eli-lilly"],"institutions":[],"pathways":[],"terms":["obesity-related-cancers","energy-balance","body-composition"],"trials":["bwel"],"people":[],"bottlenecks":["b-survivorship","b-funding-allocation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"In women with stage II-III HR-positive breast cancer and BMI at least 30 on adjuvant endocrine therapy, two years of semaglutide or tirzepatide with resistance exercise improves invasive disease-free survival compared with lifestyle counselling alone, with the effect mediated by weight loss and reduced insulin and oestradiol.","rationale":"Obesity is associated with about 30% higher breast cancer mortality and with reduced aromatase inhibitor efficacy; GLP-1 receptor agonists produce sustained 15-20% weight loss; observational data suggest lower obesity-related cancer incidence. The exercise component protects lean mass, which rapid weight loss otherwise depletes.","test":"Phase 3 placebo-controlled trial (about 3,000 women) with iDFS primary endpoint, body composition by DXA, bone density and patient-reported outcomes; pre-specified mediation analysis by percentage weight loss. An industry-academic partnership is realistic given the commercial value of a cancer label.","maturity":"speculative","actor":"industry","cost":"large","horizonYears":8},{"id":"idea-prev-cgm-glycaemic-drift-pancreas","kind":"idea","name":"Glucose monitor data as an early pancreatic cancer signal","aka":[],"tldr":"Millions now wear continuous glucose monitors. A sudden, unexplained worsening of glucose control in a middle-aged wearer could be flagged as a possible early sign of pancreatic cancer.","summary":"Pancreatic cancer causes new or worsening diabetes one to three years before diagnosis. Continuous glucose monitor streams give a far finer signal of glycaemic drift than sporadic HbA1c. Propose a retrospective study linking CGM data to pancreatic cancer outcomes to define a drift signature, then a prospective alert routing flagged users to ENDPAC-style work-up.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The hardest cancers are found late): Crosby et al., Early detection of cancer (Science 2022)","url":"https://doi.org/10.1126/science.aay9040"}],"tags":[],"related":[],"cancers":["pancreatic"],"sections":["early-detection"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-early-detection"],"keyPapers":["paper-crosby-science"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A CGM-derived glycaemic drift signature identifies incident pancreatic cancer with a positive predictive value of at least 2% in wearers over 50, enough to justify imaging.","rationale":"The biology is established; the sensor data is new and continuous; the population is large and, on many platforms, already consented for research use.","test":"Start with retrospective linkage in a large CGM database with cancer registry outcomes (small cost); then run a prospective alert pilot.","maturity":"speculative","actor":"data","cost":"small","horizonYears":4},{"id":"idea-prev-traceback-deceased-probands","kind":"idea","name":"Go back to families of women who died of ovarian cancer and offer BRCA testing","aka":[],"tldr":"Women who died of ovarian cancer without ever having BRCA testing leave relatives who are otherwise unreachable. Retesting archived tumour tissue and contacting families, piloted on 2,000 cases from the past 15 years, would find carriers before they develop cancer; US pilots show it is feasible and ethically acceptable.","summary":"Women who died of ovarian cancer without BRCA testing leave carriers in their families undetected, so this idea retests their archived tumour tissue and contacts relatives, scaling traceback to ovarian, young-onset breast and pancreatic cancer cases from the past 15 years. US pilots show feasibility and ethical acceptability, BRCA is common in ovarian cancer, and relatives of deceased probands are otherwise unreachable. The aim is to find previously unknown carriers before they develop cancer. The test is a regional traceback pilot on 2,000 archived cases. At early-clinical maturity it addresses the bottleneck Inherited risk is mostly unidentified and links to germline testing and BRCA.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Inherited risk is mostly unidentified): Childers et al., National estimates of genetic testing in women with breast or ovarian cancer (JCO 2017)","url":"https://doi.org/10.1200/JCO.2017.73.6314"}],"tags":[],"related":[],"cancers":["ovarian"],"sections":["prevention"],"technologies":["germline-testing"],"targets":["brca"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-hereditary-risk"],"keyPapers":["paper-childers-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Traceback identifies at least one previously unknown carrier per ten deceased probands tested.","rationale":"BRCA prevalence in ovarian cancer is about 15%, and relatives of deceased probands are otherwise unreachable.","test":"Run a regional traceback pilot on 2,000 archived cases.","maturity":"early-clinical","actor":"clinic","cost":"medium","horizonYears":3},{"id":"idea-data-gcp-for-real-world-data","kind":"idea","name":"Good practice standards and inspection for real-world data sources","aka":[],"tldr":"Trials are inspected to check the data are real and traceable. Do the same for the hospital databases used to make regulatory decisions.","summary":"Clinical trial data are governed by Good Clinical Practice and inspected; real-world data sources used in regulatory submissions are not. The proposal is a 'GCP for real-world data': standards for provenance, traceability to source records, curation documentation, fitness-for-purpose assessment and inspection rights, with accreditation of data sources. The FDA's RWE framework and EMA's DARWIN EU data quality framework are starting points.","asOf":"2026-09-08","links":[{"label":"EMA DARWIN EU","url":"https://www.darwin-eu.org/"},{"label":"FDA Real-World Evidence framework","url":"https://www.fda.gov/science-research/science-and-research-special-topics/real-world-evidence"}],"tags":[],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["real-world-evidence"],"trials":[],"people":[],"bottlenecks":["b-real-world-evidence","b-regulatory-fragmentation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Accredited data sources will produce RWE that regulators accept as supportive evidence in a substantially higher share of submissions, and audit will reveal material provenance errors in a minority of current sources.","rationale":"Regulators discount RWE partly because they cannot verify it; accreditation with inspection is how the same problem was solved for trials and for laboratories (CLIA, ISO 15189).","test":"Pilot accreditation with five data sources (two commercial, two academic, one registry); publish audit findings and regulator uptake of RWE from accredited versus non-accredited sources over two years.","maturity":"early-clinical","actor":"regulator","cost":"medium","horizonYears":3},{"id":"idea-fund-phase-two-failure-reinsurance","kind":"idea","name":"Government reinsurance for phase 2 failures of first-in-class cancer drugs","aka":[],"tldr":"Investors avoid genuinely new cancer drugs because most fail in mid-stage trials. A public insurance scheme would repay part of the loss when a first-in-class drug fails honestly, making the bet worth taking.","summary":"A publicly-backed reinsurance pool that pays a fraction (for example 40%) of documented phase 2 trial costs back to sponsors of qualifying first-in-class oncology programmes when the trial fails on pre-registered efficacy criteria, with a premium paid by participants and conditions on data disclosure (the failure must be published with full data within twelve months). This directly lowers the risk premium that steers capital toward follow-on assets, and produces a public record of negative results as a by-product. Export credit agencies and crop insurance are analogous risk-sharing designs; the biotech-specific precedent is milestone-based grant funding by CPRIT and BARDA.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Incentives reward me-too drugs and marginal gains): Upadhaya et al., PD1/PDL1 inhibitor clinical trial landscape (Nat Rev Drug Discov 2022)","url":"https://doi.org/10.1038/d41573-022-00030-4"}],"tags":[],"related":["idea-fund-sovereign-first-in-class-coinvestment","idea-fund-trial-data-trust","idea-fund-first-in-class-prize"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["cprit"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-incentive-misalignment","b-translational-valley"],"keyPapers":["paper-upadhaya-nat-rev-drug-discov"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A phase 2 reinsurance pool increases the share of oncology phase 2 starts that are first-in-class by at least a quarter among participating sponsors within five years, at a net public cost per additional novel programme below the equivalent grant subsidy.","rationale":"Venture and pharma portfolio managers explicitly price the higher attrition of novel mechanisms; insuring the downside is a cheaper way to change the expected value than subsidising the upside, and it conditions payment on transparency, which addresses hidden failures.","test":"Capitalise a pilot pool for a defined cohort of first-in-class programmes, pre-register the counterfactual using historical pipeline composition, and evaluate pipeline shift and disclosure compliance after five years.","maturity":"speculative","actor":"policy","cost":"large","horizonYears":5},{"id":"idea-reg-tiered-pricing-for-exclusivity","kind":"idea","name":"Grant extra exclusivity only in exchange for binding low prices in poorer countries","aka":[],"tldr":"Companies get longer monopolies for rare and paediatric cancer drugs. That reward should come with a commitment to sell at cost in low-income countries.","summary":"Orphan, paediatric and data exclusivity extensions are valuable regulatory rewards granted without access conditions. The proposal is that regulators condition these extensions on a registered commitment: tiered pricing at or near cost in all low- and lower-middle-income countries, filing for registration in those countries within a year of first approval, and participation in pooled procurement. Non-compliance would shorten the exclusivity. Similar conditionality is used in some public research funding agreements and in the EU's 2023 pharmaceutical reform proposals linking exclusivity to launch in all member states.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Prices and value): Prasad, De Jesús & Mailankody, The high price of anticancer drugs: origins, implications, barriers, solutions (Nat Rev Clin Oncol 2017)","url":"https://doi.org/10.1038/nrclinonc.2017.31"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-drug-pricing","b-global-access"],"keyPapers":["paper-prasad-nat-rev-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Conditional exclusivity increases the proportion of new oncology drugs registered and available at tiered prices in low-income countries within two years of first approval from a small minority to a majority, without reducing the number of orphan and paediatric oncology programmes.","rationale":"Exclusivity is a public grant; attaching access conditions costs high-income payers nothing and gives companies a clear, predictable requirement rather than ad hoc pressure.","test":"Model the revenue impact for recent orphan oncology approvals; implement the condition in one major jurisdiction and track LMIC registration and pricing over five years.","maturity":"speculative","actor":"regulator","cost":"small","horizonYears":5},{"id":"idea-tr2-null-result-reporting","kind":"idea","name":"Grant progress reports must list what did not work","aka":[],"tldr":"Researchers report their successes to funders every year. Make them report their failures too, in a structured, searchable way.","summary":"Annual progress reports to funders describe positive findings. A mandatory structured field for hypotheses tested and not supported, with model system and readout, shared across funders and made searchable (with an embargo if requested), would create a negative-results database as a by-product of existing paperwork.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Failures are hidden): Anderson et al., Compliance with results reporting at ClinicalTrials.gov (NEJM 2015)","url":"https://doi.org/10.1056/NEJMsa1409364"}],"tags":[],"related":["nci","cruk","idea-tr2-preclinical-negative-registry"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-negative-results"],"keyPapers":["paper-anderson-n-engl-j-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Within two years the database contains at least 5,000 structured null results from oncology grants and is queried by researchers designing new experiments, as shown by usage logs and surveys.","rationale":"Reporting to funders is already compulsory, so the marginal effort is small. Funders have the leverage that journals lack.","test":"Add the field at one large funder; measure completion quality and downstream use after eighteen months.","maturity":"speculative","actor":"policy","cost":"small","horizonYears":1},{"id":"idea-bio2-mechanism-defined-baskets","kind":"idea","name":"Group trials by broken mechanism, not by organ or single mutation","aka":[],"tldr":"Rare cancers often share a broken cellular machine even when they arise in different organs. Grouping patients by that shared fault makes trials possible.","summary":"Tumour-agnostic approvals so far follow single alterations such as NTRK fusions or mismatch repair deficiency. Many rare cancers instead share mechanism classes (SWI/SNF complex loss including SMARCB1 and SMARCA4, chromatin regulator loss, fusion-driven transcription factor addiction, metabolic enzyme mutations) that could define baskets with dozens of contributing diagnoses and a common therapeutic hypothesis such as EZH2 or PRMT5 dependence.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Rare and paediatric cancers without markets): Gatta et al., Rare cancers are not so rare: the rare cancer burden in Europe (EJC 2011)","url":"https://doi.org/10.1016/j.ejca.2011.08.008"}],"tags":[],"related":["idea-mtap-prmt5-mesothelioma","depmap","oncokb"],"cancers":["sarcoma","ovarian"],"sections":[],"technologies":["synthetic-lethality-approaches","crispr-screens","epigenetic-drugs"],"targets":["ezh2","idh","kmt2a"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["synthetic-lethality","tumour-agnostic","gene-fusion"],"trials":["pediatric-match","nct03213665"],"people":[],"bottlenecks":["b-rare-cancers","b-tumor-heterogeneity","b-trial-design"],"keyPapers":["paper-gatta-eur-j-cancer","paper-ezh2-ovarian-mol-cancer-ther-2018","paper-ezh2-sarcoma-bmc-med-2011","paper-ezh2-sarcoma-biochem-pharmacol-2023"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Mechanism-class baskets, for example SWI/SNF-deficient tumours treated with an EZH2 inhibitor, show consistent response across contributing histologies, justifying mechanism-level rather than mutation-level approvals.","rationale":"Tazemetostat activity in SMARCB1-deficient epithelioid sarcoma is proof that a chromatin mechanism class can be targeted, and synthetic lethal relationships in this space are well mapped in cell line dependency data. Mechanism classes are far more prevalent than any single alteration.","test":"A basket trial enrolling by mechanism class with pre-specified histology-level Bayesian borrowing; kill the class hypothesis if response is confined to one histology.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":6},{"id":"idea-bio2-ctc-culture-functional-testing","kind":"idea","name":"Grow blood-borne tumour cells to test drugs on the cells that actually spread","aka":[],"tldr":"Drug tests normally use cells from the original tumour. Growing the rarer cells found in blood would test drugs against the cells that are actually travelling.","summary":"Cultures and xenografts derived from circulating tumour cells have been established in small-cell lung, breast and prostate cancer, with success rates that rise with CTC burden. They capture the metastasis-competent population and can be sampled repeatedly without a biopsy. Scaling the protocols, publishing failure rates honestly, and linking drug sensitivity to subsequent clinical course would create the first functional assay of metastatic competence.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Metastasis is understood least and studied last): Dillekås et al., Are 90% of deaths from cancer caused by metastases? (Cancer Medicine 2019)","url":"https://doi.org/10.1002/cam4.2474"}],"tags":[],"related":[],"cancers":["sclc","prostate"],"sections":[],"technologies":["liquid-biopsy","functional-drug-testing","organoids","pdx-models"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["caroline-dive","fiona-blackhall"],"bottlenecks":["b-metastasis-biology","b-preclinical-models"],"keyPapers":["paper-dillekas-cancer-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Ex vivo models can be established from circulating tumour cells in over 40% of patients with high CTC burden, and their drug sensitivity predicts subsequent clinical response better than sequencing of the archival primary.","rationale":"CTC-derived explant models in small-cell lung cancer reproduce patient chemosensitivity and molecular subtype, and are the field's best worked example. Serial sampling makes resistance trackable in a way tissue biopsy cannot.","test":"Multi-centre protocol harmonisation study in small-cell lung and prostate cancer, reporting establishment rate, time to model and concordance of ex vivo sensitivity with clinical response in 100 patients.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":7},{"id":"idea-tr2-organoid-coclinical-arms","kind":"idea","name":"Grow each trial patient's tumour as organoids to decide which platform arm opens next","aka":[],"tldr":"While patients are treated in a platform trial, their tumour cells grow in a dish and are tested against dozens of drug pairs. The pairs that win in the dish become the next arms.","summary":"Co-clinical organoid programmes (for example in pancreatic and colorectal cancer) have tested whether dish responses predict patient responses. The proposal inverts the use: a platform trial's organoid bank becomes a combination discovery engine, testing hundreds of pairs on the same tumours that are being treated, so the next arm is chosen from data on the trial population itself rather than on generic cell lines.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Too many combinations to test): Palmer & Sorger, Combination cancer therapy can confer benefit via patient-to-patient variability without drug additivity or synergy (Cell 2017)","url":"https://doi.org/10.1016/j.cell.2017.11.009"}],"tags":[],"related":["pdac-organoid-pharmacotyping","xilis","curesponse","sengine","idea-organoid-guided-adc"],"cancers":["pancreatic","colorectal"],"sections":[],"technologies":["organoids","functional-drug-testing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-combination-space","b-preclinical-models"],"keyPapers":["paper-palmer-cell"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Arms nominated by co-clinical organoid screening achieve a higher objective response rate than arms nominated by investigator choice in the same platform, with the difference visible after two rounds of arm selection.","rationale":"Organoid sensitivity correlates with patient response for cytotoxics and some targeted agents. Pairs tested on the actual trial population avoid the mismatch between cell-line panels and the patients enrolled.","test":"Add a co-clinical organoid screen to an existing pancreatic or colorectal platform; nominate two arms by organoid data and two by steering committee; compare response rates after 40 patients per arm.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":4},{"id":"idea-bio2-tertiary-lymphoid-induction","kind":"idea","name":"Grow immune command posts inside tumours","aka":[],"tldr":"Tumours that contain small immune structures resembling lymph nodes respond far better to immunotherapy. Inducing those structures on purpose could make cold tumours responsive.","summary":"Tertiary lymphoid structures and B-cell aggregates are among the strongest predictors of checkpoint response in sarcoma, melanoma and renal cancer. Their formation depends on LIGHT, lymphotoxin, CXCL13 and stromal organiser cells, and vascular-targeted LIGHT fusions induced them in mouse tumours. No clinical programme currently has tertiary lymphoid structure induction as its declared primary mechanism.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Cold tumours and the immunosuppressive microenvironment): Haslam & Prasad, Estimation of the percentage of US patients eligible for and responding to checkpoint inhibitors (JAMA Netw Open 2019)","url":"https://doi.org/10.1001/jamanetworkopen.2019.2535"}],"tags":[],"related":[],"cancers":["sarcoma","rcc","melanoma"],"sections":[],"technologies":["single-cell-spatial","checkpoint-inhibitor","cytokine-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["tils","cold-vs-hot"],"trials":[],"people":["jean-yves-blay"],"bottlenecks":["b-tme-immunosuppression","b-immunotherapy-response"],"keyPapers":["paper-haslam-jama-netw-open"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"An induction regimen based on LIGHT or CXCL13 delivery generates measurable tertiary lymphoid structures in serial biopsies of cold tumours, and their appearance is accompanied by intratumoural clonal T-cell expansion.","rationale":"The association between these structures and response is unusually strong and reproducible across tumour types and datasets, and murine induction is achievable. Sarcoma trials already stratify by a B-cell-rich immune class, providing a ready-made target population.","test":"Phase 1 with mandatory serial biopsies in immune-class-defined sarcoma or renal cancer, primary endpoint the histological appearance of new lymphoid structures, secondary endpoint T-cell clonal expansion.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":8},{"id":"idea-bio1-ctc-derived-explants","kind":"idea","name":"Grow models from tumour cells in the blood when a biopsy is impossible","aka":[],"tldr":"Some patients cannot have their tumour biopsied safely. Cancer cells captured from a blood sample can sometimes be grown into a model instead.","summary":"Circulating tumour cell-derived explants have been established in small cell lung cancer and reflect donor genomics and chemotherapy response, and CTC-derived organoids have been reported in prostate and breast cancer. Success rates depend on CTC counts, which are highest in exactly the aggressive diseases where biopsies are hardest. Scaling requires better capture, culture media and cryopreservation.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Lab models that fail to predict what happens in patients): Wong, Siah & Lo, Estimation of clinical trial success rates (Biostatistics 2019)","url":"https://doi.org/10.1093/biostatistics/kxx069"}],"tags":[],"related":[],"cancers":["sclc","prostate"],"sections":[],"technologies":["liquid-biopsy","organoids","pdx-models"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-preclinical-models","b-resistance"],"keyPapers":["paper-wong-biostatistics"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"CTC-derived models can be established from a meaningful fraction of patients with high CTC counts and reproduce the donor's response to platinum chemotherapy in the majority of matched cases.","rationale":"Serial blood sampling permits models from multiple timepoints, including at resistance, which tissue biopsy programmes rarely achieve; small cell lung cancer explants have already demonstrated this.","test":"Attempt derivation from 100 patients with high CTC burden across SCLC, prostate and breast cancer; report establishment rate, genomic fidelity and chemotherapy response concordance.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":4},{"id":"idea-bio1-organoid-immune-coculture","kind":"idea","name":"Grow tumour organoids together with the patient's own immune cells","aka":[],"tldr":"Lab-grown mini-tumours usually contain only cancer cells. Adding the patient's own immune cells lets researchers test immunotherapy outside the body.","summary":"Air-liquid interface organoids and reconstituted co-cultures preserve or restore tumour-infiltrating lymphocytes and myeloid cells, and have been used to model checkpoint blockade responses and to expand tumour-reactive T cells. Standardising these systems, including autologous peripheral blood mononuclear cell co-cultures with defined killing readouts, would give an ex vivo assay for immunotherapy and cell therapy that plain organoids cannot provide.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Lab models that fail to predict what happens in patients): Wong, Siah & Lo, Estimation of clinical trial success rates (Biostatistics 2019)","url":"https://doi.org/10.1093/biostatistics/kxx069"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["organoids","functional-drug-testing","til-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":["nki"],"pathways":[],"terms":["tils","cold-vs-hot"],"trials":[],"people":[],"bottlenecks":["b-preclinical-models","b-immunotherapy-response"],"keyPapers":["paper-wong-biostatistics"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A standardised organoid-immune co-culture killing assay discriminates checkpoint inhibitor responders from non-responders in a prospective cohort with accuracy better than PD-L1 immunohistochemistry.","rationale":"Immunotherapy prediction is the field's most valuable unmet biomarker problem and functional assays outperform expression markers in other settings, such as ex vivo drug sensitivity in leukaemia.","test":"Assay 150 pre-treatment samples from patients starting checkpoint therapy with blinded scoring; compare accuracy with PD-L1 and tumour mutational burden.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":4},{"id":"idea-acc-childhood-medicines-platform-scale","kind":"idea","name":"Guaranteed-quality childhood cancer medicines free of charge in 50 countries","aka":[],"tldr":"Most children with cancer in rich countries are cured; most in poor countries are not, often because cheap drugs are missing. A global platform now ships quality drugs free; scaling it to 50 countries would be one of the highest-value cancer interventions available.","summary":"The WHO and St. Jude Global Platform for Access to Childhood Cancer Medicines began deliveries in 2025 to a first set of countries, providing an uninterrupted supply of quality-assured medicines at no cost. Childhood cancers are highly curable with generic drugs, so the return per dollar is very high. The proposal is to commit the funding and logistics to reach 50 countries and to measure survival, not deliveries, as the outcome.","asOf":"2026-09-08","links":[{"label":"St. Jude Global","url":"https://www.stjude.org/global"}],"tags":[],"related":[],"cancers":["all-leukemia","hodgkin-lymphoma","neuroblastoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-global-access","b-rare-cancers"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Countries receiving platform medicines will show a measurable rise in two-year survival for acute lymphoblastic leukaemia and Hodgkin lymphoma within four years of first delivery, compared with pre-platform baselines from hospital registries.","rationale":"The drugs are cheap, off-patent, and the protocols are standard; the gap is supply reliability and quality assurance, both of which a platform can fix at scale.","test":"Prospective survival tracking in platform hospitals using the SIOP-style hospital-based registries, with abandonment and toxic-death rates as secondary endpoints.","maturity":"being-tested-at-scale","actor":"philanthropy","cost":"large","horizonYears":5},{"id":"idea-tr1-open-trials-inside-guidelines","kind":"idea","name":"Guidelines list the open trials at every decision point, updated monthly","aka":[],"tldr":"Treatment guidelines tell doctors what to do at each step but rarely which trials are open for that step. Adding a live, monthly-updated list to each decision node would put trials where doctors look.","summary":"NCCN, ESMO and national guidelines add a machine-updated 'open trials for this node' panel to each algorithm step, generated from registry data filtered by setting and line of therapy, with a link to slot availability. The static 'clinical trial participation is encouraged' footnote becomes actionable.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Trials enrol too few, too slowly): Unger et al., Systematic review of barriers to cancer trial participation (JNCI 2019)","url":"https://doi.org/10.1093/jnci/djy221"}],"tags":[],"related":["nccn","esmo-guidelines","clinicaltrials-gov"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["esmo"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-enrolment","b-knowledge-diffusion"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Decision nodes with trial panels will have higher referral rates to the listed trials than nodes without, measured via referral-source tracking at trial sites.","rationale":"Guidelines are the most consulted documents in oncology practice; embedding trials there reaches every clinician without new software.","test":"One guideline body pilots panels for two cancers; sites of listed trials record referral source for a year.","maturity":"speculative","actor":"research","cost":"small","horizonYears":1},{"id":"idea-reg-hospital-exemption-harmonised","kind":"idea","name":"Harmonise Europe's hospital exemption for academic cell therapies, with one registry","aka":[],"tldr":"Spain lets hospitals make and use their own CAR-T under a special rule; most European countries do not. A common rule with shared outcome tracking would spread affordable academic products.","summary":"The EU ATMP Regulation's hospital exemption is implemented differently in each member state: Spain has authorised academic CAR-T products (ARI-0001, ARI-0002h) at far lower cost than commercial products, while other countries apply the exemption so narrowly that academic products cannot be used routinely. The 2023 EU pharmaceutical reform proposals address this partly. The proposal is a harmonised hospital exemption with common GMP and pharmacovigilance requirements, mandatory participation in a European outcomes registry, and cross-border recognition so an exempted product from one member state can be used in another.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Manufacturing cost and time for living and radioactive medicines): Hernandez, Prasad & Gellad, Total costs of chimeric antigen receptor T-cell immunotherapy (JAMA Oncology 2018)","url":"https://doi.org/10.1001/jamaoncol.2018.0977"}],"tags":[],"related":[],"cancers":["all-leukemia","multiple-myeloma"],"sections":[],"technologies":["car-t"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-manufacturing-cell-therapy","b-regulatory-fragmentation"],"keyPapers":["paper-hernandez-jama-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Harmonisation increases the number of European patients treated with academic CAR-T tenfold within five years, with 12-month outcomes within the range of commercial products in the same registry.","rationale":"Academic CAR-T has published outcomes comparable to commercial products in matched populations at a third of the price; the barrier is legal fragmentation, not quality.","test":"Compare registry outcomes for academic and commercial CAR-T in Spain; model the access gain from harmonisation; pilot cross-border use between two member states under a bilateral agreement.","maturity":"early-clinical","actor":"policy","cost":"small","horizonYears":4},{"id":"idea-tnbc-pd-l1-assay-harmonisation","kind":"idea","name":"Harmonise PD-L1 testing for triple-negative breast cancer around one scored assay, with external quality assurance","aka":[],"tldr":"Three PD-L1 tests run on the same tumours called 46, 75 and 73 percent of them positive and agreed only 69 percent of the time. With atezolizumab withdrawn, pembrolizumab's test (22C3, combined positive score of 10) is the only one that matters, yet laboratories still run whichever kit they have. One assay, one score and a proficiency scheme would end answers that vary by postcode.","summary":"Rugo's IMpassion130 analysis of 614 tumours found PD-L1 immune cell positivity of 46.4 percent by SP142, 74.9 by SP263 and 73.1 by 22C3, concordance of 69 percent, and harmonised cut-offs reaching only about 75 percent; atezolizumab's benefit lay in the tumours all three called positive. KEYNOTE-355 selected on 22C3 combined positive score of 10 or more, which the ASCO 2022 biomarker guideline made the recommended test, and the atezolizumab indication was withdrawn in the United States in 2021. Practice has not caught up: SP142 remains in use where atezolizumab was adopted, laboratories score immune cells and combined positive score interchangeably, and scoring of the combined positive score at the 10 threshold has known inter-observer variation. Digital scoring and external quality assurance schemes exist for HER2 and could be extended.","asOf":"2026-09-24","links":[{"label":"Rugo et al.: PD-L1 assay comparison in IMpassion130 (J Natl Cancer Inst 2021)","url":"https://europepmc.org/article/MED/34097070"}],"tags":["tnbc-evidence"],"related":[],"cancers":["tnbc"],"sections":[],"technologies":["digital-pathology-ai","checkpoint-inhibitor"],"targets":["pdl1"],"drugs":["pembrolizumab","ventana-pd-l1-sp142"],"companies":[],"institutions":["nice","asco"],"pathways":[],"terms":["cps","ihc"],"trials":["keynote-355","impassion130","impassion131"],"people":[],"bottlenecks":["b-biomarker-validation","b-regulatory-fragmentation","b-knowledge-diffusion"],"keyPapers":["paper-rugo-pd-l1-assay-comparison-impassion130-jnci-2021","paper-asco-biomarkers-metastatic-breast-cancer-guideline-jco-2022","paper-keynote-355-nejm-2022"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Mandating 22C3 combined positive score (or a validated equivalent with demonstrated concordance above 90 percent at the 10 threshold) with participation in an external quality assurance scheme will reduce discordant PD-L1 calls between laboratories to under 10 percent and increase the proportion of eligible patients receiving first-line pembrolizumab.","rationale":"The test decides access to a survival-prolonging drug and the evidence that assays are not interchangeable is direct; harmonisation costs little because the assay already exists and quality assurance infrastructure exists for other breast biomarkers.","test":"Ring study of 22C3 combined positive score across national laboratories with a reference panel; before-and-after audit of assay use, discordance rate and pembrolizumab uptake after a national harmonisation directive; a digital scoring validation against the reference panel.","maturity":"early-clinical","actor":"regulator","cost":"small","horizonYears":3},{"id":"idea-bispecific-vs-car-t-second-line","kind":"idea","name":"Head-to-head bispecific vs CAR-T in second-line LBCL","aka":[],"tldr":"Nobody has directly compared an off-the-shelf bispecific with CAR-T in the same patients; a trial would settle where each belongs.","summary":"The idea is a head-to-head randomised trial of an off-the-shelf CD20 bispecific, epcoritamab or glofitamab with chemotherapy, against the CAR-T product axicabtagene ciloleucel in second-line large B-cell lymphoma. CAR-T has phase 3 event-free and overall survival wins in early relapse, while bispecifics have single-arm data and one mixed phase 3 in EPCORE DLBCL-1, but can be repeated, arrive within a week, and win on access and cost. The hypothesis is that a bispecific with chemotherapy is non-inferior to axi-cel on event-free survival at lower cost with comparable cytokine release syndrome. The test is a randomised non-inferiority trial with quality of life and cost as secondary endpoints; the speculative idea addresses the manufacturing bottleneck.","asOf":"2026-09-07","links":[{"label":"ZUMA-7: axi-cel CAR-T instead of salvage chemotherapy and transplant for large B-cell lymphoma that relapses early (New England Journal of Medicine 2022)","url":"https://doi.org/10.1056/NEJMoa2116133"},{"label":"ZUMA-1: axicabtagene ciloleucel for refractory large B-cell lymphoma, the first CAR-T approved for lymphoma (New England Journal of Medicine 2017)","url":"https://doi.org/10.1056/NEJMoa1707447"}],"tags":[],"related":[],"cancers":["dlbcl"],"sections":[],"technologies":["t-cell-engager","car-t"],"targets":[],"drugs":["epcoritamab","glofitamab","axicabtagene-ciloleucel"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-zuma-1-axi-cel-nejm-2017","paper-glofitamab-dlbcl-n-engl-j-med-2022","paper-glofitamab-dlbcl-lancet-2024"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Epcoritamab or glofitamab with chemotherapy is non-inferior to axi-cel on EFS in second-line LBCL with a lower cost and comparable CRS.","rationale":"Both redirect T cells to CD19/CD20+ cells; bispecifics can be repeated and are available in a week.","test":"Randomised non-inferiority trial with EFS primary, quality-of-life and cost secondary; ctDNA-defined stratification.","maturity":"speculative"},{"id":"idea-pv-hepcidin-first","kind":"idea","name":"Hepcidin-based control as first-line treatment in low-risk polycythaemia vera","aka":[],"tldr":"Rusfertide replaced phlebotomy in patients who needed it often. The open question is whether hepcidin control from diagnosis, in low-risk patients who today get phlebotomy alone, prevents the iron deficiency, the count swings and perhaps the clots that phlebotomy leaves behind.","summary":"Phlebotomy has been first-line PV treatment for a century, but it makes patients iron deficient, lets the haematocrit swing between sessions and is time consuming. Rusfertide and the TMPRSS6-silencing RNA drugs in early trials hold the haematocrit steady by limiting iron to the marrow. VERIFY tested rusfertide only as an add-on in phlebotomy-dependent disease. The idea is a first-line trial in low-risk patients comparing hepcidin control with standard phlebotomy on haematocrit time-in-target, symptoms and thrombosis, with cost and injection burden weighed against the benefit.","asOf":"2026-09-16","links":[],"tags":["polycythaemia-vera","mpn"],"related":[],"cancers":["polycythaemia-vera"],"sections":[],"technologies":[],"targets":[],"drugs":["rusfertide"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["verify","low-pv"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"In newly diagnosed low-risk PV, a hepcidin mimetic will keep patients within the haematocrit target for a larger share of time than phlebotomy, with fewer symptoms of iron deficiency and no increase in thrombosis.","rationale":"Haematocrit variability, not only the average, is linked to clot risk; VERIFY showed sustained control and better patient-reported outcomes; iron deficiency symptoms are common and under-recognised in phlebotomised patients.","test":"A randomised trial of about 300 low-risk patients, hepcidin mimetic versus phlebotomy plus aspirin, with time within haematocrit target over two years as the primary endpoint and thrombosis, fatigue scores and cost per patient-year as secondary endpoints.","maturity":"being-tested-at-scale","actor":"industry","cost":"medium","horizonYears":5},{"id":"idea-her2-adc-serous-endometrial","kind":"idea","name":"HER2 ADCs as standard for HER2-positive serous endometrial cancer","aka":[],"tldr":"Serous endometrial cancers often overproduce HER2. Enhertu already works in them; testing HER2 in every p53-abnormal tumour and using the ADC earlier could change outcomes for the worst subtype.","summary":"Serous endometrial carcinomas, which fall in the p53-abnormal molecular class, frequently amplify HER2, and this idea proposes testing HER2 in every p53-abnormal tumour and using trastuzumab deruxtecan earlier. T-DXd produced a high response rate in HER2 IHC 3+ endometrial cancer in DESTINY-PanTumor02, leading to tumour-agnostic approval, and trastuzumab with chemotherapy improved progression-free survival in a randomised phase 2 reported by Fader in 2018. The rationale is strong single-agent activity, a defined biomarker, and a subtype with the shortest survival that gains least from immunotherapy. The proposed test is a randomised phase 3 of first-line chemo-immunotherapy with or without T-DXd in HER2-positive p53abn disease, at an early clinical stage; NRG-GY026 tests trastuzumab.","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT04482309: DESTINY-PanTumor02","url":"https://clinicaltrials.gov/study/NCT04482309"}],"tags":[],"related":[],"cancers":["endometrial"],"sections":[],"technologies":[],"targets":["her2","tp53"],"drugs":["trastuzumab-deruxtecan","trastuzumab"],"companies":[],"institutions":[],"pathways":[],"terms":["endometrial-molecular-classes"],"trials":["destiny-pantumor02"],"people":[],"bottlenecks":[],"keyPapers":["paper-yarden-sliwkowski-erbb-network-nrmcb-2001"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Adding T-DXd (or trastuzumab) to first-line chemo-immunotherapy in HER2-positive p53abn endometrial cancer improves PFS and OS.","rationale":"Strong single-agent activity, a defined biomarker, and a subtype with the highest mortality and least benefit from immunotherapy.","test":"Randomised phase 3 of chemo-IO ± T-DXd (or sequential T-DXd) in HER2 IHC 2+/3+ p53abn disease; NRG-GY026 tests trastuzumab/pertuzumab with chemotherapy.","maturity":"early-clinical"},{"id":"idea-bio1-organoid-assay-clinical-validation","kind":"idea","name":"Hold organoid drug tests to the same standard as a diagnostic test","aka":[],"tldr":"Lab-grown mini-tumours are already being sold to guide treatment, but the tests are not validated like other medical tests. They should be.","summary":"Functional drug-response assays are entering clinical use without the analytical validation (precision, repeatability, reference ranges, failure rate reporting) or clinical validation (prospective outcome correlation) required of companion diagnostics. The proposal is a formal assay validation framework, developed with regulators, defining minimum performance, standardised reporting of derivation success rate, and mandatory registry submission of predictions and outcomes.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Lab models that fail to predict what happens in patients): Wong, Siah & Lo, Estimation of clinical trial success rates (Biostatistics 2019)","url":"https://doi.org/10.1093/biostatistics/kxx069"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["functional-drug-testing","organoids","companion-diagnostic"],"targets":[],"drugs":[],"companies":["sengine","xilis","curesponse"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-preclinical-models","b-biomarker-validation","b-reproducibility"],"keyPapers":["paper-wong-biostatistics"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Applying a diagnostic-grade validation framework reveals substantial inter-laboratory variability in organoid drug-response calls, and standardisation improves concordance and predictive value.","rationale":"Similar frameworks converted next-generation sequencing panels from research assays into reimbursed diagnostics; the absence of one is why functional testing is still viewed sceptically.","test":"Ring trial in which five laboratories test identical samples with their own protocols; measure concordance and then repeat after adopting a common protocol.","maturity":"preclinical-evidence","actor":"regulator","cost":"small","horizonYears":3},{"id":"idea-acc-home-chemotherapy-older-patients","kind":"idea","name":"Home administration of selected chemotherapy and immunotherapy for older and frail patients","aka":[],"tldr":"For frail older patients, the journey to hospital can be the hardest part of treatment. Nurses can safely give some cancer treatments at home, which may help more people complete their course.","summary":"Home chemotherapy programmes exist in several countries for low-risk regimens and for subcutaneous formulations of antibodies, with high patient satisfaction and safety. For older and frail patients, travel and waiting are major causes of missed doses and early discontinuation. Extending home delivery to this group, with remote monitoring and clear escalation routes, could improve completion and quality of life; payment models are the main barrier.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Older and multimorbid patients are excluded and undertreated): Mohile et al., Evaluation of geriatric assessment and management on toxic effects of cancer treatment (GAP70+, Lancet 2021)","url":"https://doi.org/10.1016/S0140-6736(21)01789-X"}],"tags":[],"related":[],"cancers":[],"sections":["chemotherapy"],"technologies":["cytotoxic-chemotherapy","monoclonal-antibody"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-aging-comorbidity","b-care-fragmentation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Home administration for eligible patients over 75 will increase treatment completion by at least 15 percentage points and reduce patient-reported treatment burden, with equivalent safety.","rationale":"Home delivery of complex therapies (dialysis, parenteral nutrition, IV antibiotics) is safe and preferred by patients; oncology has lagged for institutional rather than clinical reasons.","test":"A randomised trial of home versus clinic administration for defined regimens in patients over 75, with completion, adverse events, quality of life, and cost as endpoints.","maturity":"being-tested-at-scale","actor":"payer","cost":"medium","horizonYears":3},{"id":"idea-acc-home-based-end-of-life-kits","kind":"idea","name":"Home end-of-life care kits and trained family carers where no hospice exists","aka":[],"tldr":"Most people in poorer countries die at home without any professional support. A simple kit of medicines and supplies plus a few hours of training for a family member could make dying far less painful.","summary":"Where community palliative services do not exist, families care for the dying with no medicines or guidance. A standardised home kit (oral morphine, anti-emetics, laxatives, wound and pressure-care supplies, an illustrated guide) issued at discharge with brief carer training and a phone line has been piloted in several African settings. Defining the kit, training, and supply chain, and evaluating it rigorously, could produce a scalable minimum standard.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Pain relief and palliative care are unavailable to most): WHO fact sheet, Palliative care","url":"https://www.who.int/news-room/fact-sheets/detail/palliative-care"}],"tags":[],"related":["idea-acc-local-oral-morphine-production"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-palliative","b-global-access"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Families receiving a kit and training will report significantly lower patient pain and distress in the last weeks of life and fewer emergency hospital visits than families receiving standard discharge.","rationale":"Family caregivers already provide most end-of-life care; equipping and training them is the only feasible model at scale in many settings.","test":"A cluster-randomised trial across 20 hospitals discharging patients with advanced cancer, with carer-reported pain and distress and unplanned readmission as endpoints.","maturity":"early-clinical","actor":"philanthropy","cost":"small","horizonYears":2},{"id":"idea-tr1-home-infusion-trial-drugs","kind":"idea","name":"Home infusion and local blood draws for trial drugs after the first cycles","aka":[],"tldr":"Once a patient has safely had the first few doses of a trial drug at the hospital, later doses could be given at home or a local clinic, with blood tests done nearby, so distance no longer decides who can join.","summary":"Protocols pre-specify a decentralised phase: after two or three supervised cycles, eligible patients receive subcutaneous or infused trial drug via home-infusion nursing or a local clinic under the site investigator's oversight, with labs at community draw stations, ePRO-based toxicity capture and telehealth visits. Pandemic-era regulatory flexibilities showed feasibility; the idea is to write it into protocols by default for drugs with predictable safety.","asOf":"2026-09-08","links":[{"label":"FDA Oncology Center of Excellence: Project Community (archived copy)","url":"https://web.archive.org/web/20250115091955/https://www.fda.gov/about-fda/oncology-center-excellence/project-community"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["checkpoint-inhibitor","monoclonal-antibody"],"targets":[],"drugs":["pembrolizumab","nivolumab","trastuzumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-enrolment","b-trial-diversity"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Trials with a decentralised phase will enrol a higher share of patients living more than 60 minutes from the site and have lower dropout, with no increase in protocol deviations affecting the primary endpoint.","rationale":"Travel burden is one of the most cited reasons for declining trials. Home administration of biologics is routine in rheumatology and haemophilia, and subcutaneous formulations of checkpoint inhibitors and anti-HER2 antibodies exist.","test":"Randomise consenting patients at cycle 3 to continued site visits versus home/local administration in a phase 3 trial of an established biologic class, comparing retention, deviations and patient-reported burden.","maturity":"early-clinical","actor":"industry","cost":"medium","horizonYears":3},{"id":"idea-prev-frail-elderly-primary-endocrine-breast","kind":"idea","name":"Hormone tablets instead of surgery for small breast cancers in the frail over-80s","aka":[],"tldr":"Frail women over 80 with small hormone-sensitive breast cancers may do as well with a daily tablet as with surgery. A trial would define who can safely avoid the operation.","summary":"Older trials of primary endocrine therapy showed equal survival but more local progression; modern imaging and aromatase inhibitors change the calculus. Propose an RCT in women aged 80 and over with ER-positive tumours under 2 cm and frailty, comparing primary endocrine therapy with surgery, with quality of life and overall survival endpoints.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Overdiagnosis and false alarms): Welch & Black, Overdiagnosis in cancer (JNCI 2010)","url":"https://doi.org/10.1093/jnci/djq099"}],"tags":[],"related":[],"cancers":["breast-hr-positive"],"sections":["hormonal"],"technologies":["endocrine-therapy","geriatric-assessment"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-overdiagnosis","b-aging-comorbidity"],"keyPapers":["paper-welch-j-natl-cancer-inst"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Primary endocrine therapy is non-inferior for overall survival at five years and superior for quality of life and independence.","rationale":"Competing mortality dominates; post-surgical functional decline is common in the frail.","test":"800-patient pragmatic RCT.","maturity":"early-clinical","actor":"clinic","cost":"medium","horizonYears":6},{"id":"idea-acc-hospital-at-home-oncology","kind":"idea","name":"Hospital-at-home for oncology: treating low-risk febrile neutropenia and dehydration at home","aka":[],"tldr":"Hospital-at-home programmes deliver intravenous antibiotics, fluids, monitoring and daily nurse and physician visits in the patient's home, with equivalent or better outcomes and lower costs in general medicine. Extending them to low-risk fever after chemotherapy and dehydration, with payer recognition, would keep older cancer patients out of hospital beds, where they are most at risk of harm.","summary":"Hospital-at-home programmes deliver acute-level care (IV antibiotics, fluids, monitoring, daily nurse and physician oversight) in the patient's home and have shown equivalent or better outcomes, fewer complications, and lower costs in general medicine. Oncology-specific programmes (such as Huntsman at Home) report reduced admissions and emergency visits. Expanding the model to defined oncology conditions, with payer recognition, would reduce hospitalisation, which is particularly harmful for older patients.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Older and multimorbid patients are excluded and undertreated): Mohile et al., Evaluation of geriatric assessment and management on toxic effects of cancer treatment (GAP70+, Lancet 2021)","url":"https://doi.org/10.1016/S0140-6736(21)01789-X"}],"tags":[],"related":["idea-acc-acute-oncology-assessment-units"],"cancers":[],"sections":["supportive-care"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-aging-comorbidity","b-care-fragmentation","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Oncology hospital-at-home will reduce inpatient bed-days for eligible conditions by at least 40% with no increase in 30-day mortality or escalation, and higher patient satisfaction.","rationale":"Hospital stays cause deconditioning, delirium, and infection in older patients; the interventions for many oncology admissions are deliverable at home.","test":"A randomised trial of hospital-at-home versus admission for low-risk febrile neutropenia, dehydration, and symptom crises in 500 patients with bed-days, safety, and satisfaction as endpoints.","maturity":"being-tested-at-scale","actor":"clinic","cost":"medium","horizonYears":3},{"id":"idea-fund-public-car-t-manufacturing","kind":"idea","name":"Hospital-based CAR-T manufacturing at cost through a public network","aka":[],"tldr":"Academic hospitals can already make CAR-T cells for a fraction of the commercial price. A public network would scale that so more patients can be treated for less.","summary":"Point-of-care manufacturing of CAR-T and other autologous cell therapies in a network of accredited academic hospitals, using shared vectors, harmonised processes and closed automated systems, with regulatory approval as a hospital-exemption or public product rather than a commercial licence. Spain's ARI-0001 (Hospital Clínic Barcelona) was approved by the national agency as a hospital-made CD19 CAR-T at a reported cost far below commercial products; India and Brazil have followed with domestic academic products. A network would share process, quality and pharmacovigilance and could supply public health systems at cost.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Incentives reward me-too drugs and marginal gains): Upadhaya et al., PD1/PDL1 inhibitor clinical trial landscape (Nat Rev Drug Discov 2022)","url":"https://doi.org/10.1038/d41573-022-00030-4"}],"tags":[],"related":["idea-fund-pay-for-cure-annuities","idea-fund-hospital-exemption-registry"],"cancers":["dlbcl","all-leukemia","multiple-myeloma"],"sections":[],"technologies":["car-t","allogeneic-cell-therapy"],"targets":["cd19","bcma"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["cartitude-4","karmma-3","nct06413498","nct06464991","zuma-7"],"people":[],"bottlenecks":["b-incentive-misalignment","b-manufacturing-cell-therapy","b-drug-pricing"],"keyPapers":["paper-upadhaya-nat-rev-drug-discov","paper-cd19-all-leukemia-j-clin-invest-2016","paper-cd19-all-leukemia-j-clin-oncol-2014","paper-cd19-all-leukemia-blood-2015"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A ten-hospital public CAR-T network delivers CD19 and BCMA CAR-T with efficacy and safety non-inferior to commercial products in registry comparison, at a fully-loaded cost per treated patient under a third of commercial list prices, and doubles the number of eligible patients treated in its regions within four years.","rationale":"ARI-0001 and academic products elsewhere demonstrate feasibility and regulatory acceptance; academic manufacturing removes the margin and much of the logistics cost. Capacity, not biology, currently rations CAR-T in most of the world.","test":"Fund a five-centre pilot with a shared vector and process, register a prospective comparative registry against commercial products, and report outcomes and cost at three years.","maturity":"early-clinical","actor":"clinic","cost":"large","horizonYears":4},{"id":"idea-fund-hospital-exemption-registry","kind":"idea","name":"Hospital-exemption cell therapies at scale, backed by a shared registry","aka":[],"tldr":"European law already lets hospitals make advanced therapies for their own patients. Pair that with a shared outcomes registry so academic CAR-Ts and similar treatments can prove themselves without a commercial licence.","summary":"The EU hospital exemption (and analogous national point-of-care manufacturing provisions in the UK, Spain, Japan and elsewhere) permits non-routine manufacture of advanced therapy medicinal products for individual patients under national oversight. It is used unevenly and generates little comparable evidence. The proposal is a harmonised framework: common quality standards, a mandatory prospective registry with standard outcome and toxicity capture, and a defined pathway by which registry evidence supports wider use or a conditional marketing authorisation. This lets academic products reach patients years earlier and creates a real-world evidence base for regulators.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The valley of death between lab and product): Butler, Translational research: crossing the valley of death (Nature 2008)","url":"https://doi.org/10.1038/453840a"}],"tags":[],"related":["idea-fund-public-car-t-manufacturing","idea-fund-translational-institutes-gmp"],"cancers":[],"sections":[],"technologies":["car-t","tcr-t","til-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":["vall-dhebron","nki","charite"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-translational-valley","b-manufacturing-cell-therapy","b-regulatory-fragmentation"],"keyPapers":["paper-butler-nature"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A harmonised hospital-exemption registry across ten European centres captures outcomes for more than 90% of treated patients and supports at least one conditional authorisation or national reimbursement decision for an academic cell therapy within four years.","rationale":"Spain's approval of ARI-0001 under hospital exemption shows the route can deliver a reimbursed academic CAR-T; the European Medicines Agency and national agencies have called for better evidence from exempted products. Registry-based approval pathways exist in Japan for regenerative medicine.","test":"Establish the registry and standards in a pilot consortium and evaluate data completeness, comparability with pivotal trial outcomes and regulatory uptake at three years.","maturity":"early-clinical","actor":"regulator","cost":"medium","horizonYears":3},{"id":"idea-fund-protected-time-physician-scientists","kind":"idea","name":"Hospital-funded protected time for clinician-scientists, repaid by trial revenue","aka":[],"tldr":"Doctors who could turn discoveries into trials are buried in clinical work. Hospitals would guarantee them research time and recover the cost from the trials and grants they bring in.","summary":"Cancer hospitals create a protected-time scheme (for example 40% for five years) for clinician-scientists leading translational projects, funded from a revolving pool seeded by philanthropy and repaid from the indirect costs of grants and per-patient trial income those clinicians generate. Selection is by translational plan and mentorship, not by publication record. Clinician-scientists are the people who take a lab finding into a phase 1 protocol, yet their numbers are falling in most countries because clinical productivity pays and research time is the first thing cut.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The valley of death between lab and product): Butler, Translational research: crossing the valley of death (Nature 2008)","url":"https://doi.org/10.1038/453840a"}],"tags":[],"related":["idea-fund-translational-fellowships","idea-fund-surgeon-scientist-pathway"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-translational-valley","b-workforce"],"keyPapers":["paper-butler-nature"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Clinicians with guaranteed protected time initiate at least twice as many investigator-led trials and translational grants per head as matched colleagues without protected time, and the scheme becomes cost-neutral to the hospital within five years through recovered indirect costs and trial income.","rationale":"NIH's physician-scientist workforce report documents the decline; where protected time has been funded (Howard Hughes, Burroughs Wellcome career awards, UK academic clinical lecturer posts) retention and output are markedly higher. Trial income is a real revenue line at cancer centres and can be earmarked.","test":"Two cancer centres run the scheme for five years with financial tracking and compare trial initiations and grant income of protected clinicians with a matched internal control group.","maturity":"speculative","actor":"clinic","cost":"medium","horizonYears":4},{"id":"idea-reg-point-of-care-cart-network","kind":"idea","name":"Hospital-made CAR-T under one shared regulatory master file","aka":[],"tldr":"Instead of shipping a patient's cells to a distant factory, hospitals would make CAR-T on site under a shared licence, cutting cost and waiting time.","summary":"Academic point-of-care CAR-T already exists: ARI-0001 (Hospital Clinic Barcelona, approved under Spain's hospital exemption at roughly a third of commercial cost), NexCAR19 in India (ImmunoACT, list price around $40,000) and several Chinese and Israeli programmes. The MHRA's 2025 framework for point-of-care and modular manufacturing allows one authorisation to cover multiple hospital sites under a central control site. The proposal is a network of 20-30 hospital GMP suites making a common CD19 (and later BCMA) product from a shared master file, with pooled release testing data and a single outcomes registry.","asOf":"2026-09-08","links":[{"label":"MHRA point of care manufacturing framework (page moved; nearest live section)","url":"https://www.gov.uk/government/news/"}],"tags":[],"related":[],"cancers":["dlbcl","all-leukemia","multiple-myeloma"],"sections":[],"technologies":["car-t"],"targets":["cd19","bcma"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["cartitude-4","karmma-3","nct06413498","nct06464991","zuma-7"],"people":[],"bottlenecks":["b-manufacturing-cell-therapy","b-drug-pricing"],"keyPapers":["paper-cd19-all-leukemia-j-clin-invest-2016","paper-cd19-all-leukemia-j-clin-oncol-2014","paper-cd19-all-leukemia-blood-2015"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Network-manufactured CAR-T achieves a vein-to-vein time under 14 days and a fully loaded cost per dose below $100,000 while matching the complete response rate and cytokine release syndrome profile of commercial products in the same indication.","rationale":"The cost of autologous CAR-T is dominated by logistics, single-site capital and margin, not materials. Closed automated devices (CliniMACS Prodigy, Cocoon) make hospital manufacture reproducible, and a shared master file spreads the regulatory burden that no single hospital could carry.","test":"Fund a ten-hospital pilot in one health system with a shared control site and master file; compare vein-to-vein time, manufacturing failure rate, cost and 12-month outcomes with contemporaneous commercial CAR-T recipients in the same system.","maturity":"early-clinical","actor":"clinic","cost":"large","horizonYears":4},{"id":"idea-hpv-ctdna-cervical","kind":"idea","name":"HPV circulating tumour DNA to guide cervical cancer therapy","aka":[],"tldr":"Because cervical tumours carry viral DNA that normal cells do not, a blood test for HPV DNA is a near-perfect tumour marker for tracking response and relapse.","summary":"Cervical tumours carry HPV DNA that normal cells do not, so a blood test for HPV ctDNA is a near-perfect tumour marker, and this idea would use it to steer therapy. Plasma HPV ctDNA measured by droplet digital PCR or sequencing is detectable in most locally advanced cases, falls during chemoradiation, and predicts relapse months before imaging, as shown by Cabel, Han and others. The hypothesis is that persistent HPV ctDNA at the end of chemoradiation identifies the patients who benefit from adjuvant pembrolizumab, while undetectable ctDNA allows maintenance to be omitted. The rationale is a tumour-specific analyte with zero background measured by cheap PCR, which would make the KEYNOTE-A18 benefit affordable; the test is a ctDNA-stratified randomised trial, at an early clinical stage.","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT04221945: KEYNOTE-A18 / ENGOT-cx11 / GOG-3047","url":"https://clinicaltrials.gov/study/NCT04221945"}],"tags":[],"related":[],"cancers":["cervical"],"sections":[],"technologies":["liquid-biopsy","mrd-testing"],"targets":[],"drugs":["pembrolizumab"],"companies":[],"institutions":[],"pathways":[],"terms":["mrd","ctdna"],"trials":["keynote-a18"],"people":[],"bottlenecks":[],"keyPapers":["paper-keynote-a18-os-lancet-2024","paper-keynote-a18-pfs-lancet-2024"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Persistent HPV ctDNA at the end of chemoradiation identifies patients who benefit from adjuvant immunotherapy, and undetectable ctDNA allows omission of pembrolizumab maintenance.","rationale":"Tumour-specific analyte with essentially zero background; cheap PCR; would make KEYNOTE-A18's benefit affordable by targeting it.","test":"Prospective ctDNA-stratified randomisation of maintenance pembrolizumab after chemoradiation; primary endpoint PFS.","maturity":"early-clinical"},{"id":"idea-acc-hpv-self-sample-same-day-ablation","kind":"idea","name":"HPV self-testing with same-day treatment as the national cervical programme","aka":[],"tldr":"Women can collect their own sample for the virus that causes cervical cancer; those who test positive can be treated the same day with a simple heat device. Done nationally, this could eliminate a disease that still kills hundreds of thousands of women a year.","summary":"WHO's cervical cancer elimination strategy sets 70% screening coverage with a high-performance test and 90% treatment of pre-cancer. Self-collected HPV testing removes the speculum exam that deters women, and portable thermal ablation allows treatment at the point of screening without histology. Point-of-care HPV tests now return results within an hour. The proposal is to make this combination, rather than cytology, the default national programme and fund it as a vertical campaign.","asOf":"2026-09-08","links":[{"label":"WHO cervical cancer elimination initiative","url":"https://www.who.int/initiatives/cervical-cancer-elimination-initiative"}],"tags":[],"related":[],"cancers":["cervical"],"sections":["prevention"],"technologies":["hpv-vaccine"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-global-access","b-prevention-adoption"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Countries implementing self-sampling plus same-day ablation will reach 70% screening coverage of women aged 35-45 within five years, versus under 20% for cytology-based programmes, and will halve pre-cancer treatment loss to follow-up.","rationale":"Self-sampling roughly doubles participation in trials in Africa and Latin America; screen-and-treat eliminates the second visit that loses most patients.","test":"National rollout with population coverage, positivity, same-day treatment rate, and cervical cancer incidence tracked in the population-based registry over ten years.","maturity":"being-tested-at-scale","actor":"policy","cost":"medium","horizonYears":3},{"id":"idea-bio1-immune-matched-humanised-mice","kind":"idea","name":"Humanised mice with an immune system matched to the tumour donor","aka":[],"tldr":"Most cancer drugs are tested in mice with no immune system, then given to people who have one. Mice carrying the same patient's immune cells and tumour would be a fairer test.","summary":"Standard PDX models use immunodeficient mice, which cannot evaluate immunotherapy or immune-mediated toxicity. Humanised immune system mice reconstituted with HLA-matched or autologous haematopoietic cells, ideally with human cytokine knock-in backgrounds to support myeloid development, allow tumour and immune system from the same donor. Cost and reproducibility have kept them niche.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Lab models that fail to predict what happens in patients): Wong, Siah & Lo, Estimation of clinical trial success rates (Biostatistics 2019)","url":"https://doi.org/10.1093/biostatistics/kxx069"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["pdx-models","checkpoint-inhibitor"],"targets":[],"drugs":[],"companies":["champions-oncology"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-preclinical-models","b-immunotherapy-response"],"keyPapers":["paper-wong-biostatistics"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Autologous or HLA-matched humanised models reproduce the individual patient's response and immune-related toxicity to checkpoint blockade better than chance, measured against the patient's actual outcome.","rationale":"Immune context determines the outcome of most modern oncology drugs; syngeneic mouse tumours are immunologically unlike human cancers and have repeatedly over-predicted benefit.","test":"Build 40 paired autologous models from patients starting checkpoint therapy and score concordance between model response and patient outcome, pre-registering the concordance threshold.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":5},{"id":"idea-hcc-io-before-transplant","kind":"idea","name":"Immunotherapy downstaging to transplant with a safe washout","aka":[],"tldr":"Use immunotherapy to shrink liver cancer enough for a transplant, and find the safe gap between the last dose and surgery so the new liver is not rejected.","summary":"The idea is to use checkpoint inhibitors such as nivolumab or atezolizumab to shrink hepatocellular carcinoma enough for liver transplantation, and to define the safe gap between the last dose and surgery so the new liver is not rejected. Checkpoint inhibitors persist on T cells for months, so the risk is time-dependent and measurable; case series report rejection when PD-1 antibodies are given within weeks of transplant, others successful downstaging. The hypothesis is that a washout of at least three months, timed by receptor occupancy or ctDNA, allows safe transplantation with recurrence-free survival equal to conventionally downstaged patients. The test is a prospective single-arm trial with protocolised washout and biopsy-proven rejection as the safety endpoint.","asOf":"2026-09-07","links":[{"label":"Tabrizian et al., PD-1 inhibitor as bridge therapy to liver transplantation? (American Journal of Transplantation 2021)","url":"https://doi.org/10.1111/ajt.16448"}],"tags":[],"related":[],"cancers":["hcc"],"sections":[],"technologies":["liver-transplant-oncology","checkpoint-inhibitor"],"targets":[],"drugs":["nivolumab","atezolizumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["checkmate-9dw","imbrave050","imbrave150","nct03755791","nct05904886"],"people":[],"bottlenecks":[],"keyPapers":["paper-tabrizian-am-j-transplant","paper-imbrave150-nejm-2020","paper-atezolizumab-hcc-j-hepatol-2022","paper-nivolumab-hcc-jama-oncol-2020"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A washout of at least three months after PD-(L)1 blockade, with pre-transplant PD-1 receptor-occupancy or ctDNA-guided timing, allows safe transplantation with recurrence-free survival equal to conventionally downstaged patients.","rationale":"Checkpoint inhibitors persist on T cells for months; the immunologic risk is time-dependent and measurable.","test":"Prospective single-arm trial with protocolised washout and biopsy-proven rejection as the primary safety endpoint; compare to historical downstaging cohorts.","maturity":"early-clinical"},{"id":"idea-bio2-implantable-microdevice-screen","kind":"idea","name":"Implant a tiny device that tests twenty drugs inside the patient's own tumour","aka":[],"tldr":"A rice-grain-sized implant releases microdoses of up to 20 drugs into separate spots of a tumour for one to three days, then is removed so pathologists can see which drug worked in that person's own tumour. First-in-human studies have been done in breast, sarcoma and brain tumours.","summary":"Implantable microdevices developed at MIT and Brigham and Women's Hospital deliver microdoses of up to 20 agents into spatially separated tumour regions for 24-72 hours before retrieval and analysis, and first-in-human studies have been performed in breast, sarcoma and brain tumours. Applied to immune-modulating agents, the device measures local pharmacodynamics in the real human microenvironment, which no model reproduces.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Cold tumours and the immunosuppressive microenvironment): Haslam & Prasad, Estimation of the percentage of US patients eligible for and responding to checkpoint inhibitors (JAMA Netw Open 2019)","url":"https://doi.org/10.1001/jamanetworkopen.2019.2535"}],"tags":[],"related":[],"cancers":["sarcoma","glioblastoma","tnbc"],"sections":[],"technologies":["functional-drug-testing","single-cell-spatial","checkpoint-inhibitor"],"targets":[],"drugs":[],"companies":[],"institutions":["dana-farber","mgh"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-tme-immunosuppression","b-combination-space","b-preclinical-models"],"keyPapers":["paper-haslam-jama-netw-open"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Microdevice-derived local response ranking predicts subsequent systemic response to the same agent, giving a functional assay for immunotherapy combinations that tissue genomics cannot provide.","rationale":"The core problem in combination immunotherapy is a combinatorial space far larger than trial capacity. In-patient microdosing tests many agents per patient rather than one, converting an intractable search into a measurable screen.","test":"Prospective study in patients scheduled for resection: implant, retrieve, profile, then follow subsequent systemic therapy outcomes to test the concordance between local ranking and clinical response.","maturity":"early-clinical","actor":"engineering","cost":"medium","horizonYears":5},{"id":"idea-bio1-in-silico-trials-dose","kind":"idea","name":"In silico trials to choose the dose before the first patient","aka":[],"tldr":"Simulating thousands of virtual patients on a computer can suggest which dose and schedule to test, so fewer real patients receive doses that are too high or too low.","summary":"Quantitative systems pharmacology and mechanistic tumour growth models, calibrated on prior trial data, can simulate exposure-response across virtual populations. Regulators already accept model-informed drug development for paediatric extrapolation and some dosing decisions. Project Optimus requires dose optimisation; simulation could narrow the candidate schedules before the randomised dose-comparison stage, saving patients and time.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Lab models that fail to predict what happens in patients): Wong, Siah & Lo, Estimation of clinical trial success rates (Biostatistics 2019)","url":"https://doi.org/10.1093/biostatistics/kxx069"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["ai-drug-design"],"targets":[],"drugs":[],"companies":["insilico-medicine"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-preclinical-models","b-dose-optimisation"],"keyPapers":["paper-wong-biostatistics"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"For agents where a model-informed schedule was proposed prospectively, the simulation-selected dose matches the eventually recommended phase 2 dose more often than the traditional maximum tolerated dose approach.","rationale":"Most oncology drugs were historically dosed too high; the exposure-response and toxicity data needed for simulation usually exist by end of phase 1 but are analysed informally.","test":"Retrospective blinded simulation of 20 agents with known optimised doses, then prospective use in three phase 1 programmes with the model prediction locked before dose expansion.","maturity":"speculative","actor":"regulator","cost":"small","horizonYears":4},{"id":"idea-data-in-silico-trials-calibrated","kind":"idea","name":"In silico trials to prioritise combinations, scored against later real trials","aka":[],"tldr":"Simulate trials of drug combinations in populations of virtual patients to decide which real trials to run, and keep score of how often the simulations were right.","summary":"The number of possible combinations far exceeds trial capacity. Simulated trials using mechanistic and machine-learned models of virtual patient populations could rank combinations, but their predictive value is unknown. The proposal is a scored programme: simulations are registered with predicted effect sizes for combinations entering real phase 2 or 3 trials, and outcomes are compared as trials read out, building a public track record that determines how much weight simulation gets in portfolio decisions.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (AI that is built but not validated or deployed): Wu et al., How medical AI devices are evaluated: limitations and recommendations from an analysis of FDA approvals (Nature Medicine 2021)","url":"https://doi.org/10.1038/s41591-021-01312-x"}],"tags":[],"related":["idea-data-digital-twin-predict-then-observe","idea-data-open-cell-foundation-model"],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-ai-validation","b-combination-space","b-trial-design"],"keyPapers":["paper-wu-nat-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Simulation rankings will correlate positively with real trial outcomes for at least some drug classes, allowing a measurable reduction in failed phase 3 combination trials when used to filter candidates.","rationale":"Regulators already accept in silico evidence for device testing and some pharmacokinetic questions; the missing element for efficacy is a track record, which only forward scoring can build.","test":"Register predictions for 50 ongoing combination trials; compare with outcomes as they read out over four years; publish the correlation and calibration.","maturity":"speculative","actor":"research","cost":"medium","horizonYears":4},{"id":"idea-in-vivo-car-solid","kind":"idea","name":"In vivo CAR-T against solid-tumour antigens","aka":[],"tldr":"If a lipid nanoparticle can make CAR-T cells inside the body for lymphoma, it could be redosed weekly against solid-tumour targets that autologous CAR-T cannot sustain.","summary":"If a lipid nanoparticle can make CAR-T cells inside the body for lymphoma, this idea redoses it weekly against Claudin 18.2 and Glypican-3 in gastric, liver and pancreatic cancer. Solid-tumour CAR-T fails partly through exhaustion and poor persistence of a single infused product, whereas transient, redosable in vivo CAR expression could deliver repeated waves of fresh effector cells, limit off-tumour toxicity, avoid lymphodepletion and remove manufacturing delay. The test is a phase 1 in CLDN18.2-positive gastric cancer after the satricabtagene autoleucel proof of concept, measuring CAR-positive T-cell frequency, tumour infiltration and toxicity per dose. Speculative in maturity, it addresses the bottleneck Manufacturing cost and time for living and radioactive medicines.","asOf":"2026-09-04","links":[{"label":"Pfeiffer et al., In vivo generation of human CD19-CAR T cells (EMBO Molecular Medicine 2018)","url":"https://doi.org/10.15252/emmm.201809158"}],"tags":[],"related":[],"cancers":["gastric","hcc","pancreatic"],"sections":[],"technologies":["in-vivo-car-t","car-t"],"targets":["cldn18-2","gpc3"],"drugs":["satricabtagene-autoleucel"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-pfeiffer-embo-mol-med","paper-gpc3-hcc-oncoimmunology-2016","paper-cldn18-gastric-front-oncol-2020","paper-gpc3-gastric-pathol-res-pract-2026"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Weekly in vivo CAR mRNA-LNP against CLDN18.2 or GPC3 produces response rates comparable to ex vivo CAR-T with lower toxicity and no manufacturing delay.","rationale":"Transient expression limits on-target off-tumour toxicity; repeated dosing avoids exhaustion of a single product; no lymphodepletion needed.","test":"Phase 1 in CLDN18.2+ gastric cancer after satri-cel proof of concept; measure CAR+ T-cell frequency, tumour infiltration, and toxicity per dose.","maturity":"speculative"},{"id":"idea-reg-in-vivo-cart-off-the-shelf-vial","kind":"idea","name":"In vivo CAR-T as a vial on the shelf: a cost and access trial in lymphoma","aka":[],"tldr":"Some new medicines reprogramme immune cells inside the body with an injection, skipping the factory entirely. Test whether that makes CAR-T affordable and available in ordinary hospitals.","summary":"In vivo CAR-T uses targeted lipid nanoparticles or engineered lentiviral vectors to deliver the CAR gene to T cells inside the patient (programmes from Interius, Umoja, Orna, Capstan and others entered the clinic in 2024-25). This idea is not about which antigen to hit but about manufacturing and delivery economics: a frozen vial produced in batches of thousands, administered in a community hospital with no apheresis, no bridging chemotherapy and possibly no lymphodepletion. A companion idea in this corpus covers solid-tumour antigens.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Manufacturing cost and time for living and radioactive medicines): Hernandez, Prasad & Gellad, Total costs of chimeric antigen receptor T-cell immunotherapy (JAMA Oncology 2018)","url":"https://doi.org/10.1001/jamaoncol.2018.0977"}],"tags":[],"related":["idea-in-vivo-car-solid"],"cancers":["dlbcl"],"sections":[],"technologies":["in-vivo-car-t","car-t"],"targets":["cd19"],"drugs":[],"companies":["interius","umoja-biopharma","orna-therapeutics"],"institutions":[],"pathways":[],"terms":[],"trials":["nct04094311","reliance","talicel-phase-1-2","zuma-1","zuma-7"],"people":[],"bottlenecks":["b-manufacturing-cell-therapy","b-global-access"],"keyPapers":["paper-hernandez-jama-oncol","paper-cd19-dlbcl-am-j-hematol-2021","paper-cd19-dlbcl-clin-cancer-res-2011","paper-cd19-dlbcl-cytotherapy-2020"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"An in vivo CD19 CAR-T product can be produced at a cost of goods below $10,000 per dose and delivered in non-academic centres with complete response rates in relapsed B-cell lymphoma within 15 percentage points of autologous CAR-T, and with a shorter time from decision to treatment.","rationale":"Batch manufacture of a nucleic acid-lipid product is the same industrial process that produced billions of mRNA vaccine doses; the marginal cost is orders of magnitude below a bespoke cell product, and the logistics collapse to a cold chain.","test":"Phase 2 in relapsed large B-cell lymphoma at community and academic sites, with pre-specified endpoints for cost of goods, time from enrolment to infusion, and response rate; compare with matched autologous CAR-T recipients.","maturity":"early-clinical","actor":"industry","cost":"large","horizonYears":4},{"id":"idea-moon-in-vivo-cart-generic-price","kind":"idea","name":"In vivo CAR-T manufactured and priced like a generic biologic","aka":[],"tldr":"Instead of making cell therapy from each patient's own cells in a factory, inject a particle that reprograms immune cells inside the body, made in bulk, so a dose costs thousands rather than hundreds of thousands.","summary":"Autologous CAR-T costs hundreds of thousands of dollars and weeks of manufacturing per patient, restricting it to a small fraction of eligible patients in rich countries. In vivo CAR generation with lipid nanoparticles or targeted lentiviral vectors (Umoja, Interius, Orna and others) has entered the clinic in B-cell malignancies. The proposal is a coordinated programme to develop an in vivo CD19 or BCMA product with a manufacturing process and cost-of-goods target under $5,000 per dose, licensed for distribution through generic-style manufacturers in middle-income countries, with regulatory pathways agreed in advance.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Manufacturing cost and time for living and radioactive medicines): Hernandez, Prasad & Gellad, Total costs of chimeric antigen receptor T-cell immunotherapy (JAMA Oncology 2018)","url":"https://doi.org/10.1001/jamaoncol.2018.0977"}],"tags":[],"related":["idea-in-vivo-car-solid"],"cancers":["dlbcl","multiple-myeloma"],"sections":[],"technologies":["in-vivo-car-t","car-t"],"targets":["cd19","bcma"],"drugs":[],"companies":["umoja-biopharma","interius","orna-therapeutics"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-manufacturing-cell-therapy","b-global-access","b-drug-pricing"],"keyPapers":["paper-hernandez-jama-oncol","paper-bcma-multiple-myeloma-leukemia-2020","paper-cd19-multiple-myeloma-lancet-haematol-2019","paper-cd19-multiple-myeloma-blood-2020"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"An off-the-shelf in vivo CAR product achieves complete remission rates within 15 percentage points of autologous CAR-T in relapsed B-cell malignancies at less than a tenth of the delivered cost, enabling treatment of ten times as many patients.","rationale":"The cost of autologous therapy is in logistics and bespoke manufacturing, not in the biology; nucleic acid-lipid manufacturing scales like a vaccine.","test":"Phase 2 in relapsed large B-cell lymphoma with pre-specified cost-of-goods reporting and a parallel technology transfer to a manufacturer in India or Brazil.","maturity":"preclinical-evidence","actor":"industry","cost":"large","horizonYears":7},{"id":"idea-tr2-replication-before-ind","kind":"idea","name":"Independent replication of the key experiment before first-in-human academic trials","aka":[],"tldr":"Before a new cancer drug from a university is given to people, a separate laboratory should have repeated the main experiment showing it works.","summary":"Industry routinely replicates academic findings internally before investing, and reports that a majority fail. Academic and small-biotech investigational new drug applications rest on the originating lab's data. Requiring, or funding through translational programmes, an independent replication of the pivotal efficacy experiment (in the same model, blinded, pre-registered) before first-in-human dosing would catch non-reproducible programmes before patients are exposed.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Preclinical results do not reproduce): Errington et al., Investigating the replicability of preclinical cancer biology (eLife 2021)","url":"https://doi.org/10.7554/eLife.71601"}],"tags":[],"related":["idea-tr2-replication-set-aside","idea-tr2-multilab-preclinical"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-reproducibility","b-translational-valley"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"At least a quarter of pivotal efficacy experiments will fail independent replication, and programmes whose experiments replicated will show higher early clinical activity than historical academic-origin programmes.","rationale":"Amgen and Bayer reported that only 11 to 25% of landmark preclinical findings reproduced in their hands; nothing in the regulatory pathway checks this for academic sponsors.","test":"Fund replication for twenty academic programmes approaching investigational new drug submission through an existing translational accelerator; report replication rate and subsequent clinical outcomes.","maturity":"speculative","actor":"regulator","cost":"medium","horizonYears":3},{"id":"idea-bio2-inhaled-lung-niche-immunotherapy","kind":"idea","name":"Inhaled immune therapy to make the lung hostile to arriving tumour cells","aka":[],"tldr":"Breathing in an immune-activating drug could turn the lungs into bad soil for cancer seeds, at doses far too low to cause body-wide side-effects.","summary":"Inhaled GM-CSF was tested in paediatric osteosarcoma lung metastases and inhaled interleukin-2 in renal cancer, both with local immune activation, acceptable safety and underpowered efficacy. Modern versions (an inhaled interleukin-15 superagonist, an inhaled STING agonist or an inhaled anti-CD47) could be aimed at lung-metastasis prevention rather than treatment, where the target cell burden is tiny.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Metastasis is understood least and studied last): Dillekås et al., Are 90% of deaths from cancer caused by metastases? (Cancer Medicine 2019)","url":"https://doi.org/10.1002/cam4.2474"}],"tags":[],"related":[],"cancers":["sarcoma","rcc"],"sections":[],"technologies":["cytokine-therapy","sting-agonist"],"targets":["cd47"],"drugs":[],"companies":["childrens-oncology-group"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-metastasis-biology","b-tme-immunosuppression"],"keyPapers":["paper-dillekas-cancer-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Inhaled alveolar immune activation after resection of a lung-tropic tumour halves lung-specific relapse without systemic cytokine toxicity.","rationale":"Metastasis prevention needs high local and low systemic exposure, and the lung is the only metastatic site with a direct non-invasive delivery route. Alveolar macrophage reprogramming is the mechanistic target and is measurable by bronchoalveolar lavage.","test":"A phase 1/2 in resected osteosarcoma or lung-tropic sarcoma with lavage-based pharmacodynamics, then a randomised trial with lung-relapse-free survival as the primary endpoint.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":6},{"id":"idea-moon-prebunking-at-diagnosis","kind":"idea","name":"Inoculate newly diagnosed patients against common cancer scams","aka":[],"tldr":"In the first weeks after diagnosis, tell patients plainly what kinds of false claims and expensive unproven clinics they will encounter and how to spot them.","summary":"Prebunking (inoculation) is effective in randomised studies for political and health misinformation: explaining manipulation techniques in advance reduces later susceptibility. Newly diagnosed patients are a predictable target of alternative clinics and supplement marketing. The proposal is a short prebunking module (video plus leaflet, delivered by the navigator or nurse) covering the common techniques (testimonials, suppressed-cure narratives, natural-equals-safe, fake experts) and how to raise anything with the team without judgement.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Misinformation and unproven therapies): Johnson et al., Cancer misinformation and harmful information on Facebook and other social media (JNCI 2022)","url":"https://doi.org/10.1093/jnci/djab141"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-misinformation","b-patient-voice"],"keyPapers":["paper-johnson-j-natl-cancer-inst"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Prebunked patients show lower susceptibility to unproven therapy claims at three months and are more likely to disclose supplement and alternative therapy use to their team.","rationale":"Technique-based inoculation generalises across claims, which matters because specific scams change constantly.","test":"Randomised trial at diagnosis in three centres; primary endpoint susceptibility score and disclosure at three months, secondary spending on unproven therapies.","maturity":"early-clinical","actor":"clinic","cost":"small","horizonYears":1},{"id":"idea-bio1-mrna-intrabodies","kind":"idea","name":"Instruct tumour cells to make antibodies against their own oncoprotein","aka":[],"tldr":"Deliver genetic instructions so the cancer cell itself manufactures a molecule that traps its driver protein inside the cell.","summary":"Intrabodies (single-domain antibodies or designed binders expressed intracellularly) can sequester or degrade targets that small molecules cannot reach. mRNA-LNP delivery makes transient intracellular expression feasible without viral vectors, and fusion to a degron converts binding into destruction. Delivery specificity and expression level are the open questions rather than the biology.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The undruggable drivers): Dang et al., Drugging the 'undruggable' cancer targets (Nature Reviews Cancer 2017)","url":"https://doi.org/10.1038/nrc.2017.36"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["neoantigen-mrna-vaccine","protac-degrader"],"targets":[],"drugs":[],"companies":["orna-therapeutics","moderna"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-undruggable-targets"],"keyPapers":["paper-dang-nat-rev-cancer"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"An mRNA-encoded degron-fused intrabody reduces its intracellular oncoprotein target by more than 60 percent in tumour tissue and inhibits growth in a xenograft after repeated dosing.","rationale":"Intrabody function is well established in cell culture; mRNA delivery has solved the manufacturing problem for intracellular proteins in other indications, and antibody-like binders can be raised against surfaces no small molecule can address.","test":"Mouse study comparing tumour and liver expression, target degradation and growth inhibition for an mRNA intrabody against a validated intracellular driver, with immunogenicity monitoring on repeat dosing.","maturity":"speculative","actor":"research","cost":"medium","horizonYears":9},{"id":"idea-field-interception","kind":"idea","name":"Intercept cancer at the field stage","aka":[],"tldr":"Whole regions of tissue carry cancer mutations long before a tumour exists. Detecting and treating the field, not the tumour, could prevent cancers rather than cure them.","summary":"This idea proposes intercepting cancer at the field stage: tissue regions carry cancer mutations long before a tumour exists, so treating the field could prevent cancers rather than cure them. Mutant clones in normal oesophagus, skin and airway are pervasive, and Barrett's ablation, HPV vaccination and Lynch aspirin already show interception works when the field is identifiable (Field cancerisation pathway). The hypothesis is that field markers such as TP53-mutant clone burden in Barrett's oesophagus or bronchial brushings identify people for whom ablation or chemoprevention cuts cancer incidence. The test is a randomised trial of marker-guided ablation against surveillance in non-dysplastic Barrett's, relevant to Oesophageal cancer and Non-small-cell lung cancer.","asOf":"2026-09-08","links":[{"label":"Martincorena et al., High burden and pervasive positive selection of somatic mutations in normal human skin (Science 2015)","url":"https://doi.org/10.1126/science.aaa6806"}],"tags":["mechanism","open-question"],"related":[],"cancers":["esophageal","nsclc","head-and-neck"],"sections":[],"technologies":["precancer-ablation","chemoprevention","endoscopic-resection"],"targets":["tp53"],"drugs":[],"companies":[],"institutions":["cruk","francis-crick"],"pathways":["field-cancerisation","clonal-evolution"],"terms":["barretts-esophagus"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-vogelstein-surfing-p53-network-nature-2000"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Molecular field markers (e.g., TP53-mutant clone burden in Barrett's or bronchial brushings) identify individuals for whom ablation or chemoprevention reduces cancer incidence.","rationale":"Sanger normal-tissue sequencing; Cytosponge and nasal-brushing assays make field sampling minimally invasive.","test":"Randomised trial of field-marker-guided ablation versus standard surveillance in non-dysplastic Barrett's with high TP53 clone burden; endpoint progression to dysplasia/cancer.","maturity":"early-clinical"},{"id":"idea-late-recurrence-interception","kind":"idea","name":"Intercepting late recurrence with ctDNA surveillance and oral SERDs","aka":[],"tldr":"Half of hormone-positive recurrences happen after year five. Blood tests during long-term follow-up could find them early and an oral SERD might stop them.","summary":"This speculative idea would run tumour-informed ctDNA surveillance, such as Signatera, in years 3 to 10 of adjuvant endocrine therapy for HR-positive breast cancer and randomise women with molecular relapse to an oral SERD such as camizestrant or giredestrant, with or without a CDK4/6 inhibitor. Many recurrences occur after year five, ctDNA anticipates clinical relapse by around a year in the c-TRAK TN and ZEST experience, and dormant micrometastases may still be endocrine-sensitive. The hypothesis is that treating molecular relapse this way delays or prevents clinical distant recurrence. The test would be a TREAT-ctDNA or ZEST-style trial, where feasibility of detection is the first hurdle; the idea addresses the dormancy and minimal residual disease bottleneck.","asOf":"2026-09-07","links":[{"label":"GALAXY: tumour DNA in blood four weeks after bowel cancer surgery predicts relapse tenfold (Nature Medicine 2023)","url":"https://doi.org/10.1038/s41591-022-02115-4"}],"tags":[],"related":[],"cancers":["breast-hr-positive"],"sections":[],"technologies":["mrd-testing"],"targets":[],"drugs":["camizestrant","giredestrant","signatera"],"companies":[],"institutions":[],"pathways":[],"terms":["late-recurrence","mrd"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-nct04214288-lancet-oncol-2024"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"ctDNA-detected molecular relapse treated with an oral SERD ± CDK4/6 inhibitor delays or prevents clinical distant recurrence versus standard care.","rationale":"ctDNA anticipates clinical relapse by a median of about a year in HR+ disease (c-TRAK TN, ZEST experience); dormant micrometastases may remain endocrine-sensitive.","test":"A TREAT-ctDNA / ZEST-style trial in HR+ disease with an oral SERD intervention; feasibility of detection rates during adjuvant ET is the first hurdle.","maturity":"speculative"},{"id":"idea-desmoid-intermittent-dosing","kind":"idea","name":"Intermittent or stop-and-restart nirogacestat in desmoid tumours","aka":[],"tldr":"Desmoid tumours are not cancers and often stop growing on their own; treating them indefinitely with a drug that causes ovarian failure may be more than needed.","summary":"Desmoid tumours are not cancers, do not metastasise and often stop growing on their own, yet nirogacestat, tested in the DeFi trial, is given continuously and causes ovarian failure. This idea proposes treating to best response, then pausing the drug and restarting only on progression. DeFi showed durable responses and ovarian toxicity that reverses when the drug is stopped, and a debate in JCO in 2026 has questioned long-term continuous use; the rationale is that toxicity depends on dose and duration and is reversible. The proposed test is a randomised discontinuation trial after twelve months of response with time to progression and ovarian function as co-primary endpoints; the idea is speculative and addresses the bottleneck of wrong doses, alongside the adaptive-therapy platform idea.","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT03785964: DeFi","url":"https://clinicaltrials.gov/study/NCT03785964"}],"tags":[],"related":[],"cancers":["sarcoma"],"sections":[],"technologies":[],"targets":[],"drugs":["nirogacestat"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["defi"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Treatment to best response followed by a drug holiday with restart on progression preserves disease control and fertility with fewer adverse events.","rationale":"Slow-growing, non-metastasising tumour; toxicity is dose-duration dependent and reversible.","test":"Randomised discontinuation trial after 12 months of response; time to progression and ovarian function as co-primary.","maturity":"speculative"},{"id":"idea-targeting-aneuploidy","kind":"idea","name":"Is aneuploidy itself a druggable vulnerability?","aka":[],"tldr":"Most cancers have the wrong number of chromosomes; normal cells do not. If that difference creates a specific weakness, a drug against it would spare normal tissue by definition.","summary":"This open question asks whether aneuploidy itself is a druggable vulnerability: most cancers have the wrong number of chromosomes and normal cells do not, so a drug against that difference would spare normal tissue. CIN cells depend on KIF18A, the spindle checkpoint, BCL-XL and proteostasis, and KIF18A inhibitors (sovilnesib, AMG 650) showed activity in platinum-resistant Ovarian cancer in 2024-25. The hypothesis is that a CIN score selects patients whose tumours regress on KIF18A or spindle-checkpoint therapy, and that STING modulators (cGAS-STING pathway) add immunity. The test is a randomised phase 2 of a KIF18A inhibitor against chemotherapy in CIN-high, TP53-mutant ovarian cancer; see also Whole-genome doubling (WGD).","asOf":"2026-09-08","links":[{"label":"Ben-David and Amon, Context is everything: aneuploidy in cancer (Nature Reviews Genetics 2019)","url":"https://doi.org/10.1038/s41576-019-0171-x"}],"tags":["mechanism","open-question"],"related":[],"cancers":["ovarian","tnbc"],"sections":[],"technologies":[],"targets":["tp53"],"drugs":[],"companies":[],"institutions":["francis-crick","mskcc","stanford"],"pathways":["chromosomal-instability","cgas-sting"],"terms":["whole-genome-doubling"],"trials":["nct03268382"],"people":[],"bottlenecks":[],"keyPapers":["paper-vogelstein-surfing-p53-network-nature-2000","paper-ben-david-nat-rev-genet"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A CIN score (from WGS or a FISH panel) selects patients whose tumours regress on KIF18A or SAC-directed therapy, and combination with STING-modulating agents converts CIN's immune tolerance into immunity.","rationale":"Sheltzer and Bakhoum lab data; the eDyNAmiC and TRACERx programmes provide biomarkers; early clinical responses in CIN-high ovarian cancer.","test":"Randomised phase 2 of a KIF18A inhibitor vs chemotherapy in CIN-high, TP53-mutant platinum-resistant ovarian cancer, with CIN score stratification and micronuclei/STING pharmacodynamics.","maturity":"early-clinical"},{"id":"idea-reg-joint-scientific-advice-default","kind":"idea","name":"Joint FDA-EMA-MHRA-PMDA scientific advice by default before pivotal cancer trials","aka":[],"tldr":"Before a company runs its phase 3 cancer trial, FDA, EMA, MHRA, PMDA, Health Canada and TGA would agree the endpoints, comparator, population and statistical plan in one joint written advice letter, so a single trial can support approval everywhere. Today parallel advice is used for a handful of products a year.","summary":"FDA-EMA parallel scientific advice exists but is used for a handful of products a year. The proposal is to make a joint written advice procedure covering endpoints, comparator, population and statistical plan the default for phase 3 oncology programmes, with PMDA, MHRA, Health Canada and TGA as standing participants. Advice would be recorded as a single agreed letter identifying any residual divergence, and divergence would be published in aggregate.","asOf":"2026-09-08","links":[{"label":"EMA-FDA parallel scientific advice (page moved; nearest live section)","url":"https://www.ema.europa.eu/en/human-regulatory-overview/research-development/scientific-advice-protocol-assistance/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-regulatory-fragmentation","b-trial-design"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Programmes with joint advice require fewer region-specific supplementary trials and reach approval in a second region a median of six months sooner than programmes with sequential single-agency advice.","rationale":"Most regional divergence in oncology approvals traces to disagreements over comparator, endpoint (PFS versus OS) or population fixed years earlier at design. Resolving them once, early, is cheaper than reconciling them at filing.","test":"Retrospectively compare approval divergence for products that used parallel advice with matched products that did not; then prospectively offer joint advice to all phase 3 oncology programmes for two years and track the same measures.","maturity":"early-clinical","actor":"regulator","cost":"small","horizonYears":3},{"id":"idea-tr2-data-link-enforcement","kind":"idea","name":"Journals check that data links actually work, and flag papers whose data vanish","aka":[],"tldr":"Papers say 'data available on request' or link to files that no longer exist. Journals should verify data access at publication and periodically afterwards, and mark papers whose data have disappeared.","summary":"Studies of data availability statements find that most 'available on request' data cannot be obtained, and that links decay within a few years. Automated checks at submission (resolvable repository DOI, non-empty dataset, matching description) and annual re-checks, with an expression of concern for papers whose data become unavailable, would make data sharing real rather than nominal.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Preclinical results do not reproduce): Errington et al., Investigating the replicability of preclinical cancer biology (eLife 2021)","url":"https://doi.org/10.7554/eLife.71601"}],"tags":[],"related":["idea-tr2-raw-image-deposit","idea-tr2-failed-trial-ipd-default"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-reproducibility","b-data-silos"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Enforcement raises the proportion of oncology papers with actually retrievable data from under 30% to over 80% within three years at adopting journals.","rationale":"Compliance follows verification: sequencing data deposit is near-universal because journals check accession numbers.","test":"Implement at two journals; sample papers annually and attempt retrieval; compare with non-adopting journals.","maturity":"early-clinical","actor":"policy","cost":"small","horizonYears":1},{"id":"idea-prostate-metastatic-presentation-as-the-screening-endpoint","kind":"idea","name":"Judge a prostate screening programme on metastatic presentation, not on incidence or mortality","aka":["metastasis-free survival screening endpoint prostate","metastatic presentation as screening outcome"],"tldr":"Screening trials are judged on deaths, which take fifteen years to count, and on cancers found, which is the wrong direction. Preventing a man from turning up with cancer already in his bones happens three times as often as preventing a death, arrives years earlier, and is the outcome he cares about.","summary":"The 2018 United States task force statement quantifies both: screening men aged 55 to 69 may prevent approximately 1.3 deaths from prostate cancer and approximately 3 cases of metastatic prostate cancer per 1,000 men screened over about 13 years. The metastatic endpoint is more than twice as frequent, and it precedes death by years, so a trial powered on it reads out sooner and smaller. It is also the endpoint that separates the benefit of screening from its harm: overdiagnosis inflates incidence, so incidence is actively misleading, and mortality is confounded by improvements in treatment over the decades a screening trial runs.\n\nDraisma showed that mean lead time is 5.4 to 6.9 years, which is the interval within which a metastatic presentation can be prevented and after which it cannot. The proposal is to adopt the rate of de novo metastatic presentation in the invited population as the primary outcome of any new prostate screening programme or trial, reported per 1,000 invited rather than per 1,000 screened, with prostate cancer mortality as a long-term secondary and incidence reported only as a harm. It is a change in what is measured rather than in what is done, which makes it cheap, and it would let the magnetic resonance imaging-first pathways such as Goteborg-2 be evaluated on a timescale on which policy can actually act.\n\nWhat any of this means for someone treated in Britain, from the screening committee's position and the NICE appraisals to scanner and radiotherapy capacity, waiting times and how to reach a trial, is on the UK and NHS pathway page for prostate cancer.","asOf":"2026-09-25","links":[],"tags":["prostate-evidence"],"related":["idea-prev-mri-first-prostate-screening-prs","idea-prev-prs-screening-start-age","early-detection-roadmap","prostate-roadmap"],"cancers":["prostate","prostate-low-risk","prostate-intermediate-risk","prostate-high-risk"],"sections":["early-detection","prevention"],"technologies":["prostate-screening-psa-mri","mri"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["screening","psa","overdiagnosis","metastasis-free-survival","lead-time-bias","overtreatment","number-needed-to-screen"],"trials":[],"people":[],"bottlenecks":["b-early-detection","b-overdiagnosis","b-trial-design","b-prevention-adoption"],"keyPapers":["paper-uspstf-prostate-screening-jama-2018","paper-schroder-erspc-screening-mortality-nejm-2009","paper-draisma-lead-time-overdiagnosis-psa-jnci-2009","paper-martin-jama","paper-goteborg-2-n-engl-j-med-2022","paper-loeb-overdiagnosis-overtreatment-prostate-eur-urol-2014"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"De novo metastatic presentation in the invited population is a valid and substantially more efficient primary endpoint for prostate cancer screening than prostate cancer mortality: it occurs roughly three times as often, precedes mortality by years, is not inflated by overdiagnosis, and would allow a screening pathway to be evaluated in about half the follow-up time with a comparable or smaller sample.","rationale":"Incidence is the wrong direction of merit in a disease where a quarter to two thirds of screen-detected cancers may be overdiagnosed, depending on definition and population; a programme that finds more cancers may be doing harm. Mortality is right but slow and confounded: over the 13 to 20 years a screening trial runs, treatment for metastatic disease has repeatedly improved, which dilutes the measured screening effect in a way that has nothing to do with the screening. Metastatic presentation is neither inflated by overdiagnosis nor rescued by better systemic therapy, it is the event that ends curative intent, and the task force's own numbers say it is about three times as common as a prevented death. Reporting per 1,000 invited rather than per 1,000 screened additionally makes uptake part of the measured outcome rather than an excuse for it.","test":"Two steps. First, a validation analysis in the existing randomised datasets: re-analyse ERSPC and the Cluster Randomised Trial of PSA Testing with de novo metastatic presentation as the endpoint and measure how many years earlier the observed effect reaches significance, and how closely the metastatic and mortality effects agree. Second, if the surrogacy holds, register metastatic presentation per 1,000 invited as the pre-specified primary outcome of the next generation of screening evaluations, including the magnetic resonance imaging-first pathways, with mortality retained as a long-term secondary. Step one is a secondary analysis of existing data and could be done in a year.","maturity":"speculative","actor":"policy","cost":"small","horizonYears":4},{"id":"idea-fund-programme-officer-incentives","kind":"idea","name":"Judge funding programme officers on burden alignment and trials completed","aka":[],"tldr":"The people who run funding programmes are judged on money moved and papers produced. Judge them instead on whether their portfolios match the burden of disease and whether the trials they fund finish.","summary":"Funders change the performance framework for programme staff and study sections: portfolio burden alignment, share of funded trials completing on time and publishing, replication rates of funded findings, data-sharing compliance and patient-relevant outcomes reached. Publish these metrics per programme. This is an inexpensive governance change that alters what gets steered towards funding without changing peer review itself.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Funding follows fashion, not burden): Carter & Nguyen, A comparison of cancer burden and research spending (BMC Cancer 2012)","url":"https://doi.org/10.1186/1471-2407-12-526"}],"tags":[],"related":["idea-fund-burden-weighted-portfolio","idea-fund-trial-completion-bonus"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["nci","cruk"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-funding-allocation","b-incentive-misalignment"],"keyPapers":["paper-sun-bmc-cancer"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Programmes whose officers are assessed on burden alignment and trial completion show measurable portfolio shift and higher trial completion within two funding cycles compared with programmes on conventional metrics.","rationale":"Incentives for intermediaries shape outcomes in development finance and venture capital; in science funding they have been left implicit. Trial non-completion runs at a fifth or more of academic oncology trials, and this is rarely counted against the programme that funded them.","test":"One funder adopts the metrics for half of its programmes (chosen at random) and compares portfolio and completion changes with the other half after two cycles.","maturity":"speculative","actor":"policy","cost":"small","horizonYears":2},{"id":"idea-prev-melanoma-ai-thick-melanoma-metric","kind":"idea","name":"Judge skin cancer AI by the thick melanomas it prevents, not the thin ones it finds","aka":[],"tldr":"Melanoma diagnoses have soared while deaths barely changed, a sign of overdiagnosis. AI skin apps should be judged on whether dangerous thick melanomas fall, not how many spots they flag.","summary":"Melanoma incidence has risen roughly six-fold in the US since 1975 with much smaller mortality change. AI dermatology tools risk amplifying detection of indolent in-situ lesions. Propose that regulatory and reimbursement evaluation of AI skin triage require thick (over 1 mm) melanoma incidence and biopsy-to-melanoma ratio as endpoints.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Overdiagnosis and false alarms): Welch & Black, Overdiagnosis in cancer (JNCI 2010)","url":"https://doi.org/10.1093/jnci/djq099"}],"tags":[],"related":[],"cancers":["melanoma"],"sections":["early-detection"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-overdiagnosis","b-ai-validation"],"keyPapers":["paper-welch-j-natl-cancer-inst"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"AI triage tools judged by detection volume increase in-situ diagnoses and biopsies without reducing thick melanoma incidence; tools optimised against thick-melanoma endpoints adopt more conservative operating points.","rationale":"The metric determines the algorithm's threshold.","test":"Cluster RCT of AI triage in primary care with three-year thick melanoma incidence and biopsy counts.","maturity":"speculative","actor":"regulator","cost":"medium","horizonYears":4},{"id":"idea-tr1-just-in-time-site-network","kind":"idea","name":"Just-in-time site activation: open a site in two weeks when a patient appears","aka":[],"tldr":"Instead of opening a trial at fifty hospitals and waiting for patients, keep a network of pre-vetted clinics ready and switch a trial on where a matching patient is found.","summary":"A network of community and academic sites holds master agreements, a central IRB, standing budgets and trained staff; when a matched patient is identified (via matching tools or referral), the site is activated for that protocol within 10-14 days. TAPUR and some rare-tumour and biomarker-defined trials have used this model; the idea is to make it the default for biomarker-selected phase 2 and rare-cancer trials and to fund the network as infrastructure.","asOf":"2026-09-08","links":[{"label":"ASCO TAPUR Study","url":"https://www.tapur.org/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["ai-trial-matching"],"targets":[],"drugs":[],"companies":[],"institutions":["asco"],"pathways":[],"terms":["basket-umbrella-platform"],"trials":[],"people":[],"bottlenecks":["b-trial-enrolment","b-rare-cancers"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Biomarker-selected trials run through a just-in-time network will reach target accrual in less than half the calendar time of conventional site selection and at lower cost per enrolled patient, because idle-site costs are removed.","rationale":"In conventional trials a large share of opened sites enrol zero or one patient, while eligible patients at non-participating sites are never enrolled. JIT inverts the logic: capacity follows the patient.","test":"Run two similar biomarker-selected phase 2 studies from one sponsor, one via JIT network and one via conventional site selection, and compare time to accrual, cost per patient and geographic spread of enrolled patients.","maturity":"early-clinical","actor":"industry","cost":"medium","horizonYears":2},{"id":"idea-bio1-ex-vivo-perfused-tumour","kind":"idea","name":"Keep a freshly removed tumour alive on a pump and test drugs in it","aka":[],"tldr":"After surgery, a tumour with its blood vessels can be connected to a pump and kept alive for hours or days, allowing drugs to be tested in genuinely human tissue.","summary":"Normothermic machine perfusion is standard in transplantation for livers and kidneys and can be applied to resected tumour-bearing specimens (for example liver segments containing metastases, or isolated limb specimens). Perfusion preserves vasculature and interstitial transport, so drug delivery, penetration and early pharmacodynamics can be measured in intact human tissue that no model reproduces.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Lab models that fail to predict what happens in patients): Wong, Siah & Lo, Estimation of clinical trial success rates (Biostatistics 2019)","url":"https://doi.org/10.1093/biostatistics/kxx069"}],"tags":[],"related":[],"cancers":["colorectal","hcc"],"sections":[],"technologies":["organoids","proteomics"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-preclinical-models"],"keyPapers":["paper-wong-biostatistics"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Perfused human tumour specimens remain viable and metabolically stable for at least 24 hours and show drug penetration and pharmacodynamic responses that differ measurably from matched organoid predictions.","rationale":"The transport barrier is the least well modelled part of drug action and cannot be measured in dissociated systems; the perfusion technology and surgical specimens both already exist.","test":"Feasibility study on 20 resected liver metastasis specimens: viability over 24 hours, imaging mass spectrometry of drug distribution, and comparison with organoid response from the same tumour.","maturity":"speculative","actor":"engineering","cost":"medium","horizonYears":5},{"id":"idea-bio2-pro-dormancy-therapy","kind":"idea","name":"Keep dormant cells asleep instead of trying to kill them","aka":[],"tldr":"If we cannot kill sleeping cancer cells, we could try to keep them asleep for life. That would turn residual cancer into a harmless passenger.","summary":"Dormancy is an active transcriptional programme involving NR2F1, SOX9, TGF-beta2 and retinoic acid signalling. Combination all-trans retinoic acid plus a hypomethylating agent restored NR2F1 and enforced dormancy in head and neck and breast models from the Aguirre-Ghiso group, and both drugs are approved and cheap. The clinical question is whether enforced dormancy is durable and tolerable for years.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Dormant cells and minimal residual disease): Tie et al., ctDNA analysis guiding adjuvant therapy in stage II colon cancer (NEJM 2022)","url":"https://doi.org/10.1056/NEJMoa2200075"}],"tags":[],"related":[],"cancers":["head-and-neck","breast-hr-positive","prostate"],"sections":[],"technologies":["epigenetic-drugs","mrd-testing"],"targets":[],"drugs":["azacitidine"],"companies":[],"institutions":[],"pathways":[],"terms":["late-recurrence","mrd"],"trials":[],"people":[],"bottlenecks":["b-dormancy-mrd","b-metastasis-biology"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Low-dose retinoid plus hypomethylating therapy in ctDNA-positive survivors keeps ctDNA stable or falling and delays radiographic relapse compared with observation, without cumulative toxicity.","rationale":"Prostate and breast cancers already prove that decades-long dormancy is a natural state, so the biology has an existence proof. Pro-dormancy is also a lower bar than eradication and may be achievable with well-characterised generic agents.","test":"A randomised phase 2 in ctDNA-positive survivors with ctDNA trajectory as primary endpoint, plus marrow NR2F1 staining as pharmacodynamic proof of mechanism.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":9},{"id":"idea-dormancy-maintenance-therapy","kind":"idea","name":"Keep them asleep: dormancy maintenance as adjuvant therapy","aka":[],"tldr":"Instead of trying to kill every hidden cancer cell after surgery, keep them dormant for life with low-toxicity drugs, the way extended hormone therapy already does in breast cancer.","summary":"This idea proposes dormancy maintenance as adjuvant therapy: keep hidden cancer cells dormant for life with low-toxicity drugs rather than trying to kill them all, as extended hormone therapy already does in breast cancer. Extended Endocrine therapy (SERMs, AIs, SERDs) and adjuvant CDK4/6 inhibitors may work partly by enforcing dormancy, and 5-azacytidine plus ATRA induced NR2F1 in a prostate pilot (Tumour dormancy pathway). The hypothesis is that a dormancy-enforcing regimen given for 3-5 years to patients positive for Minimal / molecular residual disease (MRD) delays or prevents relapse with less toxicity than cytotoxic escalation. The test is a randomised phase 2 in MRD-positive early Prostate cancer or HR-positive / HER2-negative breast cancer.","asOf":"2026-09-08","links":[{"label":"Sosa, Bragado and Aguirre-Ghiso, Mechanisms of disseminated cancer cell dormancy: an awakening field (Nature Reviews Cancer 2014)","url":"https://doi.org/10.1038/nrc3793"}],"tags":["mechanism","open-question"],"related":[],"cancers":["prostate","breast-hr-positive"],"sections":[],"technologies":["mrd-testing","endocrine-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":["mount-sinai","johns-hopkins"],"pathways":["tumor-dormancy","metastatic-cascade","er-signaling"],"terms":["mrd","late-recurrence"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-sosa-nat-rev-cancer"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A dormancy-enforcing regimen given for 3-5 years after curative therapy in MRD-positive patients delays or prevents relapse compared with observation, with less toxicity than cytotoxic escalation.","rationale":"Dormancy biology is now mechanistically defined; MRD assays identify who needs it; ER+ breast cancer shows the principle works clinically.","test":"Randomised phase 2 in MRD-positive early prostate or breast cancer: dormancy regimen vs observation, primary endpoint time to ctDNA/clinical relapse; embed DTC state biomarkers.","maturity":"early-clinical"},{"id":"idea-tr1-organ-impairment-pk-before-approval","kind":"idea","name":"Kidney and liver impairment dosing studies completed before approval, not years after","aka":[],"tldr":"Dosing advice for people with weak kidneys or liver is often missing at approval and added years later, if ever. Requiring those studies before approval would protect a large group of real-world patients from day one.","summary":"Regulators require dedicated or population-PK-based organ impairment dosing recommendations (mild, moderate and, where feasible, severe renal and hepatic impairment) as part of the initial marketing application for oncology drugs, rather than as post-marketing commitments, using sparse PK from broadened-eligibility trials and small dedicated cohorts. Ties to relaxing organ-function eligibility criteria.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Wrong doses): FDA Oncology Center of Excellence, Project Optimus","url":"https://www.fda.gov/about-fda/oncology-center-excellence/project-optimus"}],"tags":[],"related":[],"cancers":["multiple-myeloma","rcc","hcc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-dose-optimisation","b-aging-comorbidity","b-trial-enrolment"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Drugs approved with organ-impairment dosing will show lower toxicity-related hospitalisation among patients with impairment in real-world data than drugs approved without, and post-marketing commitments for these studies will fall.","rationale":"Organ impairment is common in cancer patients and clinicians either extrapolate or withhold drugs; post-marketing studies are frequently delayed or never completed.","test":"Audit completion times of organ-impairment post-marketing commitments for the last decade of oncology approvals; then require them pre-approval for three years and compare real-world outcomes in impaired patients.","maturity":"speculative","actor":"regulator","cost":"small","horizonYears":2},{"id":"idea-tr2-ctdna-futility-gates","kind":"idea","name":"Kill combination arms early using circulating tumour DNA, before waiting for scans","aka":[],"tldr":"A blood test at six weeks can show whether a treatment is doing anything. Trials should use it to drop failing combinations fast and move patients on.","summary":"Molecular response (ctDNA clearance or fall below a threshold at 6 to 9 weeks) correlates with progression-free and overall survival across several tumour types and drug classes. Platform trials could use pre-specified ctDNA futility rules at 20 patients per arm to stop non-performing combinations months earlier than radiological endpoints allow.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Too many combinations to test): Palmer & Sorger, Combination cancer therapy can confer benefit via patient-to-patient variability without drug additivity or synergy (Cell 2017)","url":"https://doi.org/10.1016/j.cell.2017.11.009"}],"tags":[],"related":["guardant-health","natera","idea-cd8-pet-io"],"cancers":[],"sections":[],"technologies":["liquid-biopsy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["ctdna","recist","pfs"],"trials":[],"people":[],"bottlenecks":["b-combination-space","b-trial-design"],"keyPapers":["paper-palmer-cell"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Arms stopped for ctDNA futility would, had they continued, have failed their radiological primary endpoint in at least 85% of cases; adopting the rule increases the number of arms tested per year by at least 50%.","rationale":"Several studies show early ctDNA dynamics predict RECIST response and survival on immunotherapy and targeted therapy. Futility, unlike efficacy, needs only a reliable negative predictor.","test":"Run the rule in shadow mode in an existing platform for two years, recording what would have been stopped and comparing with final radiological results.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":3},{"id":"idea-ferroptosis-persisters","kind":"idea","name":"Kill drug-tolerant persisters through ferroptosis","aka":[],"tldr":"The cells that survive targeted therapy change shape and become unusually dependent on an antioxidant enzyme, GPX4. Hitting them in that window might stop resistance before it evolves.","summary":"This idea proposes killing drug-tolerant persisters through ferroptosis: cells surviving targeted therapy become dependent on the antioxidant enzyme GPX4, so hitting them in that window might stop resistance. Persisters after EGFR, ALK or BRAF inhibition are mesenchymal and GPX4-dependent (Viswanathan and Hangauer, 2017); no drug-like GPX4 inhibitor exists, but xCT inhibitors and radiotherapy induce lipid peroxidation. The hypothesis is that a short ferroptosis-inducing pulse at maximal response eradicates persisters and prolongs progression-free survival, timed by the ctDNA nadir on Liquid biopsy (ctDNA). The test is a randomised phase 2 in EGFR-mutant Non-small-cell lung cancer of Osimertinib alone against Osimertinib plus consolidative SBRT / SABR or an xCT inhibitor at ctDNA nadir.","asOf":"2026-09-08","links":[{"label":"Hangauer et al., Drug-tolerant persister cancer cells are vulnerable to GPX4 inhibition (Nature 2017)","url":"https://doi.org/10.1038/nature24297"}],"tags":["mechanism","open-question"],"related":[],"cancers":["nsclc","melanoma"],"sections":[],"technologies":["sbrt","liquid-biopsy"],"targets":["egfr","alk","braf"],"drugs":["osimertinib"],"companies":[],"institutions":["broad-institute","stanford"],"pathways":["ferroptosis-cell-death","emt","clonal-evolution"],"terms":["resistance"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-hangauer-nature","paper-flaura-nejm-2018","paper-egfr-nsclc-lancet-oncol-2012","paper-egfr-nsclc-n-engl-j-med-2010"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A short ferroptosis-inducing pulse at the point of maximal response to a targeted agent eradicates persisters and prolongs progression-free survival compared with continuous targeted therapy alone.","rationale":"Persister GPX4 dependence is reproducible across models; the persister window is identifiable by ctDNA nadir; radiotherapy to residual lesions is a feasible ferroptosis inducer today.","test":"Randomised phase 2 in EGFR-mutant NSCLC: osimertinib alone vs osimertinib plus consolidative radiotherapy or an xCT inhibitor at ctDNA nadir; primary endpoint PFS; ferroptosis markers in on-treatment biopsies.","maturity":"preclinical-evidence"},{"id":"idea-bio1-persister-ferroptosis","kind":"idea","name":"Kill the sleeping survivor cells with iron-dependent cell death","aka":[],"tldr":"A few cancer cells survive treatment by going quiet rather than mutating. These survivors are unusually vulnerable to a particular kind of cell death, which a drug could trigger.","summary":"Drug-tolerant persister cells adopt a mesenchymal, slow-cycling state that depends on the lipid peroxidase GPX4; their elimination by GPX4 inhibition has been shown in several models across lung, breast and other cancers. Translating this requires a tolerable GPX4 inhibitor or an alternative ferroptosis inducer, and a schedule that applies it during the persister window shortly after maximal response.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Acquired resistance to every therapy): Soria et al., Osimertinib in untreated EGFR-mutated NSCLC (FLAURA, NEJM 2018)","url":"https://doi.org/10.1056/NEJMoa1713137"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["synthetic-lethality-approaches"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["resistance","mrd"],"trials":[],"people":[],"bottlenecks":["b-resistance","b-dormancy-mrd"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Ferroptosis induction timed to the persister window after maximal response to targeted therapy reduces residual disease and delays regrowth in vivo compared with continued targeted therapy alone.","rationale":"Persisters are the reservoir from which genetic resistance later emerges; eliminating them attacks resistance before mutations arise, and the vulnerability is a state rather than a genotype, so it applies across drivers.","test":"In vivo studies in three driver-defined models comparing scheduled ferroptosis induction at nadir with continuous therapy, measuring residual cell number and time to regrowth.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":6},{"id":"idea-tr2-biomarker-evidence-grading","kind":"idea","name":"Label every biomarker claim with an evidence phase, like drugs","aka":[],"tldr":"Drugs are labelled phase 1, 2 or 3 so everyone knows how proven they are. Biomarkers should carry a comparable grade, from B1 discovery to B5 utility shown in a randomised trial, so that a marker with only discovery-stage evidence is not mistaken for a validated one in guidelines and papers.","summary":"Biomarker development stages exist in the literature (discovery, analytical validation, clinical validation, clinical utility, as in the Early Detection Research Network's five phases) but are not applied to published claims or guideline statements. A simple grading (B1 discovery, B2 analytically validated, B3 clinically validated retrospectively, B4 prospectively validated, B5 utility shown in a randomised trial) attached to biomarker entries in guidelines, knowledge bases and papers would make the evidence gap visible.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Biomarkers are not validated or standardised): Fernandez et al., Examination of low ERBB2 protein expression in breast cancer tissue (JAMA Oncology 2022)","url":"https://doi.org/10.1001/jamaoncol.2021.7239"}],"tags":[],"related":["oncokb","civic","esmo-guidelines","nccn"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-biomarker-validation","b-knowledge-diffusion"],"keyPapers":["paper-fernandez-jama-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"After adoption, the proportion of guideline-recommended biomarkers at B4 or above will be reported and will rise year on year, and clinicians will rate biomarker evidence more accurately in surveys.","rationale":"Evidence grading (GRADE, levels of evidence) improved clarity for treatments; biomarkers lack any equivalent that patients and clinicians see.","test":"Grade all biomarkers in two guideline sets and one knowledge base; survey clinicians before and after on their perception of validation status.","maturity":"speculative","actor":"research","cost":"small","horizonYears":2},{"id":"idea-bio1-truncal-branch-labelling","kind":"idea","name":"Label every targetable mutation as truncal or branch on the report","aka":[],"tldr":"A drug aimed at a mutation present in every tumour cell works differently from one aimed at a mutation in only some cells. Test reports should say which is which.","summary":"Tumour sequencing reports list alterations without their cancer cell fraction. Adding a clonality estimate (truncal, subclonal with estimated fraction, indeterminate) is computationally routine from purity- and copy-number-adjusted VAFs. Trials could then stratify by clonality and drug labels could state that benefit was shown for clonal alterations.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Tumour heterogeneity and clonal evolution): Gerlinger et al., Intratumor heterogeneity and branched evolution (NEJM 2012)","url":"https://doi.org/10.1056/NEJMoa1113205"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["cgp"],"targets":[],"drugs":[],"companies":["foundation-medicine","tempus","guardant-health"],"institutions":[],"pathways":[],"terms":["vaf","ngs"],"trials":[],"people":[],"bottlenecks":["b-tumor-heterogeneity","b-biomarker-validation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Patients whose targetable alteration is subclonal have materially shorter progression-free survival on the matched drug than those with a clonal alteration, and reporting clonality shifts prescribing toward combinations in the subclonal group.","rationale":"Subclonal targets predict poor responses in lung, colorectal and breast cohorts; the field ignores this because reports do not surface it. It costs nothing to compute.","test":"Re-analyse the sequencing from three completed targeted-therapy trials to estimate the clonal versus subclonal hazard ratio; if confirmed, pilot clonality labelling with two commercial panel providers and audit prescribing changes.","maturity":"preclinical-evidence","actor":"data","cost":"small","horizonYears":2},{"id":"idea-fund-mcbs-linked-pricing","kind":"idea","name":"Launch prices indexed to the ESMO benefit scale, revisited when survival matures","aka":[],"tldr":"Pay more for drugs that clearly help people live longer or better, and less for those that barely move the needle, using a public benefit scale doctors already use.","summary":"National payers adopt a rule that reimbursed price at launch is tied to the ESMO Magnitude of Clinical Benefit Scale (or ASCO Value Framework) grade of the pivotal evidence, with a mandatory renegotiation when overall survival or quality-of-life data mature. Grade 4 to 5 (or A to B in curative settings) commands a premium band; grade 1 to 2 is reimbursed only at or near the price of the comparator. Several European payers already consult the scale informally; making the link explicit and automatic changes the return calculus for marginal drugs before they enter development.","asOf":"2026-09-08","links":[{"label":"ESMO Magnitude of Clinical Benefit Scale","url":"https://www.esmo.org/guidelines/esmo-mcbs"}],"tags":[],"related":["idea-fund-value-based-patent-extension","idea-fund-pay-for-cure-annuities"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["esmo","asco"],"pathways":[],"terms":["os","pfs"],"trials":[],"people":[],"bottlenecks":["b-incentive-misalignment","b-drug-pricing"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Explicit MCBS-indexed pricing across a group of countries lowers the average launch price of low-benefit oncology drugs by at least 30% and, within eight years, increases the proportion of pivotal trials designed to achieve high MCBS grades (overall survival, quality of life endpoints).","rationale":"Value-based frameworks exist and are validated but have no teeth; where price is linked to benefit (Germany's AMNOG added-benefit assessment, France's ASMR rating) evidence of a shift in development priorities has been reported. Oncology has the best-developed benefit scales of any specialty.","test":"A payer coalition applies the rule to all new oncology reimbursements for three years and compares launch prices and pivotal trial designs of subsequent filings with a control set of countries.","maturity":"speculative","actor":"payer","cost":"small","horizonYears":3},{"id":"idea-tr1-lay-trial-navigators","kind":"idea","name":"Lay trial navigators funded per centre, evaluated in a randomised trial","aka":[],"tldr":"A trained non-clinical guide who explains trials, arranges logistics and keeps in touch could make the difference between a patient hearing about a trial and actually joining one.","summary":"Fund one lay navigator per 300 new cancer patients at community and safety-net hospitals, with a defined role: identify potentially eligible patients from matching tools, explain trials in plain language, coordinate screening logistics and follow up. Patient navigation improves timeliness of cancer care; the specific effect on trial enrolment has small positive studies and deserves a definitive randomised test.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Trials enrol too few, too slowly): Unger et al., Systematic review of barriers to cancer trial participation (JNCI 2019)","url":"https://doi.org/10.1093/jnci/djy221"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["nci","asco"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-enrolment","b-trial-diversity"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Patients randomised to a navigator will have at least a 50 percent higher trial enrolment rate than usual care, with the largest effect in minority and low-income patients.","rationale":"Enrolment fails on logistics and trust more than on eligibility. Navigators address both and are far cheaper than clinical staff.","test":"Individually randomised trial at six hospitals, 3,000 newly diagnosed patients, primary outcome enrolment in any interventional trial within 12 months.","maturity":"early-clinical","actor":"philanthropy","cost":"medium","horizonYears":2},{"id":"idea-tr1-age-floor-twelve-for-adult-trials","kind":"idea","name":"Let adolescents from age 12 into adult trials when the cancer biology is the same","aka":[],"tldr":"Teenagers with cancers that are really adult cancers, like melanoma or sarcoma, are barred from adult trials by an age line at 18. Letting them in from age 12, where biology and dosing allow, would give them access years earlier.","summary":"Adult oncology trials in histologies that occur in adolescents (melanoma, sarcomas, Hodgkin lymphoma, germ cell tumours, colorectal in Lynch syndrome) set the minimum age at 12 with weight-based dosing where required and paediatric assent, as FDA guidance permits. Sponsors would need to justify an age floor above 12 in these histologies.","asOf":"2026-09-08","links":[{"label":"FDA: Eligibility Criteria: Minimum Age Considerations for Inclusion of Pediatric Patients","url":"https://www.fda.gov/regulatory-information/search-fda-guidance-documents/cancer-clinical-trial-eligibility-criteria-minimum-age-considerations-inclusion-pediatric-patients"}],"tags":[],"related":[],"cancers":["melanoma","sarcoma","hodgkin-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-diversity","b-rare-cancers"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Lowering the age floor will enrol adolescents into adult trials at a rate proportional to incidence and shorten the delay between adult and paediatric label extensions from years to months for those histologies.","rationale":"Adolescents fall between paediatric and adult trial systems; the FDA has stated that age 12 is appropriate when biology and PK support it. Paediatric label delays of several years are common.","test":"Compare adolescent enrolment and time to paediatric labelling for agents in trials adopting a 12-year floor versus historical 18-year floors in the same histologies.","maturity":"early-clinical","actor":"regulator","cost":"small","horizonYears":2},{"id":"idea-prev-cascade-direct-contact-relatives","kind":"idea","name":"Let clinics contact relatives directly when a cancer gene is found","aka":[],"tldr":"When someone tests positive for a BRCA or Lynch mutation, relatives are told only if the patient passes the message on. Most do not. Letting clinics contact relatives directly, with consent, could double testing.","summary":"Cascade testing uptake is 20-40%. Trials of health-system-initiated direct contact (with proband consent) in the Netherlands and Australia show higher uptake. Propose direct contact as the default, with digital family letters, telegenetic counselling, and free mail-in testing for relatives regardless of their insurer.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Inherited risk is mostly unidentified): Childers et al., National estimates of genetic testing in women with breast or ovarian cancer (JCO 2017)","url":"https://doi.org/10.1200/JCO.2017.73.6314"}],"tags":[],"related":[],"cancers":[],"sections":["prevention"],"technologies":["germline-testing"],"targets":["brca"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["germline-vs-somatic"],"trials":[],"people":[],"bottlenecks":["b-hereditary-risk"],"keyPapers":["paper-childers-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Direct contact doubles cascade testing uptake in first-degree relatives within 12 months.","rationale":"The proband-mediated model fails because of family dynamics and low health literacy; direct contact is standard in other public health settings such as contact tracing.","test":"RCT of direct versus proband-mediated contact across five genetics services.","maturity":"early-clinical","actor":"clinic","cost":"small","horizonYears":2},{"id":"idea-prev-mced-stage-endpoint-surrogate","kind":"idea","name":"Let MCED trials read out on late-stage incidence, with mortality follow-up mandated","aka":[],"tldr":"Multi-cancer early detection blood tests take a decade to prove they save lives. Regulators could accept a fall in late-stage cancers as the first answer, validated against pooled data from completed screening trials, provided approval is conditional on continued mortality follow-up.","summary":"NHS-Galleri chose stage III/IV incidence as its primary endpoint; regulators have not said whether that suffices for approval or coverage. Propose a formal surrogate-validation exercise pooling individual data from completed screening RCTs (NLST, NELSON, UKCTOCS, ERSPC, Minnesota, NordICC) to estimate the trial-level correlation between late-stage incidence reduction and cancer-specific mortality reduction, and a conditional-approval pathway with mandated mortality follow-up.","asOf":"2026-09-08","links":[{"label":"NHS-Galleri trial","url":"https://www.nhs-galleri.org"},{"label":"CISNET","url":"https://cisnet.cancer.gov"}],"tags":[],"related":[],"cancers":[],"sections":["early-detection"],"technologies":["mced","liquid-biopsy"],"targets":[],"drugs":["galleri"],"companies":[],"institutions":[],"pathways":[],"terms":["stage-shift","os"],"trials":["nhs-galleri","pathfinder-2"],"people":[],"bottlenecks":["b-early-detection","b-trial-design"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Across historical screening RCTs, the trial-level relative reduction in stage III/IV incidence predicts cancer-specific mortality reduction well enough (R-squared above 0.7) that a pre-specified late-stage incidence threshold can serve as a conditional endpoint.","rationale":"UKCTOCS is the cautionary case: it shifted stage without reducing mortality because the ovarian cancers that shifted were still lethal. A pooled analysis would quantify when stage shift does and does not translate, per cancer, instead of arguing by anecdote.","test":"Individual-patient-data meta-analysis of screening RCTs (two years, small budget); then FDA/MHRA guidance on conditional MCED approval; NHS-Galleri and the NCI Vanguard study as first users.","maturity":"speculative","actor":"regulator","cost":"small","horizonYears":3},{"id":"idea-reg-third-party-label-update","kind":"idea","name":"Let non-profits and academics add a cancer indication to an off-patent drug's label","aka":[],"tldr":"Only the manufacturer can ask regulators to add a new use to a drug's label, and generic makers have no reason to. Universities and charities should be allowed to apply.","summary":"When a publicly funded trial proves an old drug works in cancer, the result rarely reaches the label because no marketing authorisation holder will file, leaving the indication off-label with weak reimbursement and guideline status. The EU's 2023 pharmaceutical reform proposal includes a mechanism for non-commercial entities to submit evidence for a new indication, which the regulator can then require all holders to include; the FDA has no equivalent. The proposal is a formal third-party supplement pathway in FDA, EMA and other regulators, with fee waivers, allowing academic sponsors to file, and a label change binding on all generic versions.","asOf":"2026-09-08","links":[{"label":"EU pharmaceutical legislation reform","url":"https://health.ec.europa.eu/medicinal-products/pharmaceutical-strategy-europe/reform-eu-pharmaceutical-legislation_en"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-generic-repurposing","b-regulatory-fragmentation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Within five years of the pathway opening, at least five off-patent drugs gain oncology indications through third-party filings, and reimbursement and guideline adoption of those indications follow within a year of labelling.","rationale":"The label is the hinge on which reimbursement, guidelines and prescribing turn; a pathway that decouples label updates from the commercial interest of the holder removes the last barrier for proven repurposed drugs.","test":"Pass the EU provision and pilot an FDA equivalent; file the first two academic supplements (for example a positive repurposing trial result) and measure time to label change and downstream reimbursement.","maturity":"early-clinical","actor":"regulator","cost":"small","horizonYears":4},{"id":"idea-bio2-patient-partnered-rare-commons","kind":"idea","name":"Let patients themselves donate their records and samples for ultra-rare cancers","aka":[],"tldr":"Patients with ultra-rare cancers are scattered across countries, beyond any single hospital's reach. Patient-driven projects that recruit online, post saliva and tumour sample kits and release data openly have already produced genomic findings in angiosarcoma; sustainability and international consent rules are the open problems.","summary":"Patient-partnered research projects have assembled cohorts in angiosarcoma, metastatic breast cancer and other diseases by direct online recruitment, mailed sample kits, and consent for medical record retrieval and open data release. The model reaches patients that no single hospital can, and produced genomic findings in diseases previously too rare to study. Sustainability and international consent harmonisation are the open problems.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Rare and paediatric cancers without markets): Gatta et al., Rare cancers are not so rare: the rare cancer burden in Europe (EJC 2011)","url":"https://doi.org/10.1016/j.ejca.2011.08.008"}],"tags":[],"related":["cbioportal","genie","cancer-models"],"cancers":["sarcoma"],"sections":[],"technologies":["wes-wgs"],"targets":[],"drugs":[],"companies":[],"institutions":["broad-institute","dana-farber"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-rare-cancers","b-data-silos","b-patient-voice"],"keyPapers":["paper-gatta-eur-j-cancer"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Patient-partnered recruitment assembles cohorts of over 200 patients in cancers with fewer than 500 annual cases per country within two years, at a cost per case below conventional biobanking.","rationale":"Direct-to-patient recruitment removes site-by-site activation, the dominant cost and delay in rare disease research. Openly released data attract analysts who would never have obtained the samples themselves.","test":"Launch one disease-specific patient-partnered project with pre-registered targets on enrolment, sample return rate, record retrieval success and time to first public data release.","maturity":"being-tested-at-scale","actor":"patients","cost":"medium","horizonYears":4},{"id":"idea-tr2-bandit-allocation","kind":"idea","name":"Let the trial learn: response-adaptive allocation across many combination arms","aka":[],"tldr":"As results come in, the trial sends more new patients to the arms that are working and fewer to those that are not, so more people benefit and bad arms die faster.","summary":"Multi-armed bandit and Bayesian response-adaptive randomisation, used in I-SPY 2 and in the REMAP-CAP platform during COVID-19, allocate patients towards the arms that are performing best while maintaining control of false positives. With ten or more combination arms, adaptive allocation shortens time to identify winners and reduces the number of patients on futile arms. Regulators accept these designs with pre-specified simulation of operating characteristics.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Too many combinations to test): Palmer & Sorger, Combination cancer therapy can confer benefit via patient-to-patient variability without drug additivity or synergy (Cell 2017)","url":"https://doi.org/10.1016/j.cell.2017.11.009"}],"tags":[],"related":["idea-tr2-neoadjuvant-combo-platform","idea-tr2-ctdna-futility-gates"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["basket-umbrella-platform","pcr"],"trials":[],"people":[],"bottlenecks":["b-combination-space","b-trial-design"],"keyPapers":["paper-palmer-cell"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Adaptive allocation across ten combination arms identifies the best arm with 30% fewer patients than equal randomisation at the same error rates, in simulation and in a live platform.","rationale":"REMAP-CAP found effective COVID-19 treatments faster than fixed designs. Oncology platforms have been slower to adopt because of endpoint latency; ctDNA or pathological response as intermediate endpoints removes that obstacle.","test":"Implement in a neoadjuvant platform using pathological response as the adaptive endpoint; compare patients-to-decision with a fixed-randomisation shadow analysis.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":4},{"id":"idea-reg-secondary-patent-thicket-limits","kind":"idea","name":"Limit secondary patents and pay-for-delay so cancer generics arrive on time","aka":[],"tldr":"Companies extend monopolies on cancer drugs with dozens of minor patents and deals that pay generic makers to stay out. Closing these loopholes would bring cheaper versions years earlier.","summary":"Analyses of imatinib, lenalidomide and other oncology blockbusters show effective exclusivity extended by years through secondary patents on salts, formulations and dosing and through settlements delaying generic entry. India's Section 3(d) restricts secondary patents; the EU and US have sanctioned some pay-for-delay deals. The proposal is a coordinated set of reforms: a higher inventive-step bar for secondary pharmaceutical patents, presumptive illegality of reverse-payment settlements, and a public database of patent expiry dates per oncology product so generic entry can be planned.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Prices and value): Prasad, De Jesús & Mailankody, The high price of anticancer drugs: origins, implications, barriers, solutions (Nat Rev Clin Oncol 2017)","url":"https://doi.org/10.1038/nrclinonc.2017.31"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":["imatinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-drug-pricing","b-ip-collaboration"],"keyPapers":["paper-prasad-nat-rev-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Reforms reduce the gap between compound patent expiry and first generic entry for oncology drugs from a median of several years to under one year, and reduce spend on affected drugs by more than half within two years of entry.","rationale":"Generic entry produces the largest price fall available in pharmaceuticals (often over 80%) and delays to entry are among the most expensive policy failures per dollar; the legal tools exist and have been shown to work in some jurisdictions.","test":"Quantify effective exclusivity extension for the 30 highest-spend oncology drugs across five jurisdictions, then track generic entry timing following reform in one jurisdiction.","maturity":"early-clinical","actor":"policy","cost":"small","horizonYears":5},{"id":"idea-nl-bariatric-cancer-registry-linkage","kind":"idea","name":"Link bariatric and GLP-1 registries to cancer registries in every country that has both","aka":[],"tldr":"Millions of people have had weight-loss surgery or now take weight-loss drugs. Linking those records to cancer registries would show, cancer by cancer, how much reversing obesity prevents, for almost no cost.","summary":"Nordic registries and the Cleveland Clinic SPLENDID cohort show about a third fewer obesity-related cancers after bariatric surgery, but individual sites (oesophageal adenocarcinoma, colorectal, pancreatic) are underpowered, and the emerging GLP-1 receptor agonist data are from insurance claims with short follow-up. Most high-income countries have national bariatric surgery registries, complete cancer registries and prescription databases; a federated linkage with a common protocol would produce site-specific, sex-specific estimates, detect any unexpected harm (post-bariatric colorectal cancer, thyroid), and provide the counterfactual against which GLP-1 drugs can be judged.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Weak real-world evidence and registries): Gyawali, Hey & Kesselheim, Assessment of the clinical benefit of cancer drugs receiving accelerated approval (JAMA Intern Med 2019)","url":"https://doi.org/10.1001/jamainternmed.2019.0462"}],"tags":[],"related":["idea-prev-glp1-cancer-prevention-rct"],"cancers":["endometrial","colorectal","esophageal","hcc","pancreatic","rcc"],"sections":["nutrition-lifestyle","prevention"],"technologies":["bariatric-surgery-cancer-incidence","glp1-agonists-cancer-risk"],"targets":[],"drugs":[],"companies":[],"institutions":["karolinska","cleveland-clinic"],"pathways":[],"terms":["obesity-related-cancers","real-world-evidence"],"trials":[],"people":[],"bottlenecks":["b-real-world-evidence","b-data-silos","b-prevention-adoption"],"keyPapers":["paper-gyawali-jama-intern-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Federated linkage across at least five countries will show site-specific reductions in cancer incidence after bariatric surgery that scale with weight loss maintained at five years, and GLP-1 receptor agonist users will show a similar gradient by cumulative exposure.","rationale":"The exposure is common, the outcome registries exist, the analytic methods (target trial emulation) are mature, and randomised trials with cancer endpoints are a decade away. The data would inform both prevention policy and the design of any GLP-1 cancer trial.","test":"Common-protocol federated analysis (Sweden, Denmark, Finland, Scotland, Ontario, Israel) of bariatric surgery and GLP-1 receptor agonist exposure vs matched obese controls with cancer incidence by site as outcome; pre-registered, with results published within three years.","maturity":"early-clinical","actor":"data","cost":"small","horizonYears":3},{"id":"idea-data-registry-genomics-linkage-programme","kind":"idea","name":"Link every national cancer registry to tumour genomics","aka":[],"tldr":"Join the national list of who got cancer to the genetic profile of each tumour, so we can see for the whole population which mutations matter and which drugs work for them.","summary":"Genomics England linked to the English cancer registry, and Nordic biobanks linked to registries, show the power of population-scale genomics with outcomes. Most countries with registries have no such linkage; genomic data sit in labs. The proposal funds registry-genomics linkage in every country with a population registry, using privacy-preserving tokens and structured genomic deposit, with governed access for real-world studies of biomarker-defined populations.","asOf":"2026-09-08","links":[{"label":"Genomics England","url":"https://www.genomicsengland.co.uk/"}],"tags":[],"related":["seer","genie","idea-data-structured-genomic-reports"],"cancers":[],"sections":["ai-computation"],"technologies":["ngs","wes-wgs"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-real-world-evidence","b-data-silos","b-rare-cancers"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Population-scale registry-genomics linkage will allow outcome analyses of biomarker-defined groups with fewer than 1 percent prevalence (for example, NRG1 fusions, rare KRAS alleles) within two years, which no trial or single-centre cohort can achieve.","rationale":"Rare-biomarker questions are exactly where randomised trials are infeasible; population registries are the only source of unbiased denominators.","test":"Link one national registry to structured genomic data from its major labs; publish outcome analyses for three rare biomarker-defined groups.","maturity":"being-tested-at-scale","actor":"data","cost":"large","horizonYears":4},{"id":"idea-data-atlas-to-outcome-linkage","kind":"idea","name":"Link single-cell and spatial tumour atlases to clinical outcomes","aka":[],"tldr":"The detailed molecular maps of tumours being built today mostly lack information on what happened to the patient. Require every atlas sample to carry consented outcome data.","summary":"The Human Tumor Atlas Network and similar single-cell and spatial efforts produce rich molecular maps, but clinical annotation is thin and outcome follow-up rare. The proposal requires atlas funding to include consent for registry linkage and a minimum clinical data set (mCODE), with outcome updates pushed annually, so that cell states discovered can be tested as prognostic and predictive markers without new cohorts.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Data silos): AACR Project GENIE","url":"https://www.aacr.org/professionals/research/aacr-project-genie/"}],"tags":[],"related":["cellxgene-hca","tcga-gdc","cptac"],"cancers":[],"sections":["ai-computation"],"technologies":["single-cell-spatial"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-data-silos","b-biomarker-validation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Outcome-linked atlases will produce at least twice as many validated prognostic cell-state markers per dollar as unlinked atlases.","rationale":"TCGA's value came largely from its clinical annotation and follow-up; single-cell atlases have repeated the molecular depth without the clinical linkage.","test":"Add registry linkage to one existing atlas cohort retrospectively; count the number of cell-state associations with survival that can be tested and how many replicate in an independent cohort.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":3},{"id":"idea-bio1-multi-organ-chip-tox","kind":"idea","name":"Linked human organ chips to predict side effects before people are dosed","aka":[],"tldr":"Damage to the lungs, heart or liver is a common reason cancer drugs fail. Connected chips of human tissue may spot this earlier than animal tests.","summary":"Interstitial lung disease with ADCs, cardiotoxicity with HER2 agents and hepatotoxicity with several classes are poorly predicted by rodents. Coupled microphysiological systems with human lung, heart, liver and kidney compartments and shared circulation can measure organ-specific injury from a candidate at clinically relevant exposures. US legislation now allows non-animal methods to support investigational new drug applications, giving a regulatory route.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Lab models that fail to predict what happens in patients): Wong, Siah & Lo, Estimation of clinical trial success rates (Biostatistics 2019)","url":"https://doi.org/10.1093/biostatistics/kxx069"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["adc","organoids"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["ild","payload"],"trials":[],"people":[],"bottlenecks":["b-preclinical-models","b-toxicity-qol"],"keyPapers":["paper-wong-biostatistics"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A multi-organ chip panel correctly identifies the organ of clinical dose-limiting toxicity for the majority of a retrospective set of ADCs with known human toxicity profiles.","rationale":"ADC toxicity is frequently payload- and off-target-driven in human-specific ways; the chips are human by construction, and the retrospective validation set already exists.","test":"Blinded retrospective study across 15 ADCs and kinase inhibitors with known clinical toxicity, scoring organ prediction accuracy against animal study predictions.","maturity":"preclinical-evidence","actor":"engineering","cost":"medium","horizonYears":4},{"id":"idea-data-linked-pharmacovigilance-interactions","kind":"idea","name":"Linked prescribing and outcome data to find drug interactions with cancer therapy","aka":[],"tldr":"Use joined-up pharmacy and hospital records to spot when a common everyday medicine makes a cancer drug work worse or cause more harm.","summary":"Interactions between anticancer agents and common co-medications (proton pump inhibitors with some kinase inhibitors and capecitabine; antibiotics and steroids with immunotherapy) have emerged from retrospective analyses years after approval. The proposal is a standing surveillance system using linked prescribing and outcome data that screens all new oncology drugs against the 200 most common co-medications, with signals triaged to confirmatory analysis or trials.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Weak real-world evidence and registries): Gyawali, Hey & Kesselheim, Assessment of the clinical benefit of cancer drugs receiving accelerated approval (JAMA Intern Med 2019)","url":"https://doi.org/10.1001/jamainternmed.2019.0462"}],"tags":[],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["real-world-evidence"],"trials":[],"people":[],"bottlenecks":["b-real-world-evidence","b-toxicity-qol"],"keyPapers":["paper-gyawali-jama-intern-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Systematic screening will detect clinically relevant interactions for new drugs within 18 months of approval, compared with a historical median of several years.","rationale":"The PPI and capecitabine signal and the antibiotic and immunotherapy signal were both found in retrospective trial and registry analyses; a systematic screen would have found them sooner.","test":"Run the screen on five drugs approved three or more years ago; check whether it rediscovers known interactions and how many new signals it produces; validate the top signals in independent data.","maturity":"early-clinical","actor":"data","cost":"small","horizonYears":2},{"id":"idea-tr2-material-failure-disclosure","kind":"idea","name":"Listed companies must disclose top-line data, not just 'did not meet endpoint'","aka":[],"tldr":"When a public company announces a trial failure, it should be required to give the actual numbers, as it must for a success.","summary":"Securities regulators require disclosure of material events, and trial failures are material. Yet failure announcements typically omit effect sizes, confidence intervals and safety, which are routinely disclosed for successes. A securities-regulation rule that material trial announcements include a standard minimum data set (primary endpoint estimate with interval, key secondaries, serious adverse events) would put the numbers in the public record within days rather than years.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Failures are hidden): Anderson et al., Compliance with results reporting at ClinicalTrials.gov (NEJM 2015)","url":"https://doi.org/10.1056/NEJMsa1409364"}],"tags":[],"related":["idea-tr2-termination-reports"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-negative-results","b-incentive-misalignment"],"keyPapers":["paper-anderson-n-engl-j-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"After the rule, the median time from a phase 3 oncology failure to public availability of the primary effect estimate falls from over a year to under one month.","rationale":"Investors and clinicians share an interest in the numbers; the asymmetry between success and failure disclosures is a choice, not a necessity. Existing rules on balanced disclosure provide a legal hook.","test":"Audit the last five years of oncology failure announcements for data content; propose a standard; pilot voluntary adoption with an industry body and measure uptake.","maturity":"speculative","actor":"policy","cost":"small","horizonYears":2},{"id":"idea-acc-guideline-concordance-dashboards","kind":"idea","name":"Live guideline-concordance dashboards for every tumour board, generated from the record","aka":[],"tldr":"Hospitals rarely know what fraction of their patients got the recommended treatment. Software reading the electronic record can show each team, every month, where care deviated from guidelines.","summary":"Guideline adherence differs from hospital to hospital and is usually measured years later by registry studies. Structured oncology data (mCODE-style) and rule engines encoding guideline pathways make near-real-time concordance measurement possible. Each multidisciplinary team would see its own concordance by tumour type and stage, with justified deviations flagged separately from unjustified ones, and could compare against peers.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Fragmented care and guideline gaps): Hanna et al., Mortality due to cancer treatment delay: systematic review and meta-analysis (BMJ 2020)","url":"https://doi.org/10.1136/bmj.m4087"}],"tags":[],"related":["nccn","esmo-guidelines"],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-care-fragmentation","b-knowledge-diffusion","b-data-silos"],"keyPapers":["paper-hanna-bmj"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Teams receiving monthly concordance feedback will increase guideline-concordant treatment by at least ten percentage points within a year, with the largest gains in centres starting below the median.","rationale":"Audit and feedback is among the best-evidenced quality interventions in medicine; the barrier in oncology has been the labour of abstraction, which structured data removes.","test":"A cluster-randomised trial of dashboards across 40 hospitals with registry-verified concordance and survival as endpoints.","maturity":"early-clinical","actor":"data","cost":"medium","horizonYears":3},{"id":"idea-reg-approval-access-lag-tracker","kind":"idea","name":"Live tracker of the lag from first approval to real availability in every country","aka":[],"tldr":"A drug approved in the US may take five years to reach a patient in Poland or never reach Nigeria. A live public tracker would show exactly where and why it is stuck.","summary":"EFPIA's W.A.I.T. indicator covers Europe annually; nothing comparable exists for Asia, Latin America or Africa, and none tracks the steps between approval and reimbursed availability. The proposal is an automated, open tracker that ingests regulatory decisions, HTA outcomes and reimbursement lists for every oncology drug in at least 60 countries and shows the stage at which each drug is stalled: not filed, under review, approved but not reimbursed, reimbursed with restrictions.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Regulatory divergence between regions): FDA Oncology Center of Excellence, Project Orbis","url":"https://www.fda.gov/about-fda/oncology-center-excellence/project-orbis"}],"tags":[],"related":["fda-approvals","clinicaltrials-gov"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-regulatory-fragmentation","b-global-access"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Countries whose lag data are published see faster median approval-to-reimbursement intervals within three years, and sponsors file earlier in countries shown to be 'not filed' outliers.","rationale":"Non-filing by sponsors, not slow regulators, is the main cause of unavailability in many middle-income countries; attributing delay correctly directs pressure to the right party.","test":"Prototype the tracker for 30 oncology drugs in 40 countries using public sources, validate against manual audits, and publish; measure filing behaviour over the following two years.","maturity":"speculative","actor":"data","cost":"small","horizonYears":2},{"id":"idea-data-computable-living-guidelines","kind":"idea","name":"Living guidelines published as versioned, computable rules","aka":[],"tldr":"Cancer treatment guidelines would be updated continuously and published in a form computers can read, so hospital systems, apps and decision tools update themselves the day the evidence changes.","summary":"Guidelines are PDFs updated annually or less; software that encodes them lags further. The proposal is for major guideline bodies (NCCN, ESMO, ASCO, national bodies) to publish recommendations as structured, versioned data (HL7 Clinical Practice Guidelines on FHIR, with explicit population, intervention, evidence grade and citation), updated within weeks of practice-changing evidence, with a public change log. The Australian living stroke and COVID guidelines and MAGICapp show living, structured guidance is feasible.","asOf":"2026-09-08","links":[{"label":"HL7 CPG-on-FHIR","url":"https://hl7.org/fhir/uv/cpg/"},{"label":"MAGICapp","url":"https://magicevidence.org/"}],"tags":[],"related":["nccn-org","esmo-guidelines"],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["nccn","esmo","asco"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-knowledge-diffusion"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Computable living guidelines will cut the median time from practice-changing publication to updated recommendation from more than a year to under 60 days, and downstream decision support will update within a further 30 days.","rationale":"Living guidelines have been maintained for stroke and COVID-19 for years; the machine-readable layer is what allows the update to propagate to the point of care rather than stopping at a website.","test":"One guideline body publishes one disease (for example metastatic NSCLC) as computable living guidance for two years; measure update latency and the number of software systems consuming the feed.","maturity":"early-clinical","actor":"policy","cost":"medium","horizonYears":3},{"id":"idea-moon-living-plain-evidence-summaries","kind":"idea","name":"Living plain-language evidence summaries for every common cancer question in 20 languages","aka":[],"tldr":"For each question patients actually ask, keep a short, current, sourced answer in plain words, updated as evidence changes and available in the languages people speak.","summary":"Trustworthy information exists (NCI PDQ, Cancer Research UK, Cochrane plain summaries) but is fragmented, slow to update and mostly English. The proposal is a living library: a defined set of the several thousand most-asked questions, each with a plain answer drafted with language-model assistance from guidelines and systematic reviews, reviewed and signed by named experts, versioned, translated and re-checked on a schedule, with open licensing so clinics, platforms and assistants can embed it.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Misinformation and unproven therapies): Johnson et al., Cancer misinformation and harmful information on Facebook and other social media (JNCI 2022)","url":"https://doi.org/10.1093/jnci/djab141"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["nci","cruk"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-misinformation","b-knowledge-diffusion"],"keyPapers":["paper-johnson-j-natl-cancer-inst"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"The library becomes the most-cited source in assistant answers and platform labels for cancer questions and reduces measured misinformation belief in populations exposed to it.","rationale":"Misinformation fills the vacuum left by absent, outdated or unreadable good information; the marginal cost of maintaining answers has fallen with drafting tools while expert review keeps quality.","test":"Build 1,000 questions in five languages; measure usage, citation in assistant outputs, and knowledge in surveyed patients versus controls.","maturity":"early-clinical","actor":"data","cost":"medium","horizonYears":2},{"id":"idea-tr2-preclinical-living-reviews","kind":"idea","name":"Living systematic reviews of animal and organoid evidence before every new trial","aka":[],"tldr":"Before testing a drug in people, someone should systematically gather all the animal and laboratory evidence, including the studies that failed. Almost no cancer trial does this.","summary":"CAMARADES and the SYRCLE group have shown that systematic review and meta-analysis of preclinical studies reveals publication bias, small-study effects and true effect sizes far below those in the headline papers. Requiring a registered, continuously updated systematic review of preclinical evidence (with automated literature surveillance) as part of any trial protocol or ethics application would ground trial decisions in the whole evidence base.","asOf":"2026-09-08","links":[{"label":"CAMARADES","url":"https://www.ed.ac.uk/clinical-brain-sciences/research/camarades"}],"tags":[],"related":["idea-tr2-preclinical-negative-registry","idea-tr2-model-report-cards"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-reproducibility","b-negative-results"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Preclinical living reviews will reveal substantial publication bias (funnel asymmetry) for at least half of therapeutic hypotheses entering trials, and will change the decision to proceed or the trial design in at least a fifth of cases.","rationale":"Systematic review is the standard for clinical evidence; its absence for preclinical evidence means trials are launched on a biased sample of results.","test":"Produce living reviews for twenty hypotheses entering phase 1; report bias metrics and document whether the review changed any decision.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":2},{"id":"idea-moon-living-machine-readable-guidelines","kind":"idea","name":"Living, machine-readable guidelines pushed to the point of care in every country","aka":[],"tldr":"Cancer treatment guidance changes constantly and takes years to reach many clinics. Make guidelines live documents that software can read, updated as evidence arrives and adapted to what each country can afford.","summary":"Guidelines are published as prose, updated on annual cycles, and adapted slowly for resource-limited settings; diffusion of practice-changing evidence takes years. The proposal is a shared open format for computable guidelines (eligibility, options, evidence grades, resource tiers), a living update process triggered by trial results, and integration into electronic prescribing and decision support so that every treatment plan is checked against current, resource-appropriate guidance, with feedback on concordance by country and centre.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Knowledge reaches practice too slowly): Morris, Wooding & Grant, The answer is 17 years, what is the question (JRSM 2011)","url":"https://doi.org/10.1258/jrsm.2011.110180"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["asco","esmo"],"pathways":[],"terms":["standard-of-care"],"trials":[],"people":[],"bottlenecks":["b-knowledge-diffusion","b-global-access","b-care-fragmentation"],"keyPapers":["paper-morris-j-r-soc-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Computable living guidelines cut the median time from practice-changing trial to routine use from years to months and raise guideline concordance in participating low- and middle-income centres.","rationale":"Knowledge diffusion fails at the last mile; software can carry the update to every prescriber, and resource tiering (as NCCN Harmonized Guidelines began) makes the guidance applicable.","test":"Implement for three cancers across twenty centres in five countries; measure time to adoption of new evidence and concordance before and after.","maturity":"early-clinical","actor":"data","cost":"medium","horizonYears":3},{"id":"idea-acc-local-oral-morphine-production","kind":"idea","name":"Locally prepared oral morphine solution, licensed for nurse prescribing","aka":[],"tldr":"Uganda makes liquid morphine from powder in a simple facility and lets trained nurses prescribe it, giving pain relief to patients that no doctor will ever reach. Other countries could copy this within a year.","summary":"Hospice Africa Uganda pioneered reconstitution of oral morphine solution from imported powder at low cost, distributed through a public programme and prescribed by specially trained nurses and clinical officers under a 2004 regulation. The model has been documented and adapted in a handful of countries but not widely. A package combining pharmacy standards for reconstitution, a nurse-prescriber training curriculum, and model regulation would let ministries adopt it quickly.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Pain relief and palliative care are unavailable to most): WHO fact sheet, Palliative care","url":"https://www.who.int/news-room/fact-sheets/detail/palliative-care"}],"tags":[],"related":["idea-acc-balanced-opioid-policy-reform"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-palliative","b-global-access","b-workforce"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Countries adopting local oral morphine production with nurse prescribing will increase the number of patients receiving opioid analgesia at home by at least fivefold within three years at a drug cost under $0.05 per day.","rationale":"The Ugandan programme has run for more than two decades with no evidence of significant diversion; the constraints elsewhere are regulatory and logistical, both addressed by the package.","test":"Implementation in three countries with morphine dispensed, patients served, home pain scores, and diversion reports as endpoints.","maturity":"being-tested-at-scale","actor":"policy","cost":"small","horizonYears":2},{"id":"idea-tr2-cutpoint-lock","kind":"idea","name":"Lock the biomarker cut-off before phase 3, and publish it","aka":[],"tldr":"Companies sometimes choose the biomarker threshold that makes their trial look best after seeing the data. Requiring the threshold to be fixed and published before the big trial starts prevents this.","summary":"Cut-points for continuous biomarkers (PD-L1 percentages, HER2-low boundaries, ctDNA thresholds) are frequently selected from phase 2 data with multiple thresholds explored, and sometimes revised during phase 3. Regulators could require that the phase 3 protocol specify the cut-point and the assay version, derived from an independent training set, with the derivation report deposited in the trial registry before enrolment.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Biomarkers are not validated or standardised): Fernandez et al., Examination of low ERBB2 protein expression in breast cancer tissue (JAMA Oncology 2022)","url":"https://doi.org/10.1001/jamaoncol.2021.7239"}],"tags":[],"related":["idea-tr2-marker-stratified-default"],"cancers":[],"sections":[],"technologies":[],"targets":["pdl1"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["companion-diagnostic-term"],"trials":[],"people":[],"bottlenecks":["b-biomarker-validation","b-trial-design"],"keyPapers":["paper-fernandez-jama-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Trials with locked and published cut-points will show smaller shrinkage of the biomarker treatment interaction between phase 2 and phase 3 than trials with adaptive or post hoc cut-points.","rationale":"Optimism bias from cut-point selection is a known statistical phenomenon; pre-registration is the standard remedy for analytic flexibility.","test":"Audit the last 30 biomarker-restricted approvals for cut-point derivation and revision; implement the requirement and compare interaction estimates in subsequent trials.","maturity":"early-clinical","actor":"regulator","cost":"small","horizonYears":2},{"id":"idea-bio1-baseline-ultradeep-resistant-clones","kind":"idea","name":"Look for the resistant sub-population before the first dose","aka":[],"tldr":"Resistance mutations often exist in a tiny fraction of cells before treatment starts. Error-corrected sequencing that detects variants below 0.01 percent allele fraction could find them at diagnosis and prompt a mechanism-matched combination from day one.","summary":"Duplex or error-corrected sequencing detects variants below 0.01 percent allele fraction. Pre-existing resistance clones (EGFR T790M before first-generation TKIs, KRAS in colorectal cancer before anti-EGFR, ESR1 in breast cancer) predict early failure. The proposal is a baseline ultra-deep panel of known resistance alleles for every patient starting a targeted drug, with a pre-specified rule to add the mechanism-matched second agent if a clone is found.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Tumour heterogeneity and clonal evolution): Gerlinger et al., Intratumor heterogeneity and branched evolution (NEJM 2012)","url":"https://doi.org/10.1056/NEJMoa1113205"}],"tags":[],"related":[],"cancers":["nsclc","colorectal","breast-hr-positive"],"sections":[],"technologies":["liquid-biopsy","cgp"],"targets":["egfr","kras","estrogen-receptor"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["vaf"],"trials":[],"people":[],"bottlenecks":["b-tumor-heterogeneity","b-resistance"],"keyPapers":["paper-flaura-nejm-2018","paper-egfr-nsclc-lancet-oncol-2012","paper-egfr-nsclc-n-engl-j-med-2010"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Ultra-deep baseline detection of a resistance allele predicts progression within six months on monotherapy, and patients with detectable pre-existing clones who receive an upfront combination have progression-free survival matching those without such clones.","rationale":"Pre-existing resistance was shown for T790M and for KRAS in colorectal cancer; assays have improved by two orders of magnitude since those studies.","test":"Prospective observational study in 300 patients starting osimertinib or an anti-EGFR antibody: ultra-deep baseline plasma and tissue, blinded, correlated with time to progression; if predictive, a randomised combination trial in the clone-positive group.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":3},{"id":"idea-reg-losartan-pancreatic-stroma","kind":"idea","name":"Losartan to loosen the stroma of pancreatic cancer before chemotherapy: a phase 3","aka":[],"tldr":"A cheap blood pressure drug may soften the dense scar tissue around pancreatic tumours so chemotherapy and immune cells can get in. Early trials look encouraging.","summary":"Losartan inhibits angiotensin II and TGF-beta-driven fibrosis and, in mouse models, decompresses tumour vessels and improves drug delivery. A single-arm phase 2 (Massachusetts General Hospital) adding losartan to FOLFIRINOX and chemoradiation in locally advanced pancreatic cancer reported a high R0 resection rate, and a randomised phase 2 with added immunotherapy has followed. Losartan is off patent and costs a few dollars a month. The proposal is a publicly funded randomised phase 3 of losartan plus standard neoadjuvant therapy versus standard therapy alone in borderline resectable and locally advanced pancreatic cancer.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (No incentive to repurpose cheap drugs): Pantziarka et al., The Repurposing Drugs in Oncology (ReDO) Project (ecancer 2014)","url":"https://doi.org/10.3332/ecancer.2014.442"}],"tags":[],"related":[],"cancers":["pancreatic"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["mgh"],"pathways":["emt"],"terms":[],"trials":[],"people":[],"bottlenecks":["b-generic-repurposing","b-tme-immunosuppression"],"keyPapers":["paper-pantziarka-ecancermedicalscience"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Adding losartan to neoadjuvant chemotherapy increases the R0 resection rate by at least 15 absolute percentage points and improves overall survival in locally advanced pancreatic cancer.","rationale":"Stromal desmoplasia is the defining obstacle in pancreatic cancer and many expensive stroma-targeting agents have failed; losartan's mechanism is supported by imaging and tissue data in patients, and its safety is well known.","test":"Randomised phase 3 of roughly 400 patients with R0 resection rate and OS endpoints, with imaging biomarkers of tumour perfusion in a sub-study.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":5},{"id":"idea-acc-frugal-hdr-brachytherapy","kind":"idea","name":"Low-cost cobalt-60 brachytherapy for cervical cancer in every regional centre","aka":[],"tldr":"Cervical cancer cannot be cured by external radiotherapy alone; it needs brachytherapy, internal radiation that LMIC radiotherapy centres frequently lack or cannot keep running because iridium-192 sources must be replaced every three months. Cobalt-60 sources last about five years and give equivalent doses, so funding cobalt units for every regional centre closes a well-understood cure gap.","summary":"Brachytherapy is essential for curative cervical cancer treatment, yet LMIC radiotherapy centres frequently have none, or have units whose iridium-192 sources cannot be replaced every three months for cost and logistics reasons. Cobalt-60 HDR sources last about five years and are dosimetrically equivalent for cervix. A programme to fund cobalt HDR units, standardise applicators and image-guided planning, and train teams would close a specific and well-understood cure gap.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Most of the world has almost no cancer care): WHO fact sheet, Cancer","url":"https://www.who.int/news-room/fact-sheets/detail/cancer"}],"tags":[],"related":[],"cancers":["cervical"],"sections":["radiation"],"technologies":["brachytherapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-global-access","b-surgery-radiation-innovation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Regional centres receiving a cobalt HDR unit and training will increase the proportion of locally advanced cervical cancer patients completing brachytherapy within the recommended overall treatment time from under 40% to above 80%.","rationale":"The technology is proven and the indication is common; the constraint is a solvable procurement and training problem with a defined cost.","test":"Before-and-after audit of brachytherapy completion, overall treatment time, and three-year local control in ten centres receiving units.","maturity":"early-clinical","actor":"engineering","cost":"medium","horizonYears":3},{"id":"idea-moon-olanzapine-antiemetic-everywhere","kind":"idea","name":"Low-dose olanzapine and generic antiemetic bundles in every guideline and formulary","aka":[],"tldr":"A cheap, old antipsychotic at a low dose is one of the best anti-sickness drugs for chemotherapy. Make sure every cancer unit in the world uses it.","summary":"Olanzapine 5 to 10 mg reduces chemotherapy-induced nausea and vomiting in randomised trials, including with highly emetogenic regimens, at a cost of pennies. Uptake is uneven, and in many low-income settings even standard 5-HT3 antagonists and dexamethasone are inconsistently available. The proposal is a global implementation programme: inclusion of olanzapine-based bundles in national essential medicines lists and guidelines, pre-printed order sets, and audit of complete response rates as a quality indicator.","asOf":"2026-09-08","links":[{"label":"WHO Model List of Essential Medicines","url":"https://list.essentialmeds.org/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol","b-global-access","b-generic-repurposing"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Implementation raises complete control of nausea and vomiting in highly emetogenic chemotherapy above 70% in participating units and reduces emergency visits for vomiting and dehydration.","rationale":"The evidence is done; the gap is diffusion. Nausea is among the most feared toxicities and among the cheapest to control.","test":"Before-and-after audit with a randomised implementation-support arm across cancer units in three middle-income countries; primary endpoint complete response rate in cycle 1.","maturity":"being-tested-at-scale","actor":"clinic","cost":"small","horizonYears":2},{"id":"idea-prev-low-dose-tamoxifen-uptake","kind":"idea","name":"Low-dose tamoxifen for high-risk women, prescribed by pharmacists and nurses","aka":[],"tldr":"A 5 mg tamoxifen dose halves breast cancer recurrence after precancer with far fewer side effects than the full dose. Almost nobody is prescribed it. Change who can prescribe.","summary":"TAM-01 showed 5 mg a day reduced recurrence after DCIS, atypical hyperplasia or LCIS by about half with side effects close to placebo, yet uptake of risk-reducing medication is under 10%. Propose nurse and pharmacist prescribing, an automatic offer at diagnosis of high-risk lesions, and inclusion in screening-risk feedback.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Prevention we already have is not deployed): Islami et al., Proportion of cancer attributable to modifiable risk factors (CA 2018)","url":"https://doi.org/10.3322/caac.21440"}],"tags":[],"related":[],"cancers":["breast-hr-positive"],"sections":["prevention","hormonal"],"technologies":["chemoprevention","endocrine-therapy"],"targets":["estrogen-receptor"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption"],"keyPapers":["paper-islami-ca-cancer-j-clin"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Automatic offer plus non-physician prescribing raises uptake of risk-reducing medication among eligible women from under 10% to at least 40%.","rationale":"The barriers are prescriber inertia and fear of side effects; low dose addresses the second, delegation the first.","test":"Run a cluster RCT in breast units.","maturity":"early-clinical","actor":"clinic","cost":"small","horizonYears":3},{"id":"idea-prev-lung-screening-risk-model-eligibility","kind":"idea","name":"Lung screening eligibility by risk score, not pack-years, including high-risk never-smokers","aka":[],"tldr":"Pack-year rules miss people who get lung cancer without heavy smoking, including East Asian women who never smoked, as Taiwan's TALENT study showed. Eligibility by a validated risk model with a set threshold, plus a never-smoker arm where family history matters, would find more cancers per scan.","summary":"PLCOm2012 risk-based selection is more efficient than USPSTF criteria; Taiwan's TALENT study found high detection in never-smoking women with family history. Propose eligibility by a validated risk model with a threshold (e.g. 1.5% six-year risk) plus a never-smoker arm for populations with high never-smoker incidence.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The hardest cancers are found late): Crosby et al., Early detection of cancer (Science 2022)","url":"https://doi.org/10.1126/science.aay9040"}],"tags":[],"related":["lung-cancer-evidence-roadmap","idea-lung-screening-eligibility-by-risk-not-pack-years"],"cancers":["nsclc"],"sections":["early-detection"],"technologies":["ct"],"targets":["egfr"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-early-detection","b-trial-diversity"],"keyPapers":["paper-crosby-science"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Risk-model eligibility increases cancers detected per 1,000 scans by at least 30%, and never-smoker criteria in East Asian populations achieve detection rates comparable to smoker screening.","rationale":"Screening efficiency scales with baseline risk; never-smoker EGFR-mutant lung cancer in East Asian women is a distinct epidemic not captured by tobacco criteria.","test":"Pragmatic comparison within a national programme (England's Targeted Lung Health Check) and a never-smoker RCT in Taiwan, China, or Korea with mortality follow-up.","maturity":"being-tested-at-scale","actor":"policy","cost":"medium","horizonYears":5},{"id":"idea-bio1-macrocycle-ppi-campaign","kind":"idea","name":"Macrocyclic peptides to cover protein surfaces that pills cannot","aka":[],"tldr":"Undruggable cancer proteins such as beta-catenin, MYC and KRAS act through broad flat protein-protein interfaces that small pills cannot cover. Ring-shaped macrocyclic peptides can, some series are cell-permeable, and mRNA display can screen trillions of candidates; the proposal is a focused campaign with open publication of permeability rules.","summary":"Protein-protein interfaces are the defining feature of undruggable targets. Macrocycles occupy a chemical space between small molecules and biologics, with demonstrated cell permeability in some series, and mRNA display can screen trillions of candidates in a single tube. A focused campaign against a defined list of oncology interfaces (for example beta-catenin/TCF, MYC/MAX, KRAS/SOS) with open publication of permeability rules would advance both the targets and the modality.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The undruggable drivers): Dang et al., Drugging the 'undruggable' cancer targets (Nature Reviews Cancer 2017)","url":"https://doi.org/10.1038/nrc.2017.36"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["circle-pharma","generate-biomedicines"],"institutions":[],"pathways":["wnt","ras-mapk"],"terms":[],"trials":[],"people":[],"bottlenecks":["b-undruggable-targets"],"keyPapers":["paper-dang-nat-rev-cancer"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"mRNA display campaigns against three oncology protein interfaces produce cell-permeable macrocycles with sub-100 nM cellular activity in at least one case.","rationale":"Macrocycles have already produced clinical candidates for previously intractable targets outside oncology; the field's bottleneck is permeability design rules, which are learnable from systematic data.","test":"Run parallel display selections, measure cellular target engagement by NanoBRET, and publish a permeability dataset that others can model.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":6},{"id":"idea-acc-registries-as-aid-condition","kind":"idea","name":"Make a population cancer registry a condition of every cancer aid programme","aka":[],"tldr":"You cannot fix what you cannot count. Every donor-funded cancer programme should fund and require a population-based cancer registry so results can be measured over time.","summary":"Fewer than one in five people in Africa are covered by a high-quality population-based cancer registry, so GLOBOCAN estimates for the uncovered countries are extrapolations. Registries are cheap relative to treatment programmes and are the only way to see stage shift, survival, and coverage. The proposal is a coordinated donor policy: a fixed percentage of every cancer grant supports a registry meeting IARC Global Initiative for Cancer Registry Development standards, with data deposited in the Global Cancer Observatory.","asOf":"2026-09-08","links":[{"label":"Global Cancer Observatory (IARC)","url":"https://gco.iarc.fr/"}],"tags":[],"related":["globocan","seer"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["iarc"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-global-access","b-real-world-evidence","b-data-silos"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Countries where registry funding is bundled with cancer programmes will reach high-quality registry coverage of at least 30% of their population within five years, against under 10% for comparators.","rationale":"IARC's GICR hubs have shown that modest, sustained support produces usable registries; the missing piece is consistent funding rather than method.","test":"Track registry coverage, data quality indicators, and inclusion in Cancer Incidence in Five Continents for countries under the policy versus those outside it.","maturity":"speculative","actor":"philanthropy","cost":"medium","horizonYears":4},{"id":"idea-prev-dental-oral-exam-standard","kind":"idea","name":"Make a two-minute mouth cancer check part of every dental visit","aka":[],"tldr":"Dentists see the mouth more than any doctor. A standard, recorded oral cancer examination with a referral route would catch cancers earlier at almost no cost.","summary":"Dentists see the mouth more than any doctor, so this idea mandates a coded, recorded two-minute oral mucosal examination at every dental check for adults aged 40 and over, with photo documentation and a referral pathway. Oral and oropharyngeal cancers are rising with HPV and often present late despite being visible; dentists already examine inconsistently, and coding plus a pathway create accountability and data. The aim is to shift oral cancer diagnosis towards stage I-II at almost no cost. The test is a regional stepped-wedge rollout with registry linkage. Speculative in maturity, it addresses the bottlenecks The hardest cancers are found late and Prevention we already have is not deployed.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The hardest cancers are found late): Crosby et al., Early detection of cancer (Science 2022)","url":"https://doi.org/10.1126/science.aay9040"}],"tags":[],"related":[],"cancers":["head-and-neck"],"sections":["early-detection"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-early-detection","b-prevention-adoption"],"keyPapers":["paper-crosby-science"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Mandated recorded oral examinations increase stage I-II oral cancer diagnosis by at least 10 percentage points within five years.","rationale":"Dentists already do it inconsistently; coding and a pathway create accountability and data.","test":"Run a regional stepped-wedge rollout with registry linkage.","maturity":"speculative","actor":"policy","cost":"small","horizonYears":4},{"id":"idea-bio1-somatic-crispr-gemms","kind":"idea","name":"Make bespoke mouse cancer models in weeks with in vivo gene editing","aka":[],"tldr":"Building a genetically engineered mouse for a specific cancer takes years. Editing genes directly in an adult mouse's organ can produce the same tumour in weeks.","summary":"Somatic genome editing by electroporation, viral delivery or lipid nanoparticles into a target organ produces autochthonous tumours with intact immune systems and native microenvironment, at a fraction of the time and cost of germline models. This has been demonstrated in lung, pancreas, liver and brain. Combinatorial guide libraries also allow genotype-response mapping in immunocompetent animals.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Lab models that fail to predict what happens in patients): Wong, Siah & Lo, Estimation of clinical trial success rates (Biostatistics 2019)","url":"https://doi.org/10.1093/biostatistics/kxx069"}],"tags":[],"related":[],"cancers":["nsclc","pancreatic","glioblastoma"],"sections":[],"technologies":["crispr-screens","pdx-models"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-preclinical-models"],"keyPapers":["paper-wong-biostatistics"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Somatic-editing models reproduce the histology, immune contexture and therapy response of matched germline models while reducing time to model from years to under three months.","rationale":"Immunocompetent, genotype-defined models are the scarcest resource in translational oncology; the editing tools now exist and the bottleneck is standardisation and sharing of protocols.","test":"Direct comparison of somatic and germline models for three well-characterised genotypes on histology, immune profiling and response to a standard agent.","maturity":"preclinical-evidence","actor":"research","cost":"small","horizonYears":3},{"id":"idea-prev-very-low-nicotine-mandate","kind":"idea","name":"Make cigarettes non-addictive by capping their nicotine","aka":[],"tldr":"Cigarettes with nicotine cut by 95% do not sustain addiction. A mandatory cap, which the FDA has proposed, could cut smoking dramatically.","summary":"Randomised trials show cigarettes with nicotine cut by 95% reduce consumption and increase quitting. The FDA issued a proposed product standard in January 2025. Propose finalisation and adoption by other regulators, with pre-planned surveillance of compensatory smoking, illicit trade, and switching to alternatives.","asOf":"2026-09-08","links":[{"label":"FDA tobacco products","url":"https://www.fda.gov/tobacco-products"}],"tags":[],"related":[],"cancers":["nsclc"],"sections":["prevention"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A nicotine cap reduces adult smoking prevalence by at least 30% within five years of implementation.","rationale":"Addiction requires nicotine; supply-side product standards avoid relying on individual behaviour change.","test":"Adoption in one jurisdiction with synthetic-control evaluation of prevalence and sales.","maturity":"being-tested-at-scale","actor":"regulator","cost":"small","horizonYears":5},{"id":"idea-bio1-clonal-clearance-endpoint","kind":"idea","name":"Make clonal clearance, not tumour shrinkage, a trial endpoint","aka":[],"tldr":"A drug that shrinks a tumour by half but leaves the resistant sub-population untouched will fail. Trials should measure whether every sub-population is cleared, not just overall size.","summary":"Response criteria (RECIST) measure bulk diameter; ctDNA endpoints measure total variant allele fraction. Neither captures whether all subclones are suppressed. A clonal clearance endpoint, defined as undetectable plasma signal for every baseline-identified subclone at a fixed timepoint, could be validated as a surrogate and used in early-phase trials to distinguish drugs that shrink from drugs that eradicate.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Tumour heterogeneity and clonal evolution): Gerlinger et al., Intratumor heterogeneity and branched evolution (NEJM 2012)","url":"https://doi.org/10.1056/NEJMoa1113205"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["liquid-biopsy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["recist","ctdna","pfs"],"trials":[],"people":[],"bottlenecks":["b-tumor-heterogeneity","b-trial-design"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Clonal clearance at 12 weeks predicts progression-free survival better than RECIST response or bulk ctDNA clearance, and drugs that achieve it more often produce longer durations of response in later trials.","rationale":"Bulk response is dominated by the largest clone; durable benefit depends on the smallest resistant clone. The measurement is now feasible with multi-region baseline tissue and deep plasma sequencing.","test":"Retrospective validation on serial plasma from two completed targeted-therapy trials with baseline multi-region tissue; if predictive, propose to regulators as an exploratory endpoint for phase 2.","maturity":"speculative","actor":"regulator","cost":"medium","horizonYears":4},{"id":"idea-cost-early-palliative-default","kind":"idea","name":"Make early palliative care and a goals conversation part of every advanced-cancer pathway","aka":[],"tldr":"Chemotherapy in the last two weeks of life rarely helps and costs a great deal; patients who have an early conversation about what matters to them choose it less often and live at least as long.","summary":"Randomised trials of early specialist palliative care alongside cancer treatment in advanced lung and other cancers have shown better quality of life, less aggressive end-of-life care and, in some trials, longer survival. ASCO's Choosing Wisely list names chemotherapy for patients with poor performance status and no benefit from prior treatment as care to avoid. Embedding a structured serious-illness conversation at the start of any non-curative line, and automatic palliative referral at metastatic diagnosis, changes the default without restricting anyone's choice.","asOf":"2026-09-10","links":[{"label":"ASCO: Choosing Wisely recommendations","url":"https://www.asco.org/news-initiatives/current-initiatives/cancer-care-initiatives/choosing-wisely"}],"tags":[],"related":[],"cancers":[],"sections":["supportive-care"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["asco","mascc"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-palliative","b-toxicity-qol","b-incentive-misalignment"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Default early palliative referral will reduce chemotherapy in the last 14 days of life and intensive-care admissions in the last 30 days by a third, with no reduction in survival and lower end-of-life spending.","rationale":"The trials are done; uptake is limited by workforce and by the absence of a pathway trigger.","test":"Health-system pathway change with end-of-life quality indicators, patient-reported outcomes and spending compared with matched systems.","maturity":"being-tested-at-scale","actor":"clinic","cost":"small","horizonYears":2},{"id":"idea-moon-cold-to-hot-programme","kind":"idea","name":"Make every cold tumour hot: a coordinated programme to reprogramme immune-excluded tumours","aka":[],"tldr":"Immunotherapy works in tumours that immune cells can enter and ignores those that shut them out. Systematically test ways to open up the shut-out tumours, measured with spatial maps.","summary":"Most pancreatic, prostate, colorectal (microsatellite-stable), ovarian and glioma tumours are immune-excluded or immune-desert. Candidate strategies include stromal modulation (FAP, TGF-beta, CXCR4 antagonists), innate agonists (STING, TLR), oncolytic viruses, radiotherapy priming, and myeloid reprogramming (CD47, CSF1R). Each has been tested piecemeal. The proposal is a coordinated programme with standardised spatial immune profiling before and after each intervention in window-of-opportunity trials, a shared classification of exclusion mechanisms, and adaptive combination trials that match the mechanism of exclusion to the reprogramming strategy.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Cold tumours and the immunosuppressive microenvironment): Haslam & Prasad, Estimation of the percentage of US patients eligible for and responding to checkpoint inhibitors (JAMA Netw Open 2019)","url":"https://doi.org/10.1001/jamanetworkopen.2019.2535"}],"tags":[],"related":[],"cancers":["pancreatic","colorectal","prostate","ovarian"],"sections":[],"technologies":["single-cell-spatial","sting-agonist","oncolytic-virus","checkpoint-inhibitor"],"targets":["fap","cd47"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["cold-vs-hot"],"trials":[],"people":[],"bottlenecks":["b-tme-immunosuppression","b-immunotherapy-response"],"keyPapers":["paper-haslam-jama-netw-open","paper-cd47-pancreatic-pharmacol-res-2022","paper-cd47-colorectal-cancers-basel-2025","paper-cd47-colorectal-cancer-res-commun-2025"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Mechanism-matched reprogramming converts at least a third of treated cold tumours to inflamed phenotypes on spatial profiling and produces objective responses to checkpoint inhibition in indications where they are currently rare.","rationale":"Exclusion has multiple distinct mechanisms; unselected combinations have failed because the mechanism was not matched. Spatial profiling now makes matching feasible.","test":"Window-of-opportunity platform in pancreatic and microsatellite-stable colorectal cancer with paired biopsies; primary endpoint conversion rate on spatial immune score, secondary response to subsequent checkpoint inhibitor.","maturity":"preclinical-evidence","actor":"research","cost":"large","horizonYears":8},{"id":"idea-bio2-metastasis-screen-standard","kind":"idea","name":"Make in vivo metastasis screens a required step in drug discovery","aka":[],"tldr":"Drug candidates are tested for shrinking tumours, almost never for stopping spread. A standard spread test would find anti-metastatic drugs we are throwing away.","summary":"Barcoded in vivo CRISPR and lineage-tracing screens can quantify seeding, survival in circulation and outgrowth as separate phenotypes. Very few programmes run them, so anti-metastatic activity is invisible during discovery. Funders could require a standard metastasis panel (spontaneous metastasis from orthotopic implantation plus a barcoded seeding assay) from any grant or programme claiming anti-metastatic intent.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Metastasis is understood least and studied last): Dillekås et al., Are 90% of deaths from cancer caused by metastases? (Cancer Medicine 2019)","url":"https://doi.org/10.1002/cam4.2474"}],"tags":[],"related":["depmap","cancer-models"],"cancers":[],"sections":[],"technologies":["crispr-screens","pdx-models","organoids"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-metastasis-biology","b-preclinical-models","b-negative-results"],"keyPapers":["paper-dillekas-cancer-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Compounds active in standardised seeding and outgrowth assays but inactive in subcutaneous growth assays exist at a rate of at least 5% in current oncology libraries, and are being discarded today.","rationale":"Metastasis is a distinct set of phenotypes with distinct genetic dependencies, so screening only for proliferation systematically selects against anti-metastatic mechanisms. Barcoded clonal tracking gives quantitative, well-powered readouts from few animals.","test":"Rescreen 2,000 shelved oncology compounds from academic and industry libraries in a barcoded orthotopic seeding assay for two tumour types, and publish all hits and misses openly.","maturity":"preclinical-evidence","actor":"research","cost":"small","horizonYears":4},{"id":"idea-acc-hypofractionation-default-lmic","kind":"idea","name":"Make one-week radiotherapy the default in overloaded systems","aka":[],"tldr":"Giving radiotherapy in five larger doses over one week instead of 15 to 25 smaller doses is non-inferior for cancer control and late toxicity in breast and prostate cancer, and triples the number of patients each machine can treat. The barriers are guideline inertia and payment per fraction, not hardware.","summary":"Randomised trials (FAST-Forward in breast, several in prostate) show that ultra-hypofractionated schedules are non-inferior for cancer control and late toxicity. In systems where the queue for a machine is the limiting factor, adopting these schedules as the national default protocol is the fastest capacity gain available, without any new hardware. The barrier is guideline inertia and fee-for-fraction payment.","asOf":"2026-09-08","links":[{"label":"FAST-Forward trial (Lancet 2020)","url":"https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30932-6/fulltext"}],"tags":[],"related":[],"cancers":["breast-hr-positive","prostate"],"sections":["radiation"],"technologies":["imrt-igrt","sbrt"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-global-access","b-surgery-radiation-innovation","b-knowledge-diffusion"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"National adoption of five-fraction breast and prostate protocols in a country with fewer than one machine per million people will increase the number of patients starting radiotherapy within 30 days of referral by at least 50% within 18 months.","rationale":"Machine throughput scales inversely with fraction number; the evidence base is Level 1 and the schedules are simpler for patients who travel long distances. Fee-for-fraction reimbursement is the main disincentive and can be changed by decree.","test":"A stepped-wedge national rollout with per-centre audit of fraction numbers, waiting times, and two-year local-control and toxicity outcomes against the pre-rollout cohort.","maturity":"being-tested-at-scale","actor":"clinic","cost":"small","horizonYears":2},{"id":"idea-tr2-paediatric-combo-prea","kind":"idea","name":"Make paediatric combination studies part of every relevant adult cancer drug approval","aka":[],"tldr":"Children's cancers are treated with combinations, but companies study new drugs in children one at a time. Approvals should require the combination study children actually need.","summary":"The US RACE for Children Act requires paediatric evaluation of molecularly targeted adult cancer drugs, but permits single-agent studies that rarely lead to use, because paediatric standards of care are multi-drug backbones. Requiring the paediatric plan to include a combination with the relevant backbone, designed with cooperative groups, would produce actionable evidence.","asOf":"2026-09-08","links":[{"label":"FDA paediatric oncology","url":"https://www.fda.gov/about-fda/oncology-center-excellence/pediatric-oncology"}],"tags":[],"related":["childrens-oncology-group"],"cancers":["neuroblastoma","all-leukemia"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-combination-space","b-rare-cancers"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Drugs whose paediatric plans include a backbone combination will reach paediatric labelling or guideline inclusion at least twice as often within seven years as drugs studied as single agents.","rationale":"Nearly every paediatric oncology advance came from adding an agent to an existing backbone in a cooperative-group trial, not from monotherapy.","test":"Compare paediatric labelling outcomes for agents studied in combination versus monotherapy under current paediatric plans, then pilot the requirement with two new agents.","maturity":"speculative","actor":"regulator","cost":"medium","horizonYears":5},{"id":"idea-bio1-approval-linked-progression-sampling","kind":"idea","name":"Make post-progression sampling a condition of accelerated approval","aka":[],"tldr":"Drugs approved on early evidence come with follow-up obligations. One of them should be finding out how tumours escape the new drug.","summary":"Accelerated approvals already carry confirmatory trial requirements. Adding a resistance-characterisation commitment (a specified number of paired progression samples with mechanism reporting into a public database within a defined period) would ensure the field learns how each new agent fails while the drug is still early in its lifecycle, rather than a decade later.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Acquired resistance to every therapy): Soria et al., Osimertinib in untreated EGFR-mutated NSCLC (FLAURA, NEJM 2018)","url":"https://doi.org/10.1056/NEJMoa1713137"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["accelerated-approval","resistance"],"trials":[],"people":[],"bottlenecks":["b-resistance","b-regulatory-fragmentation","b-negative-results"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Approval-linked sampling commitments produce mechanism data for new agents years earlier than the status quo and demonstrably shape the design of successor agents and combinations.","rationale":"Post-marketing requirements are an established regulatory instrument and are already used for dose optimisation under Project Optimus; the incremental cost to a sponsor is small relative to the value of the information.","test":"Apply the requirement to a small number of new approvals as a pilot and compare time-to-first-published-mechanism with matched historical approvals.","maturity":"speculative","actor":"regulator","cost":"small","horizonYears":5},{"id":"idea-reg-global-dose-optimisation-guideline","kind":"idea","name":"Make pre-approval dose optimisation an ICH standard so it is done once worldwide","aka":[],"tldr":"The FDA now asks companies to find the right dose of a cancer drug before approval. If every regulator asked the same way, companies would do it once and doses would match worldwide.","summary":"FDA's Project Optimus (guidance finalised 2024) expects randomised dose comparison before approval for oncology drugs; other regulators have not formally adopted it, so sponsors face different expectations and may launch different doses in different regions. The proposal is an ICH efficacy guideline codifying dose-optimisation expectations for oncology (randomised comparison of at least two doses, exposure-response, tolerability endpoints) so that one programme serves all regions and approved doses converge.","asOf":"2026-09-08","links":[{"label":"FDA Project Optimus","url":"https://www.fda.gov/about-fda/oncology-center-excellence/project-optimus"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":["sotorasib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-regulatory-fragmentation","b-dose-optimisation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"After adoption, the proportion of new oncology approvals with different approved doses in different regions falls to near zero, and the rate of post-approval dose reductions in labels falls by half.","rationale":"Historical maximum-tolerated-dose development left many targeted drugs approved at doses later shown to be excessive (sotorasib and several kinase inhibitors). Divergent regional expectations multiply cost and delay adoption of the better dose.","test":"ICH concept paper and expert working group; track regional dose divergence and label dose changes for products developed under the guideline against the prior five-year cohort.","maturity":"early-clinical","actor":"regulator","cost":"small","horizonYears":4},{"id":"idea-lung-resistance-directed-sequencing-at-every-progression","kind":"idea","name":"Make resistance a diagnosis: sequence at every progression and choose the next line from what the tumour became","aka":[],"tldr":"When a targeted drug stops working, the tumour has usually changed in a way you can read. Most patients still move to the next treatment on a protocol rather than on a test of what actually happened.","summary":"Sequist's 37 re-biopsied patients showed that acquired resistance to EGFR inhibitors is a heterogeneous set of diagnoses: T790M, MET amplification, PIK3CA mutation, a change of cell state, and in 14 percent an outright transformation into small-cell lung cancer, which is sensitive to entirely different drugs. Three patients lost their resistance mechanism when the drug was withdrawn and responded again. Kobayashi's single patient in 2005 produced osimertinib.\n\nDespite this, sequencing at progression is inconsistent: tissue re-biopsy is invasive and often declined, plasma testing is not reimbursed everywhere, and the result frequently arrives after the next line has started. The idea is to make a resistance profile, tissue where safe and plasma always, a required step before the next line, and to fund the pathway that makes it fast enough to act on.","asOf":"2026-09-25","links":[],"tags":["lung-evidence"],"related":["ctdna-tests","diagnostics-roadmap","lung-cancer-evidence-roadmap"],"cancers":["lung-cancer","nsclc","egfr-mutant-nsclc","alk-positive-nsclc"],"sections":["targeted-therapy","diagnostics"],"technologies":["ngs","liquid-biopsy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["resistance","ctdna"],"trials":[],"people":[],"bottlenecks":["b-resistance","b-tumor-heterogeneity","b-care-fragmentation","b-data-silos"],"keyPapers":["paper-sequist-genotypic-histological-evolution-egfr-resistance-sci-transl-med-2011","paper-kobayashi-egfr-t790m-gefitinib-resistance-nejm-2005","paper-mariposa-nejm-2024","paper-tracerx-100-nejm-2017"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Mandatory molecular profiling at progression on targeted therapy, with a turnaround short enough to choose the next line, improves survival after first progression compared with protocol-driven sequencing, chiefly by finding the histological transformations and the actionable bypass alterations that are currently missed.","rationale":"The mechanisms are known, the assays exist, and at least one of them (small-cell transformation) changes treatment completely and is invisible without a biopsy. Amivantamab's activity against MET-driven bypass resistance, and the existence of drugs for MET, HER2 and RET alterations arising on treatment, mean a profile increasingly has somewhere to go. The reversibility finding also suggests a drug holiday is a testable strategy rather than a curiosity.","test":"A randomised strategy trial at first progression on a targeted therapy: profiling-directed next line (tissue plus plasma, result within 14 days) against physician's choice, with overall survival from progression as the primary endpoint and the rate of histological transformation detected as a key secondary. Plausible inside existing molecular tumour board networks; three to four years.","maturity":"early-clinical","actor":"clinic","cost":"medium","horizonYears":5},{"id":"idea-cost-extended-interval-default","kind":"idea","name":"Make six-weekly immunotherapy the default schedule","aka":[],"tldr":"Pembrolizumab 400 mg every six weeks is approved and works like 200 mg every three weeks, and it halves the number of clinic visits, infusion chairs and travel days without changing the drug bill.","summary":"The FDA approved pembrolizumab 400 mg every six weeks in 2020 on pharmacokinetic modelling and later clinical data; nivolumab 480 mg every four weeks has a similar basis. The drug quantity is the same, so the saving is in administration fees, chair time, staff, and patients' travel and time off work. Many practices still default to three-weekly schedules. A default schedule change in electronic order sets, with the shorter interval reserved for patients who need frequent review, is the cheapest capacity gain available in immunotherapy.","asOf":"2026-09-10","links":[{"label":"FDA: pembrolizumab label (Drugs@FDA)","url":"https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=125514"}],"tags":[],"related":[],"cancers":[],"sections":["immunotherapy"],"technologies":["checkpoint-inhibitor"],"targets":[],"drugs":["pembrolizumab","nivolumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-dose-optimisation","b-care-fragmentation","b-workforce"],"keyPapers":["paper-checkmate-017-nejm-2015","paper-keynote-189-nejm-2018","paper-keynote-564-nejm-2021"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Default extended-interval ordering will halve infusion visits for eligible patients within six months, reduce administration and travel cost per patient by at least 40%, and show no difference in survival or immune-related toxicity.","rationale":"The regulator has already accepted equivalence; the barrier is order-set inertia and fee-for-visit payment.","test":"Health-system order-set change with a difference-in-differences comparison against systems that did not switch, on visits, costs, adverse events and survival.","maturity":"being-tested-at-scale","actor":"clinic","cost":"small","horizonYears":1},{"id":"idea-prev-omit-radiotherapy-low-risk-breast-default","kind":"idea","name":"Make skipping radiotherapy the default for very low-risk breast cancer","aka":[],"tldr":"Trials show older women with the lowest-risk breast cancers gain almost nothing from radiotherapy after lumpectomy. Yet most still get it. Track and reward omission.","summary":"LUMINA, PRIME II and IDEA show low local recurrence without radiotherapy in luminal A breast tumours in older women, yet most still receive it, so this idea makes omission the default pathway, with PAM50 genomic confirmation where needed, and tracks it as a quality metric. The evidence exists; the barrier is inertia and fee-for-service incentives, so payers would measure omission rate and five-year local recurrence. The test is a stepped-wedge implementation across cancer centres with registry follow-up. Being tested at scale, it addresses the bottlenecks Overdiagnosis and false alarms, Toxicity and quality of life are undervalued and Incentives reward me-too drugs and marginal gains.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Overdiagnosis and false alarms): Welch & Black, Overdiagnosis in cancer (JNCI 2010)","url":"https://doi.org/10.1093/jnci/djq099"}],"tags":[],"related":[],"cancers":["breast-hr-positive"],"sections":["radiation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["pam50"],"trials":[],"people":[],"bottlenecks":["b-overdiagnosis","b-toxicity-qol","b-incentive-misalignment"],"keyPapers":["paper-welch-j-natl-cancer-inst"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A default-omission pathway raises radiotherapy omission from about 20% to at least 60% of eligible patients with five-year local recurrence of 3% or less.","rationale":"The evidence exists; the barrier is inertia and fee-for-service incentives.","test":"Stepped-wedge implementation across cancer centres with registry follow-up.","maturity":"being-tested-at-scale","actor":"payer","cost":"small","horizonYears":4},{"id":"idea-acc-broad-eligibility-as-regulatory-default","kind":"idea","name":"Make sponsors justify every trial exclusion of older and multimorbid patients","aka":[],"tldr":"Most cancer patients are over 65 and a large share have other illnesses, yet trials routinely exclude them on organ function, prior cancers, HIV or brain metastases. Regulators should require sponsors to justify each exclusion, include patients with controlled comorbidities by default, drop upper age limits, and report enrolment over 75 in labels.","summary":"ASCO and Friends of Cancer Research published recommendations to broaden eligibility (organ function thresholds, prior malignancies, HIV, brain metastases) and the FDA issued guidance, but uptake in industry protocols is partial. A regulatory requirement that each eligibility exclusion be justified in the protocol, with default inclusion of patients with controlled comorbidities and no upper age limit, would shift the baseline. Enrolment of patients over 75 should be reported in labels.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Older and multimorbid patients are excluded and undertreated): Mohile et al., Evaluation of geriatric assessment and management on toxic effects of cancer treatment (GAP70+, Lancet 2021)","url":"https://doi.org/10.1016/S0140-6736(21)01789-X"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["accelerated-approval"],"trials":[],"people":[],"bottlenecks":["b-aging-comorbidity","b-trial-diversity","b-trial-design"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Protocols under a justification requirement will enrol at least twice the proportion of patients over 75 and with significant comorbidity, with no material change in trial timelines.","rationale":"Exclusions are copied between protocols by habit rather than evidence; making them costly to include changes the default.","test":"Compare age and comorbidity distributions in registration trials submitted before and after the requirement, and correlate with post-marketing safety signals.","maturity":"early-clinical","actor":"regulator","cost":"small","horizonYears":3},{"id":"idea-cost-biosimilar-default-substitution","kind":"idea","name":"Make the biosimilar the default at the pharmacy for trastuzumab, bevacizumab and rituximab","aka":[],"tldr":"Copies of the big antibody drugs are approved and cheaper, but uptake depends on each prescriber; letting the pharmacy substitute the biosimilar unless the oncologist objects would move most patients within a year.","summary":"FDA-approved biosimilars of trastuzumab, bevacizumab, rituximab and pegfilgrastim have been on the US market since 2019. IQVIA estimated that biosimilars saved $56 billion over the decade to 2022 and projected $181 billion more over 2023 to 2027. Uptake still varies widely by practice because substitution requires a prescriber decision, a payer preference and a purchasing contract to line up. A default-substitution rule (opt-out rather than opt-in), combined with the flat-fee payment idea, removes the friction. NHS England and several European systems achieved over 90% uptake this way.","asOf":"2026-09-10","links":[{"label":"IQVIA Institute: Biosimilars in the United States 2023-2027 (January 2023)","url":"https://www.iqvia.com/insights/the-iqvia-institute/reports-and-publications/reports/biosimilars-in-the-united-states-2023-2027"},{"label":"FDA: Biosimilars","url":"https://www.fda.gov/drugs/therapeutic-biologics-applications-bla/biosimilars"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":["trastuzumab","trastuzumab-biosimilars","bevacizumab","rituximab"],"companies":[],"institutions":[],"pathways":[],"terms":["biosimilar"],"trials":[],"people":[],"bottlenecks":["b-drug-pricing","b-knowledge-diffusion"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Default substitution in a payer's network will lift biosimilar share for the three antibodies above 85% within twelve months, from a baseline that varies between 40% and 80%.","rationale":"Biosimilars have no clinically meaningful difference by regulatory definition; the remaining barrier is process, not evidence.","test":"A payer-level stepped rollout across regions with biosimilar share, drug spend and any switch-related adverse events reported quarterly.","maturity":"being-tested-at-scale","actor":"payer","cost":"small","horizonYears":2},{"id":"idea-rejuv-exposure-record-a-machine-can-read","kind":"idea","name":"Make the treatment exposure record machine-readable, so surveillance can be computed","aka":[],"tldr":"Risk-based follow-up guidelines key surveillance to cumulative dose and radiotherapy field. Survivors frequently cannot obtain either, so the guidelines are unusable even where someone is willing to follow them.","summary":"The Children's Oncology Group Long-Term Follow-Up Guidelines and their harmonised international equivalents are indexed by exposure: this cumulative anthracycline dose implies this echocardiogram interval, this radiotherapy field implies this surveillance. The guidelines are good. The input is missing. Survivors frequently do not have their radiotherapy fields and doses recorded anywhere they can reach, and the commonest failure in revaccination after transplant is that neither the centre nor the general practice believes the schedule is theirs.\n\nWhat is proposed is narrow and technical: a structured exposure record generated automatically from the treatment system at the end of treatment, containing cumulative doses by agent, radiotherapy fields and doses, surgical procedures and transplant conditioning, in a format another system can query. From that, the due surveillance for any given year can be computed rather than looked up, which is what turns a guideline into a reminder.\n\nThis is deliberately not a survivorship care plan. That instrument was mandated and then failed its randomised trials, and the 2018 review's recommendation was to focus on whether the recommendations in a plan are subsequently acted on. A document is read once; a machine-readable exposure record can be queried every year by whoever is looking after the person, which is a different thing with a different failure mode.","asOf":"2026-10-02","links":[{"label":"Landier et al., Development of risk-based guidelines for pediatric cancer survivors: the Children's Oncology Group Long-Term Follow-Up Guidelines (JCO 2004;22:4979-4990)","url":"https://doi.org/10.1200/JCO.2004.11.032"},{"label":"Jacobsen et al., Systematic review of the impact of cancer survivorship care plans on health outcomes and health care delivery (JCO 2018;36:2088-2100)","url":"https://doi.org/10.1200/JCO.2018.77.7482"},{"label":"Children's Oncology Group Long-Term Follow-Up Guidelines","url":"http://www.survivorshipguidelines.org/"}],"tags":["rejuvenation","survivorship","open-problem","data","follow-up"],"related":["rejuv-paed-cog-ltfu-guidelines","rejuv-paed-transition-to-adult-care","rejuv-tx-long-term-follow-up-frameworks","survivorship-care-plan","idea-acc-auto-generated-survivorship-plans","idea-acc-aya-survivorship-passport","ighg","rejuvenation-roadmap"],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["rejuv-agenda-nobody-owns-the-follow-up","rejuv-agenda-late-effects-are-not-counted","b-data-silos","b-care-fragmentation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A structured, machine-readable exposure record generated at the end of treatment increases the proportion of survivors who receive the surveillance their exposures imply, which a document handed over at discharge did not.","rationale":"Risk-based guidelines exist and are not followed: the largest survey of its kind concluded that the majority of childhood cancer survivors do not receive recommended risk-based care, and 94 per cent of physicians reported unmet information needs about survivors' late-effect risks. The 2018 systematic review of survivorship care plans found little evidence of benefit and recommended that research move to whether recommendations are acted on. The missing component in both findings is a queryable exposure record.","test":"Implement automatic exposure-record generation in one cancer centre's treatment system, feed computed surveillance reminders to the survivor and their general practitioner, and measure guideline-concordant surveillance against a matched comparison centre at two and five years.","maturity":"early-clinical","actor":"data","cost":"medium","horizonYears":5},{"id":"idea-immunotherapy-mss-crc","kind":"idea","name":"Making microsatellite-stable colorectal cancer immunotherapy-responsive","aka":[],"tldr":"Ninety-five percent of bowel cancers ignore immunotherapy. Combinations that heat the tumour up (targeted drugs, radiation, new checkpoints) are the main hope.","summary":"MSS CRC has few neoantigens, TGF-beta-rich stroma, and liver metastases that induce systemic tolerance. Approaches: botensilimab + balstilimab (Fc-enhanced anti-CTLA-4; 17% ORR in the phase 1, 21% in the later cohort selected for the absence of liver metastases), KRAS G12C inhibitor + PD-1, anti-EGFR + PD-1 in RAS wild-type (AVETUX), radiation to liver metastases, CEA-directed T-cell engagers.","asOf":"2026-09-07","links":[{"label":"Bullock et al., Botensilimab plus balstilimab in relapsed or refractory microsatellite-stable colorectal cancer (Nature Medicine 2024)","url":"https://doi.org/10.1038/s41591-024-03083-7"}],"tags":[],"related":["colorectal-roadmap","idea-crc-mss-immunotherapy-by-biomarker-not-by-line"],"cancers":["colorectal"],"sections":[],"technologies":["checkpoint-inhibitor","kras-inhibitors"],"targets":["ctla4","pd1","kras"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["cold-vs-hot","msi"],"trials":["checkmate-8hw","codebreak-300","keynote-177","nct05855200","nct05890742"],"people":[],"bottlenecks":[],"keyPapers":["paper-bullock-botensilimab-balstilimab-mss-colorectal-nat-med-2024","paper-topalian-anti-pd1-nejm-2012","paper-le-mmr-deficiency-pd1-nejm-2015","paper-ctla-4-colorectal-j-exp-clin-cancer-res-2019"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Fc-enhanced CTLA-4 blockade plus PD-1 blockade, restricted to MSS CRC without active liver metastases, will show an OS benefit over trifluridine/tipiracil-based therapy in third line.","rationale":"Liver metastases deplete tumour-specific CD8 T cells; excluding them enriches for responders, as seen in the botensilimab expansion cohorts.","test":"Randomised phase 3 in third-line MSS CRC without liver metastases (BATTMAN-style), OS primary; ctDNA and TGF-β signatures as stratifiers.","maturity":"early-clinical"},{"id":"idea-prev-interval-cancer-audit-blood-tests","kind":"idea","name":"Mandatory interval-cancer audit for every blood-based screening test","aka":[],"tldr":"When a screening test misses a cancer, we should know. Linking every negative result to the cancer registry and publishing what was missed, by stage, should be a condition of use.","summary":"Cervical and breast programmes audit interval cancers routinely; commercial blood tests do not. Propose that authorisation or reimbursement for MCED and single-cancer blood tests requires registry linkage of all negatives, with annual publication of stage-specific sensitivity, interval cancer rates, and test-negative cancers by subtype.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The hardest cancers are found late): Crosby et al., Early detection of cancer (Science 2022)","url":"https://doi.org/10.1126/science.aay9040"}],"tags":[],"related":["seer"],"cancers":[],"sections":["early-detection"],"technologies":["liquid-biopsy","mced"],"targets":[],"drugs":["shield","galleri"],"companies":[],"institutions":[],"pathways":[],"terms":["real-world-evidence"],"trials":[],"people":[],"bottlenecks":["b-early-detection","b-biomarker-validation","b-real-world-evidence"],"keyPapers":["paper-crosby-science"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Registry-linked audit will reveal real-world stage I sensitivity materially below case-control estimates for at least some cancers, and will change which tests payers cover.","rationale":"Case-control designs overstate sensitivity through spectrum bias; only prospective negatives tell the truth. The audit is cheap where registries exist.","test":"Pilot with one approved test (e.g. Shield for colorectal cancer) in a state with a complete registry; publish the two-year interval cancer rate.","maturity":"speculative","actor":"regulator","cost":"small","horizonYears":2},{"id":"idea-fund-cross-funder-portfolio-registry","kind":"idea","name":"Mandatory machine-readable portfolio reporting for all large cancer funders","aka":[],"tldr":"Every funder that spends more than $50 million a year on cancer research would publish what it funds in a shared, coded database, so gaps and duplication can be seen across the whole system.","summary":"The International Cancer Research Partnership already codes members' portfolios by cancer type and Common Scientific Outline category, but participation is voluntary and misses most industry-funded academic work, Chinese funders and a large part of European funding. Governments and umbrella bodies would require reporting as a condition of charitable tax status or public co-funding, with a common ontology, award-level data and outputs linked (publications, trials, patents). Coverage is what turns a nice database into a planning tool.","asOf":"2026-09-08","links":[{"label":"International Cancer Research Partnership","url":"https://www.icrpartnership.org/"}],"tags":[],"related":["idea-fund-burden-weighted-portfolio","idea-fund-dollars-per-death-dashboard"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["cruk","nci","dkfz"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-funding-allocation","b-data-silos"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Raising portfolio-registry coverage above 80% of global non-industry cancer research spend enables at least three documented cases per year where funders reallocate or co-fund to fill identified gaps or eliminate duplication.","rationale":"Coded portfolio analysis has already exposed funding imbalances in the UK and US; the missing piece is coverage and enforcement. Clinical trial registration went from voluntary and patchy to near-universal once journals and regulators made it mandatory.","test":"One country mandates reporting for two years; measure coverage, the number of gap analyses produced and documented reallocation decisions citing the registry.","maturity":"speculative","actor":"data","cost":"small","horizonYears":2},{"id":"idea-acc-national-virtual-mdt-rare-complex","kind":"idea","name":"Mandatory national virtual tumour boards for rare and complex cancers","aka":[],"tldr":"A patient with a rare cancer treated at a small hospital should have their case reviewed by the national experts by video before treatment starts. Make that referral automatic.","summary":"Outcomes for sarcoma, rare gynaecological tumours, and other uncommon cancers depend heavily on expert review before surgery, yet patients at smaller hospitals are often treated locally without it. National virtual multidisciplinary boards, with mandatory pre-treatment referral for a defined list of diagnoses and a turnaround guarantee, have been implemented for sarcoma in several countries. Extending the model with a legal or reimbursement mandate would standardise access.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Fragmented care and guideline gaps): Hanna et al., Mortality due to cancer treatment delay: systematic review and meta-analysis (BMJ 2020)","url":"https://doi.org/10.1136/bmj.m4087"}],"tags":[],"related":[],"cancers":["sarcoma","neuroendocrine"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-care-fragmentation","b-rare-cancers"],"keyPapers":["paper-hanna-bmj"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Mandatory national virtual review for listed rare cancers will increase the proportion treated according to expert recommendation from under 50% to above 85% and improve margin-negative resection rates.","rationale":"Centralised expertise with decentralised delivery is the accepted model for rare disease; the internet removes the geographic excuse.","test":"Implement nationwide with a registry comparison of concordance, resection quality, and survival before and after the mandate.","maturity":"being-tested-at-scale","actor":"policy","cost":"small","horizonYears":2},{"id":"idea-data-ai-post-market-performance-reporting","kind":"idea","name":"Mandatory post-market performance reporting for cancer AI","aka":[],"tldr":"Once an AI tool is in use, its maker and the hospital would have to report regularly how it is actually performing on real patients, and the reports would be public.","summary":"Post-market surveillance of medical devices focuses on adverse events, not performance. For AI, the relevant harm is silent degradation. The proposal requires deployed cancer AI to report standardised performance metrics (sensitivity, specificity, calibration, subgroup results, override rates) per site quarterly to the model registry, with thresholds that trigger regulator review, analogous to pharmacovigilance periodic safety update reports.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (AI that is built but not validated or deployed): Wu et al., How medical AI devices are evaluated: limitations and recommendations from an analysis of FDA approvals (Nature Medicine 2021)","url":"https://doi.org/10.1038/s41591-021-01312-x"}],"tags":[],"related":["idea-data-clinical-ai-model-registry"],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-ai-validation"],"keyPapers":["paper-wu-nat-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Mandatory performance reporting will detect clinically significant performance degradation in a meaningful share of deployed models within their first two years, which would otherwise have gone unnoticed.","rationale":"Studies of deployed models (for example sepsis prediction tools) found real-world performance far below published claims, discovered only by independent academic audits; systematic reporting would make this routine.","test":"Require quarterly reports for all AI in one national screening programme for two years; count detected degradations and actions taken.","maturity":"speculative","actor":"regulator","cost":"medium","horizonYears":3},{"id":"idea-reg-vein-to-vein-public-benchmark","kind":"idea","name":"Mandatory public reporting of vein-to-vein time and failure rate per CAR-T product","aka":[],"tldr":"Patients and doctors cannot see how long each CAR-T maker takes or how often manufacturing fails. Publishing this would create pressure to get faster and more reliable.","summary":"Vein-to-vein times for commercial CAR-T range from roughly three to eight weeks and out-of-specification rates from a few percent to over ten, but these figures appear only in trial publications and investor slides. The proposal is a regulatory condition that each approved cell therapy reports, quarterly and publicly, median and 90th percentile apheresis-to-infusion time, out-of-specification and manufacturing failure rates, and the proportion of enrolled patients never infused, stratified by country.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Manufacturing cost and time for living and radioactive medicines): Hernandez, Prasad & Gellad, Total costs of chimeric antigen receptor T-cell immunotherapy (JAMA Oncology 2018)","url":"https://doi.org/10.1001/jamaoncol.2018.0977"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["car-t"],"targets":[],"drugs":["axicabtagene-ciloleucel","ciltacabtagene-autoleucel"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-manufacturing-cell-therapy","b-real-world-evidence"],"keyPapers":["paper-hernandez-jama-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Public benchmarking is followed by a fall in median vein-to-vein time of at least a week across the market within two years and convergence of failure rates towards the best performer.","rationale":"Public reporting of hospital outcomes and airline punctuality changed behaviour where private reporting did not. Manufacturers already collect these data for their own control; publication is cheap.","test":"Begin with voluntary reporting through a registry such as CIBMTR or EBMT, publish two years of data, and evaluate whether times and failure rates changed relative to the prior period.","maturity":"speculative","actor":"regulator","cost":"small","horizonYears":2},{"id":"idea-prev-radon-testing-at-property-sale","kind":"idea","name":"Mandatory radon testing when homes are sold, with subsidised mitigation","aka":[],"tldr":"Radon gas from the ground is the second biggest cause of lung cancer. Testing every home at sale and paying for fixes in high-radon areas would prevent thousands of cases.","summary":"Radon gas from the ground is the second biggest cause of lung cancer, yet testing is voluntary and rare, so this idea mandates radon testing when homes are sold in high-radon zones and subsidises mitigation. Point-of-sale mandates already work for energy efficiency certificates, and mitigation is cheap and effective. The aim is to halve the proportion of homes above the action level in high-radon areas within ten years, evaluated by measured indoor radon distributions and modelled lung cancers averted. The test is adoption in one region with radon levels and mitigation rates compared against controls. Speculative in maturity, it addresses the bottleneck Prevention we already have is not deployed and links to NSCLC.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Prevention we already have is not deployed): Islami et al., Proportion of cancer attributable to modifiable risk factors (CA 2018)","url":"https://doi.org/10.3322/caac.21440"}],"tags":[],"related":[],"cancers":["nsclc"],"sections":["prevention"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption"],"keyPapers":["paper-islami-ca-cancer-j-clin"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Mandatory testing at sale plus subsidies halves the proportion of homes above the action level in high-radon areas within ten years.","rationale":"Point-of-sale mandates work for energy efficiency certificates; mitigation is cheap and effective.","test":"Adopt in one region; compare radon levels and mitigation rates with controls.","maturity":"speculative","actor":"policy","cost":"medium","horizonYears":8},{"id":"idea-data-excluded-populations-rwe-mandate","kind":"idea","name":"Mandatory real-world reporting for patients excluded from pivotal trials","aka":[],"tldr":"Older, frailer and sicker patients are usually kept out of trials but make up most of those treated. Require companies to report how these patients do in practice.","summary":"Pivotal trials exclude patients over 75, with poor performance status, organ dysfunction, brain metastases or HIV, yet these groups receive the drug after approval. The proposal is a post-marketing requirement: within two years of approval, sponsors report real-world effectiveness and toxicity in pre-specified excluded subgroups using structured registry data, with results added to the label.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Weak real-world evidence and registries): Gyawali, Hey & Kesselheim, Assessment of the clinical benefit of cancer drugs receiving accelerated approval (JAMA Intern Med 2019)","url":"https://doi.org/10.1001/jamainternmed.2019.0462"}],"tags":[],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["real-world-evidence","geriatric-assessment"],"trials":[],"people":[],"bottlenecks":["b-real-world-evidence","b-aging-comorbidity","b-trial-diversity"],"keyPapers":["paper-gyawali-jama-intern-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Mandated reporting will reveal clinically meaningful differences in toxicity or benefit in excluded populations for a substantial share of new approvals, changing prescribing in those groups.","rationale":"Real-world studies of checkpoint inhibitors in performance status 2 patients found survival far below trial results; such findings currently depend on academic interest rather than requirement.","test":"Retrospectively produce excluded-population reports for ten recent approvals using existing federated data; measure how often the findings would have changed guideline recommendations.","maturity":"speculative","actor":"regulator","cost":"medium","horizonYears":3},{"id":"idea-fund-device-technique-registry","kind":"idea","name":"Mandatory staged registries for new surgical techniques before wide adoption","aka":[],"tldr":"New operations and surgical devices spread by enthusiasm before evidence, as robotic prostatectomy, minimally invasive radical hysterectomy and HIPEC did. Every new cancer surgical technique would follow the IDEAL framework, with a prospective registry from first use, defined triggers for a randomised comparison, and payment conditional on registry participation until assessment is complete.","summary":"Regulators and payers require that new cancer surgical techniques and devices follow the IDEAL framework (idea, development, exploration, assessment, long-term study), with a prospective registry from first use, defined triggers for moving to a randomised comparison, and reimbursement conditional on registry participation until assessment is complete. Devices already need regulatory clearance but techniques need none, and both diffuse before evidence exists (robotic prostatectomy, minimally invasive radical hysterectomy, cytoreductive surgery with HIPEC). Registries also produce the learning-curve and volume data needed for credentialling.","asOf":"2026-09-08","links":[{"label":"IDEAL Collaboration","url":"https://www.ideal-collaboration.net/"},{"label":"ACS NSQIP","url":"https://www.facs.org/quality-programs/data-and-registries/acs-nsqip/"}],"tags":[],"related":["idea-fund-surgical-ai-robotics-evaluation","idea-fund-device-and-technique-translation-fund","idea-fund-surgical-video-registry","prostate-roadmap","idea-prostate-per-lesion-mri-audit-before-focal-treatment"],"cancers":["cervical","prostate","colorectal"],"sections":[],"technologies":["robotic-surgery","hipec","hifu-histotripsy"],"targets":[],"drugs":[],"companies":["intuitive-surgical"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-surgery-radiation-innovation","b-real-world-evidence"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Mandatory staged registries reduce the time from first use to a randomised or IDEAL stage 3 comparison for new cancer surgical techniques from more than a decade to under five years, and detect harmful diffusion (as with minimally invasive radical hysterectomy) before it becomes standard.","rationale":"The LACC trial found worse survival with minimally invasive radical hysterectomy after the technique had spread for years without randomised evidence; national joint replacement registries have detected failing implants years before regulators. Coverage-with-evidence-development has worked for several devices in the US and UK.","test":"Pilot in one country for three new techniques or devices, measuring registry completeness, time to comparative evidence and the frequency of adoption decisions changed by registry data.","maturity":"early-clinical","actor":"regulator","cost":"medium","horizonYears":3},{"id":"idea-data-subgroup-performance-reporting-mandate","kind":"idea","name":"Mandatory subgroup performance reporting for cancer AI","aka":[],"tldr":"Every AI tool would have to report how well it works for women and men, different ethnic groups, ages, scanner types and hospitals, not just an overall score.","summary":"Cancer AI is often validated on populations that do not match deployment populations; performance gaps by skin tone (dermatology), breast density, ethnicity and scanner vendor are documented. The proposal requires, for clearance and in the model registry, performance reporting across a standard set of subgroups with minimum sample sizes and confidence intervals, and labelling restrictions where performance is unknown or inadequate.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (AI that is built but not validated or deployed): Wu et al., How medical AI devices are evaluated: limitations and recommendations from an analysis of FDA approvals (Nature Medicine 2021)","url":"https://doi.org/10.1038/s41591-021-01312-x"}],"tags":[],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":["dermoscopy-ai","mammography"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-ai-validation","b-trial-diversity"],"keyPapers":["paper-wu-nat-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Mandatory subgroup reporting will reveal clinically meaningful performance disparities in a substantial share of cleared cancer AI and lead to label restrictions or retraining for those models.","rationale":"Pulse oximetry's racial bias went unrecognised for decades because subgroup performance was not required; AI will repeat this at scale unless reporting is mandatory.","test":"Evaluate ten cleared cancer AI devices on the standard subgroup set using sequestered data; publish disparities; track subsequent label changes.","maturity":"speculative","actor":"regulator","cost":"small","horizonYears":2},{"id":"idea-reg-manufacturing-change-passport","kind":"idea","name":"Manufacturing-change passport: one approved CMC change accepted everywhere in 30 days","aka":[],"tldr":"Changing how a cancer drug is made must be approved separately in over a hundred countries, which takes years and causes shortages. One approval should count for all.","summary":"Post-approval chemistry, manufacturing and controls changes (new site, new supplier, process improvement) take three to five years to be approved worldwide because each country reviews them separately; manufacturers therefore delay improvements and keep obsolete processes running. ICH Q12 provides tools for managed change but adoption is uneven. The proposal is a reliance passport: a CMC change approved by any WHO-listed authority is deemed approved by participating regulators 30 days after notification unless they object with reasons.","asOf":"2026-09-08","links":[{"label":"ICH quality guidelines (Q12)","url":"https://www.ich.org/page/quality-guidelines"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":["carboplatin"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-regulatory-fragmentation","b-manufacturing-cell-therapy"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Passport adoption cuts the time to global implementation of a CMC change for oncology medicines from a median above three years to under six months, and reduces the number of oncology drug shortages attributed to manufacturing changes.","rationale":"CMC changes are assessed against the same pharmacopoeial and comparability standards everywhere; duplicate review adds time but not safety. Shortages of platinum chemotherapy in 2023 were prolonged by the inability to switch or add sites quickly.","test":"Pilot among Access Consortium and Orbis members on 50 CMC changes for oncology products; measure time to global implementation and any post-change quality defects against matched historical changes.","maturity":"early-clinical","actor":"regulator","cost":"small","horizonYears":3},{"id":"idea-metabolic-vulnerability-mapping","kind":"idea","name":"Map metabolic dependencies in the patient, not the dish","aka":[],"tldr":"Metabolic drugs keep failing because tumours switch fuels. Measuring what a patient's tumour actually eats, with tracers and PET, could pick the right metabolic drug for the right tumour.","summary":"This idea proposes mapping metabolic dependencies in the patient rather than the dish: tumours switch fuels, so measuring what a tumour consumes with PET tracers could match drug to tumour. Isotope tracing in patients (DeBerardinis) shows in vivo fuel use differs from culture, FDG, glutamine (18F-FGln) and acetate tracers exist, and glutaminase inhibitors failed in unselected populations. The hypothesis is that tracer-defined phenotypes (glycolytic, glutamine- or lipid-dependent) predict response to matched inhibitors, because imaging reads tumour metabolism non-invasively. The test is a basket trial assigning therapy by baseline 18F-FGln and FDG PET in Non-small-cell lung cancer, Renal cell carcinoma and Glioma & glioblastoma (Cancer metabolism pathway).","asOf":"2026-09-08","links":[{"label":"Faubert et al., Lactate metabolism in human lung tumours (Cell 2017)","url":"https://doi.org/10.1016/j.cell.2017.09.019"}],"tags":["mechanism","open-question"],"related":[],"cancers":["nsclc","rcc","glioblastoma"],"sections":[],"technologies":["fdg-pet","pet"],"targets":[],"drugs":[],"companies":[],"institutions":["mskcc","md-anderson"],"pathways":["cancer-metabolism","keap1-nrf2"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-faubert-cell"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Tracer-defined metabolic phenotypes (glycolytic, glutamine-dependent, lipid-dependent) predict response to matched metabolic inhibitors, rescuing agents that failed in unselected trials.","rationale":"Tumour metabolism is heterogeneous and plastic; imaging can read it non-invasively and repeatedly.","test":"Basket trial with baseline 18F-FGln and FDG PET assigning glutaminase inhibitor or glycolysis-targeting agent, with PET flux change at 2 weeks as pharmacodynamic endpoint.","maturity":"preclinical-evidence"},{"id":"idea-data-trial-to-registry-bridge","kind":"idea","name":"Map trial case report forms to the registry standard so trial and routine data join","aka":[],"tldr":"Trials and hospital records describe the same things in different languages. Publish the translation so trial patients can be followed for life in routine data and trial results compared with routine care.","summary":"Clinical trial data follow CDISC standards; routine data follow mCODE or OMOP. Formal, maintained mappings (CDISC to mCODE, CDISC to OMOP) would allow trial participants to be followed via registries after the trial ends, trial cohorts to be compared with matched real-world cohorts, and completed trial datasets to be pooled with routine data. CDISC and HL7 have a joint project; the proposal funds it to completion and requires sponsors to deliver the mapped dataset alongside submissions.","asOf":"2026-09-08","links":[{"label":"CDISC","url":"https://www.cdisc.org/"}],"tags":[],"related":["clinicaltrials-gov"],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-data-silos","b-real-world-evidence","b-trial-design"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Mapped trial datasets will enable long-term follow-up of more than 80 percent of participants via registries at less than a tenth of the cost of active follow-up, and permit trial-versus-real-world comparisons for every new approval within a year.","rationale":"Long-term follow-up is the most expensive part of many trials and the reason late toxicities and late relapses are under-documented; registries already hold the information.","test":"Map three completed phase 3 datasets to mCODE, link to a national registry, and compare registry-derived survival with trial-recorded survival; measure agreement and cost.","maturity":"speculative","actor":"regulator","cost":"small","horizonYears":3},{"id":"idea-bio1-spatial-clone-immune-map","kind":"idea","name":"Map which tumour clones sit next to which immune cells before choosing therapy","aka":[],"tldr":"New imaging shows where every cell type sits in a tumour slice. Using it to see which sub-populations are hidden from immune cells could explain why immunotherapy fails in parts of a tumour.","summary":"Spatial transcriptomics and multiplex imaging can now assign genotype-inferred clones and immune phenotypes to positions in a section. The proposal is a diagnostic-biopsy pipeline reporting clone-immune neighbourhoods: which subclones are immune-excluded, which express MHC, and whether resistant clones cluster in immune deserts. This would be used to decide whether to combine a targeted agent with immunotherapy or a stroma-modifying agent.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Tumour heterogeneity and clonal evolution): Gerlinger et al., Intratumor heterogeneity and branched evolution (NEJM 2012)","url":"https://doi.org/10.1056/NEJMoa1113205"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["single-cell-spatial","digital-pathology-ai"],"targets":[],"drugs":[],"companies":["10x-genomics"],"institutions":[],"pathways":[],"terms":["cold-vs-hot","tils"],"trials":[],"people":[],"bottlenecks":["b-tumor-heterogeneity","b-immunotherapy-response"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Tumours in which the dominant resistant subclone occupies an immune-excluded niche progress on immunotherapy combinations at a higher rate than tumours with immune-infiltrated resistant subclones, and this is measurable at baseline.","rationale":"Heterogeneity is spatial as well as genetic; immune exclusion is a local property. Current bulk PD-L1 or TMB scores erase both dimensions.","test":"Retrospective spatial profiling of 200 pre-treatment biopsies from immunotherapy trials with known outcomes; prospective validation if the neighbourhood score adds to PD-L1 and TMB.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":4},{"id":"idea-bio1-clone-to-lesion-mapping","kind":"idea","name":"Match each blood-detected clone to the lesion it comes from on the scan","aka":[],"tldr":"Blood tests tell you which tumour sub-populations are growing; scans tell you which lesions are growing. Joining the two would tell you where to biopsy or irradiate.","summary":"Tissue-of-origin methylation, lesion-specific private mutations from multi-site biopsies, and lesion volume kinetics from serial imaging could be combined in a joint model that assigns plasma clone fractions to anatomical lesions. This would let clinicians direct local therapy at the lesion carrying the expanding resistant clone without biopsying every site.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Tumour heterogeneity and clonal evolution): Gerlinger et al., Intratumor heterogeneity and branched evolution (NEJM 2012)","url":"https://doi.org/10.1056/NEJMoa1113205"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["liquid-biopsy","pet-ct","whole-body-mri","methylation-profiling"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-tumor-heterogeneity","b-metastasis-biology"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A joint ctDNA-imaging model localises the source lesion of an emerging resistant clone correctly in most cases when validated against multi-site biopsy or autopsy.","rationale":"Lesion-level heterogeneity is the norm in metastatic disease; ctDNA is lesion-agnostic and imaging is genotype-agnostic. The two are rarely modelled together.","test":"Retrospective model building on rapid autopsy cases with serial plasma and imaging in life; prospective validation in patients undergoing multi-site biopsy at progression.","maturity":"speculative","actor":"data","cost":"small","horizonYears":4},{"id":"idea-bio2-caf-subtype-assignment","kind":"idea","name":"Match therapy to the type of scar-forming cell in the tumour","aka":[],"tldr":"The support cells that build a tumour's scaffolding come in several types: some protect the tumour, others restrain it. Treating all of them the same way explains past failures.","summary":"Attempts to strip tumour stroma wholesale, including hyaluronidase in pancreatic cancer and hedgehog inhibition, failed or worsened outcomes, consistent with the finding that some fibroblast subsets restrain tumour growth. Human single-cell and spatial atlases now define myofibroblastic, inflammatory and antigen-presenting fibroblast states. A classifier that assigns patients to stroma-directed treatment by subtype, rather than by disease, is the logical next step.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Cold tumours and the immunosuppressive microenvironment): Haslam & Prasad, Estimation of the percentage of US patients eligible for and responding to checkpoint inhibitors (JAMA Netw Open 2019)","url":"https://doi.org/10.1001/jamanetworkopen.2019.2535"}],"tags":[],"related":[],"cancers":["pancreatic","colorectal"],"sections":[],"technologies":["single-cell-spatial","digital-pathology-ai","rna-seq"],"targets":["fap"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["desmoplasia","cms-subtypes"],"trials":[],"people":["erik-sahai"],"bottlenecks":["b-tme-immunosuppression","b-negative-results","b-biomarker-validation"],"keyPapers":["paper-haslam-jama-netw-open"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A validated fibroblast-subtype classifier predicts which patients benefit from stroma-directed therapy, and pooling all subtypes together dilutes an effect that exists only in the myofibroblastic-dominant subgroup.","rationale":"Hedgehog inhibition accelerated pancreatic cancer in mice by depleting restraining stroma, a clear demonstration that stromal identity determines direction of effect. Subtype-guided assignment turned negative results into positive ones in breast cancer and in colorectal consensus subtypes.","test":"Reanalyse tissue from failed stroma-targeting trials by fibroblast subtype for a retrospective interaction test; if positive, run a prospective subtype-selected trial.","maturity":"speculative","actor":"research","cost":"medium","horizonYears":7},{"id":"idea-acc-pain-control-public-audit","kind":"idea","name":"Measure and publish pain control rates in every cancer centre","aka":[],"tldr":"Hospitals publish survival and infection rates but almost never how many of their cancer patients are in uncontrolled pain. Measuring and publishing it would make pain a priority.","summary":"Undertreated cancer pain remains common even in well-resourced systems. Routine pain scoring exists in many hospitals but is not aggregated, benchmarked, or published. A national quality indicator (for instance, the proportion of patients with advanced cancer reporting moderate or severe pain at outpatient visits) with public reporting by centre would use the same accountability lever that improved infection control and waiting times.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Pain relief and palliative care are unavailable to most): WHO fact sheet, Palliative care","url":"https://www.who.int/news-room/fact-sheets/detail/palliative-care"}],"tags":[],"related":[],"cancers":[],"sections":["supportive-care"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-palliative","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Centres subject to public pain-control reporting will reduce the proportion of patients with moderate or severe pain by at least a third within two years.","rationale":"Public reporting of simple, patient-relevant indicators changes institutional priorities; pain is measurable, common, and treatable.","test":"Pilot a national indicator with public reporting in one country and compare pain prevalence trends with a comparator without reporting.","maturity":"speculative","actor":"policy","cost":"small","horizonYears":2},{"id":"idea-moon-cognitive-toxicity-programme","kind":"idea","name":"Measure and treat chemo brain with objective digital cognitive testing","aka":[],"tldr":"Many people report thinking and memory problems after cancer treatment. Measure it properly with short phone-based tests and run trials of treatments.","summary":"Cancer-related cognitive impairment is common, under-recognised and lacks validated treatments; assessment relies on lengthy neuropsychological batteries. Smartphone-based cognitive tests can capture trajectories cheaply. The proposal is a programme pairing digital cognitive monitoring in trials and clinics with a platform trial of interventions (exercise, cognitive rehabilitation, methylphenidate, memantine, sleep interventions) and biological correlates (inflammatory markers, imaging).","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Toxicity and quality of life are undervalued): Di Maio et al., Symptomatic toxicities experienced during anticancer treatment: agreement between patient and physician reporting (JCO 2015)","url":"https://doi.org/10.1200/JCO.2014.57.9334"}],"tags":[],"related":[],"cancers":[],"sections":["rejuvenation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol","b-survivorship"],"keyPapers":["paper-di-maio-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Digital testing detects clinically meaningful cognitive decline in at least a quarter of patients on common regimens, and at least one intervention improves objective and patient-reported cognition at six months.","rationale":"Measurement is the bottleneck; once cognition is routinely measured it becomes a target for drugs and dosing decisions, as fatigue and nausea did.","test":"Embed digital cognitive testing in three cooperative-group trials; run a four-arm intervention platform in survivors with measured impairment.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":4},{"id":"idea-tr1-therapeutic-drug-monitoring-for-oral-tkis","kind":"idea","name":"Measure blood levels of oral targeted drugs and adjust doses to a target range","aka":[],"tldr":"Blood levels of oral cancer pills vary several-fold between people on the same dose, so some are under-treated and others poisoned. Checking levels and adjusting the dose, as is routine for some antibiotics, could fix both.","summary":"Therapeutic drug monitoring (TDM) for oral kinase inhibitors and hormonal agents with established exposure-response relationships and high inter-patient variability (imatinib, sunitinib, pazopanib, abiraterone, tamoxifen via endoxifen, and newer agents), with dose adjustment to a target trough. Dutch multicentre TDM studies have shown feasibility and increased target attainment; outcome-powered randomised trials are lacking.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Wrong doses): FDA Oncology Center of Excellence, Project Optimus","url":"https://www.fda.gov/about-fda/oncology-center-excellence/project-optimus"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["kinase-inhibitors","endocrine-therapy"],"targets":[],"drugs":["imatinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-dose-optimisation","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"TDM-guided dosing will increase the proportion of patients within the target exposure range from roughly half to over 80 percent and will improve PFS or reduce grade 3+ toxicity relative to fixed dosing in a randomised comparison.","rationale":"Adherence, food, interactions and pharmacogenetics cause large exposure variability; fixed dosing ignores it. TDM is standard for narrow-therapeutic-index drugs in other fields.","test":"A randomised trial of TDM-guided versus fixed dosing for two or three TKIs with the strongest exposure-response evidence, with PFS and toxicity endpoints.","maturity":"early-clinical","actor":"clinic","cost":"small","horizonYears":3},{"id":"idea-lung-brain-metastasis-prevention-as-a-primary-endpoint","kind":"idea","name":"Measure brain metastasis prevention as a primary endpoint, not as a secondary one","aka":[],"tldr":"Lung cancer spreads to the brain more than any other common cancer, and the newest drugs seem to stop it happening. Almost no trial is designed to prove that, so the claim stays a footnote.","summary":"Prophylactic cranial irradiation is the proof of principle: Aupérin's overview of 987 patients showed that treating a brain with no visible disease in it extends life in small-cell lung cancer. In non-small-cell disease, alectinib, lorlatinib and osimertinib all appear to prevent as well as treat central nervous system disease, and CROWN's intracranial response figures and ALINA's central nervous system disease-free survival are the strongest evidence for it. But these are secondary endpoints, measured with inconsistent imaging schedules, in trials powered for something else.\n\nThe idea is to design for it: brain-metastasis-free survival as a primary endpoint, with protocol-mandated MRI at fixed intervals, in the populations where the risk is highest. Prevention of brain metastases is a distinct clinical good, and the current evidence base does not let anyone say by how much any drug delivers it.","asOf":"2026-09-25","links":[],"tags":["lung-evidence"],"related":["idea-bio2-brain-met-prevention-trials","idea-tr1-brain-mets-default-included","idea-fund-brain-metastases-programme","lung-cancer-evidence-roadmap"],"cancers":["lung-cancer","nsclc","sclc","alk-positive-nsclc","egfr-mutant-nsclc"],"sections":["targeted-therapy","radiation"],"technologies":["stereotactic-radiosurgery","radiotherapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["brain-metastases","prophylactic-cranial-irradiation"],"trials":[],"people":[],"bottlenecks":["b-brain-delivery","b-trial-design","b-toxicity-qol","b-metastasis-biology"],"keyPapers":["paper-auperin-prophylactic-cranial-irradiation-sclc-nejm-1999","paper-shaw-crown-lorlatinib-crizotinib-nejm-2020","paper-peters-alex-alectinib-crizotinib-nejm-2017","paper-wu-alina-adjuvant-alectinib-nejm-2024"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"In driver-positive non-small-cell lung cancer, a central-nervous-system-penetrant inhibitor given from diagnosis reduces the cumulative incidence of brain metastases compared with a non-penetrant one, by an amount large enough to justify choosing between drugs on that basis and to change quality of life and cognitive outcomes.","rationale":"Brain metastases are the dominant failure pattern in ALK-positive and EGFR-mutant disease treated with first-generation inhibitors, and the main reason patients receive whole-brain radiotherapy with its cognitive cost. The prophylactic cranial irradiation precedent shows pre-emptive treatment of the sanctuary site can extend life. Drugs designed for brain penetration already exist, so this is a trial design problem rather than a drug discovery problem.","test":"Randomised trials in driver-positive disease with brain-metastasis-free survival as a primary endpoint and protocol-mandated MRI every three months, including patients with treated and asymptomatic central nervous system disease rather than excluding them, and with a cognitive and quality-of-life co-primary. Also a regulatory step: accepting brain-metastasis-free survival as a registrable endpoint.","maturity":"early-clinical","actor":"regulator","cost":"large","horizonYears":6},{"id":"lymphoma-ev-late-effects-of-the-treatments-given-now","kind":"idea","name":"Measure the late effects of the treatments being given now, not the ones given in 1975","aka":["Modern Hodgkin survivorship cohorts","Late effects of brentuximab, checkpoint inhibitors and CAR-T"],"tldr":"Everything known about the long-term cost of curing lymphoma comes from people treated decades ago with much larger radiation fields. Nobody knows the forty-year risks of what is given today.","summary":"The immune treatments make this more urgent, not less. Checkpoint inhibitors cause endocrine and autoimmune effects whose 20-year course is unknown; CAR-T carries prolonged cytopenias, hypogammaglobulinaemia and a second-malignancy signal that regulators have asked about; brentuximab vedotin causes peripheral neuropathy that can persist. The field is making de-escalation decisions on a harm estimate drawn from a treatment nobody gives any more.","asOf":"2026-10-01","links":[],"tags":["lymphoma-evidence"],"related":["lymphoma-roadmap"],"cancers":["hodgkin-lymphoma","early-stage-classical-hodgkin-lymphoma","advanced-stage-classical-hodgkin-lymphoma","dlbcl","non-hodgkin-lymphoma"],"sections":["supportive-care","radiation"],"technologies":["radiotherapy","imrt-igrt","proton-therapy","car-t","checkpoint-inhibitor"],"targets":[],"drugs":["brentuximab-vedotin","nivolumab","pembrolizumab","axicabtagene-ciloleucel","doxorubicin","procarbazine"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol","b-real-world-evidence","b-data-silos"],"keyPapers":["paper-schaapveld-second-cancer-risk-40-years-hodgkin-nejm-2015","paper-van-nimwegen-cardiovascular-disease-after-hodgkin-jama-intern-med-2015","paper-travis-breast-cancer-after-hodgkin-radiotherapy-jama-2003"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Prospective survivorship cohorts of patients treated with modern involved-site radiotherapy, brentuximab vedotin, checkpoint inhibitors and CAR-T will show a different late-effect profile from the historical cohorts, and knowing it will change how much de-escalation is worth pursuing.","rationale":"The Dutch cohorts, which set the terms of every Hodgkin de-escalation debate, enrolled patients treated between 1965 and 2000 with mantle fields; Travis measured breast cancer risk against doses up to and beyond 40 Gy. Modern involved-site radiotherapy delivers 20 Gy to a small volume, and the chemotherapy has changed completely. Schaapveld's most important finding is that second solid cancer incidence did not fall between the 1965 to 1976 and 1989 to 2000 treatment periods, which could mean that de-escalation so far has not helped, or that follow-up in the recent group is too short to tell. Only a cohort can distinguish those.","test":"Enrol consecutive patients treated for Hodgkin lymphoma and aggressive B-cell lymphoma from a defined date into a prospective cohort with linkage to cancer registries, cardiovascular records and fertility outcomes, with sufficient radiotherapy dosimetry and cumulative drug dose captured to support dose-response analysis at 10, 20 and 30 years. Report the first comparison against the historical cohorts at 15 years rather than waiting for 40.","maturity":"speculative","actor":"research","cost":"medium","horizonYears":15},{"id":"idea-bio2-histotripsy-immune-priming","kind":"idea","name":"Mechanically pulverise one tumour with ultrasound to wake the immune system","aka":[],"tldr":"Focused ultrasound can break a tumour apart without heat or cuts, leaving debris the immune system can learn from. Doing that to one tumour may help treat the rest.","summary":"Histotripsy destroys tissue mechanically through cavitation, is now approved for liver tumour destruction, and leaves antigenic debris and intact immune signals rather than the coagulated protein produced by thermal ablation. Mouse studies show abscopal effects and increased T-cell priming, and combination with checkpoint blockade is being explored in early trials.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Cold tumours and the immunosuppressive microenvironment): Haslam & Prasad, Estimation of the percentage of US patients eligible for and responding to checkpoint inhibitors (JAMA Netw Open 2019)","url":"https://doi.org/10.1001/jamanetworkopen.2019.2535"}],"tags":[],"related":[],"cancers":["hcc","colorectal"],"sections":[],"technologies":["hifu-histotripsy","thermal-ablation","checkpoint-inhibitor","irreversible-electroporation"],"targets":[],"drugs":[],"companies":["histosonics"],"institutions":[],"pathways":[],"terms":["abscopal-effect","immunogenic-cell-death"],"trials":[],"people":[],"bottlenecks":["b-tme-immunosuppression","b-surgery-radiation-innovation"],"keyPapers":["paper-haslam-jama-netw-open"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Histotripsy of a single index lesion plus checkpoint blockade produces higher rates of response in non-treated lesions than checkpoint blockade alone, with increased tumour-specific T-cell clones in blood.","rationale":"Unlike thermal ablation or radiotherapy, mechanical disruption preserves antigen structure and releases intact damage signals, giving a mechanistic reason to expect stronger priming. The device is already approved for liver lesions, so access is straightforward.","test":"A randomised phase 2 in liver-metastatic disease comparing checkpoint blockade with or without histotripsy of one lesion, with response in untreated lesions and blood T-cell receptor expansion as endpoints.","maturity":"early-clinical","actor":"clinic","cost":"medium","horizonYears":6},{"id":"idea-tr2-qsp-combo-dosing","kind":"idea","name":"Mechanistic computer models to pick combination doses before dosing patients","aka":[],"tldr":"Simulate how two drugs interact in the body and the tumour to pick a starting dose and schedule, instead of guessing from single-drug data.","summary":"Quantitative systems pharmacology models integrate pharmacokinetics, target engagement and downstream biology to predict combination effects and toxicities. FDA's model-informed drug development pathway accepts such models for dose justification. Making a QSP-based schedule proposal a standard component of combination investigational new drug applications would reduce empirical dose-escalation in combinations.","asOf":"2026-09-08","links":[{"label":"FDA model-informed drug development programme","url":"https://www.fda.gov/drugs/development-resources/model-informed-drug-development-paired-meeting-program"}],"tags":[],"related":["idea-tr2-combo-dose-matrix"],"cancers":[],"sections":[],"technologies":["ai-drug-design"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-combination-space","b-dose-optimisation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Combination trials whose dose and schedule were selected with a pre-specified QSP model will require fewer dose-escalation cohorts and reach recommended phase 2 dose with fewer dose-limiting toxicities than trials using conventional escalation.","rationale":"QSP models predicted the therapeutic window of several bispecifics and ADCs; overlapping toxicity in combinations is largely predictable from pharmacology.","test":"Retrospectively apply QSP dose selection to ten completed combination phase 1 trials and compare predicted with observed recommended doses; then run prospectively in five new trials.","maturity":"early-clinical","actor":"industry","cost":"medium","horizonYears":3},{"id":"idea-reg-patent-pool-oncology-eml","kind":"idea","name":"Medicines Patent Pool licences for every patented cancer drug on the WHO list","aka":[],"tldr":"Companies can license their patents to generic makers for poorer countries through a UN-backed pool, as happened for HIV. Only one cancer drug has been licensed so far; the whole essential list should be.","summary":"The Medicines Patent Pool signed its first oncology licence in 2022 (Novartis, nilotinib) covering a limited set of countries. Several patented oncology medicines are on the WHO Model List of Essential Medicines (and more will be added), including targeted therapies and checkpoint inhibitors, with generic and biosimilar manufacturers in India and China able to supply them. The proposal is a coordinated push, backed by the WHO and funders, for voluntary licences on all patented EML oncology medicines covering at least all low- and lower-middle-income countries, with technology transfer for biologics.","asOf":"2026-09-08","links":[{"label":"Medicines Patent Pool","url":"https://medicinespatentpool.org/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":["imatinib","osimertinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-drug-pricing","b-global-access"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Licensing brings generic or biosimilar versions of at least five patented EML oncology medicines to LMIC markets within four years at prices under 20% of originator prices, with measurable increases in treated patients.","rationale":"Voluntary licensing cut HIV drug prices by over 90% while preserving originator revenues in high-income markets; oncology's obstacles are commercial rather than legal, and reputational pressure plus assured quality through the pool has moved companies before.","test":"Negotiate licences for three additional products in two years; track time to generic availability, prices and volumes in licensed territories against unlicensed comparators.","maturity":"early-clinical","actor":"policy","cost":"small","horizonYears":4},{"id":"idea-menin-infant-all","kind":"idea","name":"Menin inhibitors for infant KMT2A-rearranged ALL","aka":[],"tldr":"Infant leukaemia is driven almost entirely by KMT2A fusions, which menin inhibitors were built to attack. Add them to the new blinatumomab-containing backbone.","summary":"Infant ALL EFS plateaued below 50% for two decades; blinatumomab (Interfant-21) is the first step forward. Revumenib is approved for KMT2Ar acute leukaemia including children ≥1 year and has paediatric formulation data; combining with chemotherapy and blinatumomab in the first year of life is the obvious next trial.","asOf":"2026-09-07","links":[{"label":"Issa et al., The menin inhibitor revumenib in KMT2A-rearranged or NPM1-mutant leukaemia (Nature 2023)","url":"https://doi.org/10.1038/s41586-023-05812-3"}],"tags":[],"related":[],"cancers":["all-leukemia","all-infant"],"sections":[],"technologies":[],"targets":["kmt2a","menin"],"drugs":["revumenib","ziftomenib","blinatumomab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["interfant-06","augment-101"],"people":[],"bottlenecks":[],"keyPapers":["paper-blinatumomab-all-leukemia-n-engl-j-med-2017","paper-blinatumomab-all-leukemia-lancet-oncol-2015","paper-blinatumomab-all-leukemia-j-clin-oncol-2011"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Adding a menin inhibitor to Interfant-21-type therapy raises 2-year EFS above 80% in KMT2A-rearranged infants without excess differentiation syndrome or hepatotoxicity.","rationale":"KMT2A fusion is the sole driver in most infant ALL; menin inhibition produces MRD-negative remissions in relapsed KMT2Ar leukaemia.","test":"International single-arm pilot then randomised addition of revumenib or ziftomenib to Interfant-21 backbone, with pharmacokinetics and CYP3A4 interaction monitoring in infants.","maturity":"early-clinical"},{"id":"idea-moon-metastasis-prevention-indication","kind":"idea","name":"Metastasis prevention as a formal indication with its own trials and regulatory pathway","aka":[],"tldr":"Metastasis causes most cancer deaths, yet no drug is developed to stop cells spreading. Create a formal approval route for drugs that prevent metastasis, tested in people at high risk of it.","summary":"Drug development targets established tumours; anti-metastatic mechanisms (blocking dissemination, colonisation or pre-metastatic niche formation) fail in trials designed to shrink measurable disease. The proposal is a recognised metastasis-prevention indication: trials in high-risk localised disease or MRD-positive patients with distant-recurrence-free survival as the endpoint, acceptance of mechanistically anti-metastatic agents without expectation of response in bulk disease, and biomarkers of dissemination (circulating tumour cells, ctDNA) as enrichment tools, developed with regulators.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Metastasis is understood least and studied last): Dillekås et al., Are 90% of deaths from cancer caused by metastases? (Cancer Medicine 2019)","url":"https://doi.org/10.1002/cam4.2474"}],"tags":[],"related":[],"cancers":["colorectal","tnbc"],"sections":[],"technologies":["mrd-testing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["neoadjuvant-adjuvant","mrd"],"trials":[],"people":[],"bottlenecks":["b-metastasis-biology","b-trial-design"],"keyPapers":["paper-dillekas-cancer-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Under the new pathway, at least two agents with anti-metastatic but not cytoreductive activity demonstrate reduced distant recurrence in randomised adjuvant trials within a decade.","rationale":"Adjuvant trials already accept recurrence endpoints; what is missing is a route for drugs whose only activity is anti-metastatic, and the biology of metastasis is now detailed enough to target.","test":"Regulatory guidance issued; first randomised MRD-enriched adjuvant trials of anti-metastatic agents in colorectal and breast cancer with distant recurrence as primary endpoint.","maturity":"speculative","actor":"regulator","cost":"large","horizonYears":8},{"id":"idea-data-thirty-day-practice-change-learning","kind":"idea","name":"Micro-learning pushed to community oncologists within 30 days of a practice change","aka":[],"tldr":"When a trial changes the standard of care, every oncologist would receive a five-minute, case-based lesson within a month, rather than waiting for the next conference.","summary":"Community oncologists treat most patients and see every cancer type; they cannot follow every subspecialty result. The proposal is a free service that, within 30 days of a practice-changing result or guideline update, delivers a short case-based module (with the plain-language summary and structured result), tracks completion, and links it to CME credit. Precedents include ASCO's education programmes and spaced-learning platforms.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Knowledge reaches practice too slowly): Morris, Wooding & Grant, The answer is 17 years, what is the question (JRSM 2011)","url":"https://doi.org/10.1258/jrsm.2011.110180"}],"tags":[],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["asco","esmo"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-knowledge-diffusion","b-workforce"],"keyPapers":["paper-morris-j-r-soc-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Oncologists receiving 30-day micro-learning will adopt new standards in their own patients measurably faster (concordance measured via structured data) than those relying on conventional channels.","rationale":"Spaced, case-based online learning has changed prescribing in trials in other specialties; the delay in oncology is partly informational and a timely push can address it.","test":"Cluster-randomise community practices to receive micro-learning for one year; measure guideline-concordant adoption of three new standards via structured data.","maturity":"speculative","actor":"clinic","cost":"small","horizonYears":2},{"id":"idea-microbiome-io-fmt","kind":"idea","name":"Microbiome transplant as a routine immunotherapy adjunct","aka":[],"tldr":"Stool transplants from immunotherapy responders have rescued some non-responders in melanoma. If defined bacterial cocktails work as well, every immunotherapy patient could get one.","summary":"This idea proposes microbiome transplant as a routine immunotherapy adjunct: stool from responders has rescued some non-responders in Melanoma, and defined bacterial cocktails could reach every immunotherapy patient. Phase 1/2 FMT studies (Davar, Baruch) converted a fraction of refractory melanoma patients, defined consortia (SER-155, VE800) and diet trials are ongoing, and durability is unclear. The hypothesis is that a defined consortium with first-line PD-1 blockade raises the response rate in melanoma and Non-small-cell lung cancer, supported by causal FMT data and the harm done by antibiotics. The test is a placebo-controlled phase 2/3, and the idea sits within the Microbiome-tumour interactions pathway and the hallmark Polymorphic microbiomes.","asOf":"2026-09-08","links":[{"label":"Davar et al., Fecal microbiota transplant overcomes resistance to anti-PD-1 therapy in melanoma (Science 2021)","url":"https://doi.org/10.1126/science.abf3363"},{"label":"Baruch et al., Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma (Science 2021)","url":"https://doi.org/10.1126/science.abb5920"}],"tags":["mechanism","open-question"],"related":[],"cancers":["melanoma","nsclc"],"sections":[],"technologies":[],"targets":["pd1"],"drugs":[],"companies":[],"institutions":["md-anderson","gustave-roussy"],"pathways":["microbiome-tumour","pd1-checkpoint"],"terms":["polymorphic-microbiomes"],"trials":["checkmate-227","checkmate-915","fianlimab-phase3-melanoma","keynote-042","relativity-098"],"people":[],"bottlenecks":[],"keyPapers":["paper-davar-science","paper-baruch-science","paper-topalian-anti-pd1-nejm-2012","paper-pd-1-nsclc-am-j-clin-oncol-2016","paper-kras-nsclc-cancer-discov-2018"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A defined bacterial consortium given with first-line PD-1 blockade increases response rate in melanoma and NSCLC compared with placebo, with effect size dependent on baseline microbiome composition.","rationale":"Consistent associations across cohorts, causal FMT data, and the fact that antibiotics worsen outcomes.","test":"Placebo-controlled phase 2/3 of a consortium plus PD-1 in first-line melanoma with stratification by baseline microbiome, endpoints ORR and PFS.","maturity":"early-clinical"},{"id":"idea-fund-first-in-class-prize","kind":"idea","name":"Milestone prizes for first-in-class mechanisms reaching human proof of concept","aka":[],"tldr":"Pay a fixed prize, of tens of millions, to the first team to show that a completely new way of attacking cancer works in patients, so that the riskiest early bets are rewarded even before a product exists.","summary":"A prize schedule for pre-specified target classes or mechanisms with no approved analogue (for example a direct MYC inhibitor, a mutant p53 reactivator with objective responses, a therapy for dormant disseminated cells, a therapy that reverses cachexia) awarded at demonstrated human proof of concept: confirmed objective responses or biomarker-validated target engagement in a phase 1/2 trial with pre-registered criteria. The prize is paid regardless of commercial path, so academic and non-profit developers qualify. It complements, rather than replaces, market rewards, which arrive too late and too uncertainly for truly novel biology.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Incentives reward me-too drugs and marginal gains): Upadhaya et al., PD1/PDL1 inhibitor clinical trial landscape (Nat Rev Drug Discov 2022)","url":"https://doi.org/10.1038/d41573-022-00030-4"}],"tags":[],"related":["idea-fund-cure-prize","idea-fund-precompetitive-undruggable-consortium"],"cancers":[],"sections":[],"technologies":[],"targets":["tp53","kras"],"drugs":[],"companies":[],"institutions":[],"pathways":["p53-cell-cycle","ras-mapk"],"terms":[],"trials":[],"people":[],"bottlenecks":["b-incentive-misalignment","b-undruggable-targets"],"keyPapers":["paper-upadhaya-nat-rev-drug-discov"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Announcing prizes of $25 to $100 million for named first-in-class milestones raises the proportion of phase 1 oncology trials testing novel mechanisms (rather than known classes) in the named areas by at least a third within five years.","rationale":"The share of oncology pipeline assets that are follow-on rather than first-in-class has grown; analyses show dozens of PD-1 antibodies and TROP2 ADCs in development. Prizes that reward the discovery step have precedent in the Breakthrough Prize and DARPA Grand Challenges, and milestone prizes reduce the risk premium that makes investors avoid novel targets.","test":"Run three prizes for three years and compare novel-mechanism trial starts in the prize areas with matched areas; also survey developers on whether the prize changed their portfolio decisions.","maturity":"speculative","actor":"philanthropy","cost":"large","horizonYears":5},{"id":"idea-fund-milestone-venture-philanthropy","kind":"idea","name":"Milestone-based venture philanthropy with royalties recycled into the pipeline","aka":[],"tldr":"Cancer charities would fund companies to hit specific development milestones, as the cystic fibrosis charity did to create Kalydeco, and take a royalty they reinvest in the next drug.","summary":"Disease foundations move from grant-giving to milestone-based development contracts with biotech and pharma: payments are released on defined preclinical and clinical milestones for an agreed indication (for example a rare sarcoma, a paediatric brain tumour, cachexia), the foundation receives royalties or equity, and returns are recycled. The Cystic Fibrosis Foundation's investment in Vertex produced ivacaftor and returned more than $3 billion through a royalty sale; the Leukemia and Lymphoma Society's Therapy Acceleration Program and the Multiple Myeloma Research Foundation have applied versions of this in blood cancers. Solid tumours and paediatric cancers have few such programmes at scale.","asOf":"2026-09-08","links":[{"label":"Cystic Fibrosis Foundation","url":"https://www.cff.org/"},{"label":"LLS Therapy Acceleration Program","url":"https://www.lls.org/therapy-acceleration-program"}],"tags":[],"related":["idea-fund-ind-enabling-fund","idea-fund-nonprofit-pharma","idea-fund-amc-paediatric-rare"],"cancers":["sarcoma","neuroblastoma","multiple-myeloma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-translational-valley","b-rare-cancers"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A consortium of cancer foundations deploying $300 million in milestone contracts over five years produces at least two registration-stage programmes in indications with no prior industry activity and a royalty stream sufficient to sustain the programme.","rationale":"Milestone contracts change what companies work on because the foundation absorbs early risk and brings patients, registries and clinical networks; blood cancer foundations attribute several approvals to this approach. Charity money used this way is leveraged several-fold by subsequent private investment.","test":"Two foundations pool a fund with a professional deal team, sign milestone contracts for five programmes, and report milestones achieved, follow-on capital raised and royalties at years three and six.","maturity":"early-clinical","actor":"philanthropy","cost":"large","horizonYears":6},{"id":"idea-prev-minimum-unit-pricing-cancer-endpoints","kind":"idea","name":"Minimum alcohol pricing evaluated with cancer endpoints","aka":[],"tldr":"Scotland's minimum price per unit cut alcohol deaths. Tracking alcohol-related cancer incidence over the next decade would show whether it also prevents cancer.","summary":"Scotland's minimum price per unit of alcohol cut alcohol-specific deaths, and this idea tracks whether it also prevents cancer by running a pre-registered long-term evaluation of alcohol-attributable cancer incidence using registry data, synthetic controls from England and modelling to guide other jurisdictions. Cancer effects lag drinking by ten to twenty years, heavy drinkers are price-sensitive and alcohol harm follows a steep deprivation gradient, so the most deprived quintile is where an effect should appear first. The test is a registry-based synthetic-control analysis updated every five years. Being tested at scale, it addresses the bottleneck Prevention we already have is not deployed and links to hepatocellular and oesophageal cancer.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Prevention we already have is not deployed): Islami et al., Proportion of cancer attributable to modifiable risk factors (CA 2018)","url":"https://doi.org/10.3322/caac.21440"}],"tags":[],"related":[],"cancers":["hcc","esophageal"],"sections":["prevention"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption"],"keyPapers":["paper-islami-ca-cancer-j-clin"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Minimum unit pricing reduces incidence of alcohol-attributable cancers (oral, oesophageal, liver, breast, colorectal) by at least 5% in the most deprived quintile within 15 years.","rationale":"Heavy drinkers are price-sensitive and alcohol harm follows a steep deprivation gradient.","test":"Registry-based synthetic-control analysis updated every five years.","maturity":"being-tested-at-scale","actor":"policy","cost":"small","horizonYears":10},{"id":"idea-acc-mobile-see-and-treat-units","kind":"idea","name":"Mobile diagnostic units that biopsy, scan and treat on the same visit","aka":[],"tldr":"Vans equipped with ultrasound, biopsy kits, cervical screening and a link to a distant pathologist could bring a cancer diagnosis, and for cervical pre-cancer immediate treatment, to villages far from any hospital.","summary":"Rural patients in LMICs often make three or four long trips before diagnosis, and patients drop out at each step. A mobile unit staffed by a nurse and a clinical officer, carrying portable ultrasound, core-biopsy equipment, HPV testing and thermal ablation, and connected to a telepathology hub, compresses the pathway into one or two visits. Mobile breast and cervical screening exists in several countries; combining diagnosis and treatment in one visit is the new step.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Most of the world has almost no cancer care): WHO fact sheet, Cancer","url":"https://www.who.int/news-room/fact-sheets/detail/cancer"}],"tags":[],"related":[],"cancers":["cervical","breast-hr-positive"],"sections":[],"technologies":["ultrasound","digital-pathology-ai"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-global-access","b-early-detection"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Communities served by a see-and-treat mobile unit will show a higher proportion of breast and cervical cancers diagnosed at stage I-II and a lower loss-to-follow-up between suspicion and diagnosis than matched communities relying on referral.","rationale":"Each additional visit before diagnosis loses a fraction of patients to cost and distance; collapsing visits is the single most effective adherence intervention in resource-limited care.","test":"Cluster-randomised evaluation across 20 rural districts with stage distribution, loss to follow-up, and cost per early-stage cancer detected as endpoints.","maturity":"early-clinical","actor":"clinic","cost":"medium","horizonYears":2},{"id":"idea-tr1-mobile-research-units","kind":"idea","name":"Mobile research units bring trial visits to rural towns","aka":[],"tldr":"A van equipped for blood draws, ECGs, questionnaires and drug hand-over could visit rural towns on a schedule so trial participants there do not have to travel hours each cycle.","summary":"Mobile units staffed by research nurses under a hub site's oversight run scheduled circuits through rural areas, performing protocol assessments, sampling and oral drug dispensing, linked by telehealth to the investigator. Mobile screening units and mobile stroke units are precedents; trial-specific units have been piloted in the US.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Trials enrol too few, too slowly): Unger et al., Systematic review of barriers to cancer trial participation (JNCI 2019)","url":"https://doi.org/10.1093/jnci/djy221"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["nci"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-enrolment","b-trial-diversity"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Regions served by mobile research units will enrol rural patients into interventional trials at a rate approaching that of urban patients, from a baseline of a small fraction.","rationale":"Rural cancer patients have worse outcomes and lower trial participation; distance is the dominant barrier. Bringing the trial to the patient removes it for most non-infusion visits.","test":"Fund two units serving a defined rural catchment and compare rural enrolment rates with matched catchments without units over two years.","maturity":"speculative","actor":"philanthropy","cost":"medium","horizonYears":3},{"id":"idea-moon-individualised-dosing-all-oral-drugs","kind":"idea","name":"Model-informed individual dosing with drug-level monitoring for every oral cancer drug","aka":[],"tldr":"People differ several-fold in how they absorb and clear cancer pills. Measure blood levels and adjust each person's dose, as is routine for some antibiotics and transplant drugs.","summary":"Exposure to oral kinase inhibitors and endocrine agents varies widely between patients and correlates with both toxicity and efficacy (imatinib, abiraterone, tamoxifen metabolites, sunitinib). Therapeutic drug monitoring is standard in other fields but rare in oncology. The proposal is a programme defining exposure targets for the top 30 oral anticancer drugs, a low-cost assay network, and model-informed precision dosing software integrated into prescribing, tested in randomised trials against fixed dosing.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Wrong doses): FDA Oncology Center of Excellence, Project Optimus","url":"https://www.fda.gov/about-fda/oncology-center-excellence/project-optimus"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["kinase-inhibitors","endocrine-therapy"],"targets":[],"drugs":["imatinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-dose-optimisation","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Exposure-guided dosing reduces grade 3+ toxicity and discontinuation by a third while maintaining or improving progression-free survival compared with fixed labelled dosing.","rationale":"Fixed dosing at the maximum tolerated dose ignores known pharmacokinetic variability; the analytic and modelling tools are mature and cheap relative to the drugs.","test":"Randomised trial of exposure-guided versus fixed dosing across five oral agents with composite toxicity-discontinuation primary and PFS non-inferiority secondary endpoints.","maturity":"early-clinical","actor":"clinic","cost":"medium","horizonYears":4},{"id":"idea-prev-modern-autopsy-reservoir-studies","kind":"idea","name":"Modern autopsy studies to measure how much silent cancer people carry","aka":[],"tldr":"Autopsy studies decades ago found hidden prostate, thyroid and breast cancers in people who died of other causes, but they pre-date modern pathology. Repeating them with whole-body imaging and standardised histology would measure the reservoir of harmless cancer that every overdiagnosis estimate depends on.","summary":"Overdiagnosis estimates depend on knowing the prevalence of indolent disease, yet the data is decades old and pre-dates modern pathology. Propose systematic autopsy series with whole-body imaging and standardised histology across ages and populations, quantifying the reservoir for prostate, thyroid, breast, kidney, lung and pancreas.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Overdiagnosis and false alarms): Welch & Black, Overdiagnosis in cancer (JNCI 2010)","url":"https://doi.org/10.1093/jnci/djq099"}],"tags":[],"related":[],"cancers":["prostate","thyroid"],"sections":["early-detection"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-overdiagnosis"],"keyPapers":["paper-welch-j-natl-cancer-inst"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Modern reservoir estimates show at least 30% prevalence of indolent cancers in adults over 60 for several organs, changing screening threshold calculations.","rationale":"MCED and imaging screening will find these lesions; we need to know how many there are before deciding what to call them.","test":"Fund 2,000 autopsies across five countries.","maturity":"speculative","actor":"research","cost":"medium","horizonYears":3},{"id":"idea-acc-modern-cobalt-bridge","kind":"idea","name":"Modernised cobalt-60 machines as a deliberate bridge where linacs cannot be kept running","aka":[],"tldr":"In places where sophisticated machines break down, a modern version of the older cobalt radiotherapy unit, upgraded with image guidance, could treat more people reliably while infrastructure catches up.","summary":"Cobalt-60 teletherapy units are mechanically simple, tolerate power instability, and need far less maintenance than linacs, but were abandoned in rich countries because of inferior beam characteristics and source-security concerns. A modernised unit with a multileaf collimator and cone-beam image guidance, with secure source logistics through the IAEA, might deliver adequate conformal treatment for common indications. This is controversial and must be tested rather than assumed.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Most of the world has almost no cancer care): WHO fact sheet, Cancer","url":"https://www.who.int/news-room/fact-sheets/detail/cancer"}],"tags":[],"related":[],"cancers":["cervical"],"sections":["radiation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-global-access","b-surgery-radiation-innovation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"For cervical, breast, and palliative indications, plans from a modernised cobalt unit will meet contemporary dose-constraint standards in at least 90% of cases, and unit uptime will exceed 95% in settings where linac uptime is under 70%.","rationale":"Appropriate technology beats the best technology if the best is switched off. The dosimetric gap between cobalt and 6 MV photons is modest for many pelvic and breast targets, and the maintenance gap is large.","test":"A planning study comparing cobalt-MLC and linac plans on 200 anonymised LMIC treatment scans against agreed constraints, followed by a two-site operational pilot measuring uptime and treatment completion.","maturity":"speculative","actor":"engineering","cost":"medium","horizonYears":4},{"id":"idea-bio1-myc-max-molecular-glue","kind":"idea","name":"Molecular glues that break the MYC-MAX partnership","aka":[],"tldr":"MYC is a cancer-driving transcription factor with no drug because it has no binding pocket. A molecular glue or degrader that jams its required partner MAX, or recruits an E3 ligase to the MYC-MAX interface, could switch it off; gluing disordered proteins now has precedent from cereblon-binding drugs.","summary":"MYC must dimerise with MAX to bind DNA. Rather than seeking an inhibitor pocket on MYC, a molecular glue or bifunctional degrader could stabilise a non-productive MYC conformation or recruit an E3 ligase to the MYC-MAX interface. Precedent for gluing intrinsically disordered proteins now exists (for example the recruitment of transcription factors to cereblon by aryl sulfonamides and CELMoD-class agents).","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The undruggable drivers): Dang et al., Drugging the 'undruggable' cancer targets (Nature Reviews Cancer 2017)","url":"https://doi.org/10.1038/nrc.2017.36"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["protac-degrader","ai-drug-design"],"targets":[],"drugs":[],"companies":["monte-rosa","c4-therapeutics","kymera"],"institutions":[],"pathways":[],"terms":["oncogene-addiction"],"trials":[],"people":[],"bottlenecks":["b-undruggable-targets"],"keyPapers":["paper-dang-nat-rev-cancer"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A compound that reduces nuclear MYC protein by 80 percent for 24 hours produces tumour regression in MYC-amplified xenografts with tolerable effects on regenerating tissues.","rationale":"Degradation avoids the need for a binding pocket, which is why glues have already drugged the previously intractable IKZF1/3 and RBM39. MYC has a short half-life, so partial degradation should have a large functional effect.","test":"Chemoproteomic glue screening against MYC-MAX in a MYC-amplified line with degradation readout, followed by tolerability studies in mouse models where MYC is required for gut and marrow renewal.","maturity":"preclinical-evidence","actor":"industry","cost":"large","horizonYears":8},{"id":"idea-moon-indolence-classifiers-with-screening","kind":"idea","name":"Molecular indolence classifiers bundled with every screening programme","aka":[],"tldr":"Screening finds cancers that would never have caused harm alongside dangerous ones. Pair every screening test with a test that says which is which, so people with harmless findings can safely watch and wait.","summary":"Overdiagnosis in prostate, thyroid, breast (DCIS) and low-dose CT lung screening leads to unnecessary surgery and anxiety and is the main argument against expanding screening. Molecular and imaging classifiers of indolence (genomic classifiers in prostate cancer, DCIS risk scores, radiomic and growth-rate models for lung nodules, ctDNA fragmentomics) are emerging but not integrated into programmes. The proposal is that every screening programme develops, validates and deploys an indolence classifier with a surveillance-first protocol for low-risk findings, and reports overdiagnosis as a monitored quality metric.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Overdiagnosis and false alarms): Welch & Black, Overdiagnosis in cancer (JNCI 2010)","url":"https://doi.org/10.1093/jnci/djq099"}],"tags":[],"related":[],"cancers":["prostate","thyroid","nsclc","breast-hr-positive"],"sections":[],"technologies":["mced","radiology-ai-screening","methylation-profiling"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["stage-shift"],"trials":[],"people":[],"bottlenecks":["b-overdiagnosis","b-early-detection","b-biomarker-validation"],"keyPapers":["paper-welch-j-natl-cancer-inst"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Classifier-guided surveillance-first protocols reduce treatment of screen-detected indolent lesions by half without increasing interval cancers or cancer-specific mortality.","rationale":"Active surveillance in low-risk prostate cancer already shows that deferring treatment is safe when risk is classified well; making classification part of the programme extends the benefit and the political viability of screening.","test":"Randomised trial within a screening programme of classifier-guided surveillance-first versus standard management for low-risk findings; primary endpoint treatment rate, secondary interval cancers and mortality at ten years.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":6},{"id":"idea-molecular-class-adjuvant-endometrial","kind":"idea","name":"Molecular-class-directed adjuvant therapy in endometrial cancer","aka":[],"tldr":"Give adjuvant treatment by the tumour's molecular class rather than by stage and grade: nothing for POLE-mutated, immunotherapy for MMRd, chemotherapy plus targeted agents for p53-abnormal, hormones for NSMP.","summary":"PORTEC-3 molecular analysis showed p53abn tumours gained the most from chemoradiation and POLEmut tumours nothing. The RAINBO programme (four parallel trials: p53abn-RED with olaparib, MMRd-GREEN with durvalumab, NSMP-ORANGE with progestin, POLEmut-BLUE de-escalation) and PORTEC-4a test this prospectively.","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT00411138: PORTEC-3","url":"https://clinicaltrials.gov/study/NCT00411138"}],"tags":[],"related":[],"cancers":["endometrial"],"sections":[],"technologies":[],"targets":["tp53"],"drugs":["durvalumab","olaparib","megestrol-progestins"],"companies":[],"institutions":[],"pathways":[],"terms":["endometrial-molecular-classes","msi"],"trials":["portec-3"],"people":[],"bottlenecks":[],"keyPapers":["paper-duo-e-jco-2023","paper-durvalumab-endometrial-j-immunother-cancer-2021","paper-durvalumab-endometrial-gynecol-oncol-2022"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Molecular-class-directed adjuvant therapy improves recurrence-free survival in p53abn and MMRd disease and safely omits adjuvant therapy in POLEmut disease compared with stage-based standard care.","rationale":"Retrospective PORTEC and TransPORTEC analyses consistently show class-specific benefit; the classifier is cheap (three IHC stains plus POLE sequencing).","test":"RAINBO and PORTEC-4a read out 2027-2030; recurrence-free survival by class.","maturity":"being-tested-at-scale"},{"id":"idea-ctdna-switch-generalised","kind":"idea","name":"Molecular-progression switching beyond ESR1","aka":[],"tldr":"SERENA-6 showed you can act on a blood test before the scan changes. The same logic could apply to PIK3CA, AKT1, or HER2 mutations emerging on treatment.","summary":"This idea generalises SERENA-6: run serial ctDNA during first-line aromatase inhibitor plus CDK4/6 therapy for HR-positive breast cancer and, when a PIK3CA or AKT1 mutation emerges, add capivasertib or inavolisib before the scan changes, with T-DXd the analogous move for HER2 activation. Resistant clones are smaller and less heterogeneous at molecular than at radiographic progression, and SERENA-6 showed that acting at this earlier point lengthens disease control. The test is a platform trial randomising at mutation emergence to an immediate pathway-matched drug versus continuation, with PFS2 as primary endpoint and patient-reported outcomes to answer the ODAC critique. At an early clinical stage, it addresses the tumour-heterogeneity and acquired-resistance bottlenecks.","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT04964934: SERENA-6","url":"https://clinicaltrials.gov/study/NCT04964934"}],"tags":[],"related":[],"cancers":["breast-hr-positive"],"sections":[],"technologies":["liquid-biopsy"],"targets":[],"drugs":["camizestrant","capivasertib","inavolisib"],"companies":[],"institutions":[],"pathways":[],"terms":["esr1-mutation","ctdna"],"trials":["serena-6"],"people":[],"bottlenecks":[],"keyPapers":["paper-capivasertib-breast-hr-positive-lancet-oncol-2022","paper-capivasertib-breast-hr-positive-breast-2022","paper-capivasertib-breast-hr-positive-drugs-2024"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"ctDNA-triggered addition of a pathway-matched agent at molecular progression improves PFS2 and time to chemotherapy versus waiting for radiographic progression.","rationale":"Resistant clones are smaller and less heterogeneous at molecular than at radiographic progression; SERENA-6 demonstrated a 7-month PFS gain with this timing.","test":"A platform trial would run serial ctDNA on first-line AI + CDK4/6 and randomise at emergence of PIK3CA/AKT1 mutation to immediate capivasertib or inavolisib vs continue; primary endpoint PFS2. Address the ODAC critique with patient-reported outcomes and OS follow-up.","maturity":"early-clinical"},{"id":"idea-tr2-positivity-rate-surveillance","kind":"idea","name":"Monitor biomarker positivity rates across labs in real time to catch assay drift","aka":[],"tldr":"If one lab suddenly reports twice the rate of 'positive' biomarker results that other labs report, its assay has probably drifted. Pooling anonymised positivity rates by laboratory, assay and version, with automated outlier detection and case-mix adjustment, would catch reagent lot problems and protocol drift within weeks rather than at occasional proficiency runs.","summary":"Statistical process control on population-level positivity rates is standard in clinical chemistry and screening programmes but not in predictive oncology biomarkers. A national feed of anonymised biomarker results by laboratory, assay and version, with automated outlier detection and case-mix adjustment, would detect reagent lot problems, protocol drift and algorithm changes within weeks rather than through occasional proficiency runs.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Biomarkers are not validated or standardised): Fernandez et al., Examination of low ERBB2 protein expression in breast cancer tissue (JAMA Oncology 2022)","url":"https://doi.org/10.1001/jamaoncol.2021.7239"}],"tags":[],"related":["idea-tr2-eqa-public-results","idea-tr2-ai-cdx-change-control"],"cancers":[],"sections":[],"technologies":["histopathology-ihc"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-biomarker-validation","b-data-silos"],"keyPapers":["paper-fernandez-jama-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Surveillance will identify at least two laboratory-level drift events per year in a national system, each confirmed on re-testing, that proficiency schemes had not detected.","rationale":"Screening programmes detect reader drift through recall-rate monitoring; the same logic applies to any test with a stable expected positivity rate.","test":"Pilot with PD-L1 and HER2 results from 30 laboratories over one year; investigate flagged outliers with sample re-testing.","maturity":"speculative","actor":"data","cost":"small","horizonYears":2},{"id":"idea-mrd-guided-transplant-aml","kind":"idea","name":"MRD-guided transplant decisions in intermediate-risk AML","aka":[],"tldr":"Use ultra-sensitive residual-disease tests after induction to decide who really needs a transplant, sparing the rest its risks.","summary":"The idea is to use ultra-sensitive residual disease tests, NPM1 qPCR or error-corrected NGS, after two cycles of induction to decide which intermediate-risk acute myeloid leukaemia patients really need an allogeneic transplant. MRD status is the strongest predictor of relapse, transplant carries substantial risk, and its benefit concentrates in MRD-positive patients; ELN 2022 already recommends transplant for them, but randomised confirmation is lacking. The hypothesis is that MRD-negative patients can receive chemotherapy consolidation instead with equal overall survival and less toxicity. The test randomises MRD-negative patients to transplant or consolidation with MRD surveillance; myeloMATCH, HOVON and AMLSG trials already stratify by MRD, so it is being tested at scale.","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT05564390: myeloMATCH","url":"https://clinicaltrials.gov/study/NCT05564390"}],"tags":[],"related":[],"cancers":["aml"],"sections":[],"technologies":["ngs-mrd-clonoseq","allogeneic-hsct"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["mrd-negative-cr","eln-risk"],"trials":["myelomatch"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Intermediate-risk AML patients who are MRD-negative by NPM1 qPCR or error-corrected NGS after two cycles can safely receive chemotherapy consolidation instead of allogeneic transplant, with equal OS and less toxicity.","rationale":"MRD status is the strongest predictor of relapse; transplant carries 10-20% mortality; retrospective data show transplant benefit concentrates in MRD-positive patients.","test":"Randomised MRD-negative intermediate-risk patients to transplant vs consolidation with MRD surveillance and pre-emptive therapy at molecular relapse; primary endpoint OS.","maturity":"being-tested-at-scale"},{"id":"idea-mrd-guided-stop-cll","kind":"idea","name":"MRD-guided treatment duration in CLL","aka":[],"tldr":"Instead of a fixed 12 or 15 months, stop each patient's therapy when their blood shows no detectable leukaemia, and restart if it returns.","summary":"The idea is to stop each chronic lymphocytic leukaemia patient's fixed-duration therapy when an NGS-based MRD assay such as clonoSEQ shows no detectable leukaemia in blood, and to restart at relapse, rather than treating everyone for a fixed twelve or fifteen months. Undetectable MRD at the end of treatment is the strongest predictor of progression-free survival, and patients with mutated IGHV reach it earlier and stay in remission longer. The hypothesis is non-inferior progression-free survival with a third less drug exposure. CAPTIVATE's MRD-guided cohort and FLAIR's MRD-directed arm suggest this is feasible, SPRUCE-TN with sonrotoclax and zanubrutinib formalises it, and retreatment at relapse works in most patients; the idea is being tested at scale.","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT02910583: CAPTIVATE","url":"https://clinicaltrials.gov/study/NCT02910583"},{"label":"ClinicalTrials.gov NCT06073821: CELESTIAL-TNCLL","url":"https://clinicaltrials.gov/study/NCT06073821"}],"tags":[],"related":[],"cancers":["cll"],"sections":[],"technologies":["ngs-mrd-clonoseq"],"targets":[],"drugs":["venetoclax","zanubrutinib","sonrotoclax"],"companies":[],"institutions":[],"pathways":[],"terms":["mrd-negative-cr","ighv-status"],"trials":["captivate","celestial-tncll"],"people":[],"bottlenecks":[],"keyPapers":["paper-zanubrutinib-cll-n-engl-j-med-2023","paper-zanubrutinib-cll-lancet-oncol-2022","paper-zanubrutinib-cll-lancet-haematol-2021"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"MRD-guided duration (stop at confirmed uMRD ≤10^-4, or continue to a maximum) yields PFS non-inferior to fixed 12-15 months while reducing drug exposure by a third.","rationale":"uMRD at end of treatment is the strongest predictor of PFS; IGHV-mutated patients reach uMRD earlier and stay in remission longer.","test":"Randomised MRD-guided vs fixed duration with clonoSEQ monitoring every 3 months; primary endpoint PFS, secondary exposure and cost.","maturity":"being-tested-at-scale"},{"id":"idea-mrd-guided-stop-myeloma","kind":"idea","name":"MRD-guided treatment-free intervals in myeloma","aka":[],"tldr":"If a patient has had no detectable myeloma for a year or more, stop maintenance and watch, restarting only if disease reappears.","summary":"For a patient with multiple myeloma whose disease has been undetectable by MRD testing for a year or more, this idea proposes stopping maintenance and watching, restarting only if disease reappears. The rationale is that sustained MRD negativity at the most sensitive threshold predicts a very low rate of relapse, that MRD re-emergence precedes clinical relapse by months, and that indefinite lenalidomide adds toxicity, second cancers and cost. The hypothesis is that stopping after twelve months of sustained MRD negativity gives non-inferior progression-free survival with better quality of life. PERSEUS, MASTER, DRAMMATIC (SWOG S1803) and GEM2014MAIN test stopping, so it is being tested at scale; it addresses the bottlenecks of dormant cells and minimal residual disease and of trial design.","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT03710603: PERSEUS","url":"https://clinicaltrials.gov/study/NCT03710603"}],"tags":[],"related":[],"cancers":["multiple-myeloma"],"sections":[],"technologies":["mrd-testing"],"targets":[],"drugs":["lenalidomide","daratumumab"],"companies":[],"institutions":[],"pathways":[],"terms":["mrd-negativity-myeloma"],"trials":["perseus"],"people":[],"bottlenecks":[],"keyPapers":["paper-lenalidomide-multiple-myeloma-n-engl-j-med-2016","paper-lenalidomide-multiple-myeloma-n-engl-j-med-2007","paper-lenalidomide-multiple-myeloma-n-engl-j-med-2015"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Stopping maintenance after ≥12 months sustained MRD negativity (10⁻⁶) yields non-inferior PFS at 3 years compared with continued lenalidomide, with better quality of life.","rationale":"MRD-negative CR at 10⁻⁶ carries ~90% 5-year PFS in modern cohorts; MRD re-emergence precedes clinical relapse by months, allowing pre-emptive restart.","test":"Randomised MRD-guided discontinuation with serial marrow/peripheral MRD and PET; PFS non-inferiority primary.","maturity":"being-tested-at-scale"},{"id":"idea-mri-surveillance-replaces-pci","kind":"idea","name":"MRI surveillance replaces prophylactic cranial irradiation in SCLC","aka":[],"tldr":"Instead of irradiating every patient's brain to prevent metastases, scan regularly and treat the few who develop them with focused radiation.","summary":"Rather than giving prophylactic cranial irradiation to every patient with small-cell lung cancer, this idea proposes MRI surveillance every three months with stereotactic radiosurgery reserved for the few who develop brain metastases. The rationale is that the benefit of PCI was shown before brain MRI was routine, and many patients irradiated would never have developed brain disease. The hypothesis is that surveillance with salvage SRS is non-inferior to PCI for overall survival and superior for cognition. A Japanese extensive-stage trial supports the approach, and the randomised SWOG S1827 MAVERICK trial of PCI versus MRI surveillance is the definitive test. Being tested at scale, it bears on the bottleneck of the brain as barrier and sanctuary.","asOf":"2026-09-07","links":[{"label":"Takahashi et al., Prophylactic cranial irradiation versus MRI observation in extensive-stage small-cell lung cancer (Lancet Oncology 2017)","url":"https://doi.org/10.1016/S1470-2045(17)30230-9"}],"tags":[],"related":[],"cancers":["sclc"],"sections":[],"technologies":["prophylactic-cranial-irradiation","mri","sbrt"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-takahashi-lancet-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"MRI surveillance every 3 months with salvage SRS is non-inferior to PCI for overall survival and superior for cognition.","rationale":"PCI's benefit was shown before routine brain MRI; many patients irradiated never develop brain disease.","test":"SWOG S1827 (MAVERICK), randomised PCI vs MRI surveillance, OS primary endpoint.","maturity":"being-tested-at-scale"},{"id":"idea-prev-mri-first-prostate-screening-prs","kind":"idea","name":"MRI-first prostate screening with genetic pre-selection","aka":[],"tldr":"PSA screening finds harmless prostate cancers that would never cause trouble. Selecting men by PSA plus a polygenic risk score, then MRI before any biopsy and targeted biopsy only for PI-RADS 4 to 5 lesions, finds the dangerous cancers and skips the rest; GOTEBORG-2 showed MRI-targeted biopsy halves overdiagnosis.","summary":"GOTEBORG-2 showed MRI-targeted biopsy halves overdiagnosis; BARCODE1 showed polygenic-score-selected men have high rates of clinically significant cancer. The UK TRANSFORM trial will compare pathways. Propose a national screening design combining PRS/PSA pre-selection, MRI, and targeted biopsy only for PI-RADS 4-5 lesions.","asOf":"2026-09-08","links":[{"label":"Prostate Cancer UK (TRANSFORM)","url":"https://prostatecanceruk.org"}],"tags":[],"related":["prostate-roadmap","idea-prostate-metastatic-presentation-as-the-screening-endpoint","idea-prostate-per-lesion-mri-audit-before-focal-treatment"],"cancers":["prostate"],"sections":["early-detection","imaging"],"technologies":["mri","germline-testing"],"targets":[],"drugs":[],"companies":[],"institutions":["icr-london"],"pathways":[],"terms":["polygenic-risk-score","pi-rads"],"trials":[],"people":[],"bottlenecks":["b-early-detection","b-overdiagnosis"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"The combined pathway detects clinically significant (Gleason 7 and above) cancer at rates similar to PSA screening while cutting Gleason 6 detection by at least half and biopsies by at least 40%.","rationale":"Each component has randomised support; the combination is the programme design step.","test":"Embedded arm in TRANSFORM or a national pilot.","maturity":"being-tested-at-scale","actor":"policy","cost":"large","horizonYears":6},{"id":"idea-bio1-omomyc-mrna","kind":"idea","name":"mRNA-delivered MYC decoy proteins instead of MYC inhibitors","aka":[],"tldr":"A decoy protein can bind MYC's partner and block it. Delivering the instructions for that decoy as mRNA in a fat nanoparticle avoids having to inject the protein itself.","summary":"Omomyc, a dominant-negative MYC variant, shrinks tumours in mouse models and a purified-protein version (OMO-103) has completed a first-in-human study with signs of target engagement. Protein delivery is the limitation. Encoding Omomyc-like miniproteins in lipid-nanoparticle mRNA, as used for COVID vaccines and now for intratumoural cytokines, would allow repeated dosing and tumour-biased delivery.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The undruggable drivers): Dang et al., Drugging the 'undruggable' cancer targets (Nature Reviews Cancer 2017)","url":"https://doi.org/10.1038/nrc.2017.36"}],"tags":[],"related":[],"cancers":["sclc","pancreatic"],"sections":[],"technologies":["neoantigen-mrna-vaccine"],"targets":[],"drugs":[],"companies":["moderna","orna-therapeutics"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-undruggable-targets"],"keyPapers":["paper-dang-nat-rev-cancer"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"LNP-mRNA expression of a MYC decoy achieves sustained nuclear expression in tumour tissue and produces at least equivalent tumour growth inhibition to purified Omomyc protein at a lower dose.","rationale":"mRNA delivery has solved manufacturing and repeat-dosing problems for other hard-to-deliver proteins; the decoy mechanism is genetically validated across many MYC-driven models.","test":"Head-to-head mouse study of LNP-mRNA decoy versus protein in MYC-driven lung and pancreatic models, with tumour and liver biodistribution and marrow toxicity as co-primary readouts.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":6},{"id":"idea-tr1-mams-for-sequencing-questions","kind":"idea","name":"Multi-arm, multi-stage trials to answer which order to give approved drugs","aka":[],"tldr":"Several drugs are approved for the same cancer, but nobody tests which order works best because no company benefits from the answer. Public multi-arm trials could settle these questions efficiently.","summary":"Cooperative groups run multi-arm multi-stage (MAMS) trials comparing sequences of already-approved agents (e.g., ADC then checkpoint inhibitor versus the reverse; endocrine-CDK4/6 sequencing; TKI order in RCC), with interim futility dropping of arms and OS or TTF across the sequence as the primary endpoint. Drug supply comes from companies under a neutral-access agreement; funding from payers and public agencies who bear the cost of wrong sequences.","asOf":"2026-09-08","links":[{"label":"STAMPEDE trial","url":"https://www.stampedetrial.org/"}],"tags":[],"related":[],"cancers":["rcc","breast-hr-positive","urothelial"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["adc-sequencing","basket-umbrella-platform"],"trials":[],"people":[],"bottlenecks":["b-trial-design","b-incentive-misalignment"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Sequencing MAMS trials will identify orderings that improve OS or reduce cost by a clinically meaningful margin in at least half of the indications tested.","rationale":"Sequencing decisions currently rest on cross-trial inference and marketing. STAMPEDE showed MAMS can answer several questions in one structure; payers have a direct incentive to fund it.","test":"Launch one sequencing MAMS in a cancer with three or more approved second-line options and report the first interim arm decisions within three years.","maturity":"early-clinical","actor":"research","cost":"large","horizonYears":5},{"id":"idea-prev-mced-non-specific-symptom-triage","kind":"idea","name":"Multi-cancer blood test as the first step for patients with non-specific symptoms","aka":[],"tldr":"People with vague symptoms such as fatigue and weight loss are worked up with repeated scans. A multi-cancer blood test as the first step in Rapid Diagnostic Centres could point to which organ to examine first, or safely reassure; SYMPLIFY showed the Galleri test has high specificity in symptomatic patients.","summary":"People with vague symptoms such as fatigue and weight loss undergo repeated scans, so this idea makes a multi-cancer blood test the first step in Rapid Diagnostic Centre pathways, pointing to which organ to examine first or safely reassuring. SYMPLIFY from Oxford showed that Galleri, the GRAIL MCED, had high specificity and useful tissue-of-origin accuracy in symptomatic patients, and because cancer prevalence in symptomatic referrals is far higher than in screening, positive predictive value is better. An RCT would compare MCED-directed with standard work-up on time to diagnosis, imaging use and stage. The test is a 6,000-patient trial across ten NHS Rapid Diagnostic Centres. At early-clinical maturity it addresses the bottleneck The hardest cancers are found late.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The hardest cancers are found late): Crosby et al., Early detection of cancer (Science 2022)","url":"https://doi.org/10.1126/science.aay9040"}],"tags":[],"related":[],"cancers":[],"sections":["early-detection","diagnostics"],"technologies":["mced"],"targets":[],"drugs":["galleri"],"companies":["grail"],"institutions":[],"pathways":[],"terms":["ppv"],"trials":[],"people":[],"bottlenecks":["b-early-detection"],"keyPapers":["paper-crosby-science"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"MCED-first triage shortens median time to diagnosis by at least seven days and cuts imaging procedures per cancer diagnosed by at least 25% without missing cancers.","rationale":"Cancer prevalence in symptomatic referrals (about 7%) is ten times that of screening, so positive predictive value is far better and overdiagnosis less of a concern.","test":"Run a 6,000-patient RCT across ten NHS Rapid Diagnostic Centres.","maturity":"early-clinical","actor":"clinic","cost":"medium","horizonYears":3},{"id":"idea-bio1-multicentre-mouse-trials","kind":"idea","name":"Multi-centre randomised animal trials before committing to a human trial","aka":[],"tldr":"A drug that works in one laboratory's mice often fails elsewhere. Running the confirmatory animal study as a randomised, blinded, multi-laboratory trial, as stroke and amyotrophic lateral sclerosis research has done, would catch this before a human trial; oncology has no such standing infrastructure.","summary":"The confirmatory preclinical trial concept borrows randomisation, blinding, power calculation and multi-site replication from clinical research. Multi-laboratory preclinical trials have been run in stroke (the MULTI-PART approach) and in amyotrophic lateral sclerosis, and reversed several accepted findings. Oncology, where phase 2 attrition is highest, has no equivalent standing infrastructure.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Lab models that fail to predict what happens in patients): Wong, Siah & Lo, Estimation of clinical trial success rates (Biostatistics 2019)","url":"https://doi.org/10.1093/biostatistics/kxx069"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["pdx-models"],"targets":[],"drugs":[],"companies":[],"institutions":["nci","cruk"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-preclinical-models","b-reproducibility","b-translational-valley"],"keyPapers":["paper-wong-biostatistics"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Candidates that pass a randomised, blinded, three-laboratory confirmatory preclinical trial have a materially higher phase 2 success rate than candidates advanced on single-laboratory data.","rationale":"The main source of translational failure is unreliable effect estimates rather than species differences alone; replication is the cheapest available fix and costs a fraction of a failed phase 2.","test":"Fund a preclinical trials network to run confirmatory studies for ten agents heading into phase 2 and track subsequent clinical outcomes against matched controls.","maturity":"preclinical-evidence","actor":"philanthropy","cost":"medium","horizonYears":6},{"id":"idea-tr2-multilab-preclinical","kind":"idea","name":"Multi-laboratory preclinical trials as the standard for go/no-go decisions","aka":[],"tldr":"Instead of one lab's mouse study deciding whether a drug goes to patients, several labs run the same protocol independently, like a multi-centre clinical trial for mice.","summary":"Multi-centre preclinical randomised trials (for example the Multi-PART stroke consortium and EQIPD in Europe) show that effect sizes shrink and heterogeneity appears when protocols are run across sites, exposing fragile findings before they reach patients. In oncology, a standing network of laboratories that runs pre-registered, blinded, multi-site efficacy studies for compounds approaching translation would replace single-lab evidence with robust estimates.","asOf":"2026-09-08","links":[{"label":"EQIPD","url":"https://eqipd.org/"}],"tags":[],"related":["idea-tr2-replication-before-ind","champions-oncology"],"cancers":[],"sections":[],"technologies":["pdx-models"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-reproducibility","b-preclinical-models"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Effect sizes from multi-lab studies will predict early clinical activity better than the originating lab's results, and at least a third of compounds will show effects too small or inconsistent across sites to justify clinical testing.","rationale":"Heterogeneity between sites is a feature: findings that survive it are the ones likely to survive human heterogeneity.","test":"Run ten compounds through a five-lab network with pre-registered protocols; compare effect sizes with the original publications and with subsequent clinical outcomes.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":3},{"id":"idea-acc-prehabilitation-older-surgery","kind":"idea","name":"Multimodal prehabilitation for older patients before major cancer surgery","aka":[],"tldr":"A few weeks of exercise, nutrition and mental preparation before a big operation helps older patients recover faster and with fewer complications. It costs little and should be routine.","summary":"Prehabilitation programmes combining exercise, nutritional optimisation, and psychological support before surgery have shown reductions in complications and length of stay in colorectal and other cancer surgery, including in randomised trials, with the largest effects in frail and older patients. The waiting time before surgery is usually long enough. Making prehabilitation a standard offer for patients over 70 scheduled for major cancer surgery would apply existing evidence.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Older and multimorbid patients are excluded and undertreated): Mohile et al., Evaluation of geriatric assessment and management on toxic effects of cancer treatment (GAP70+, Lancet 2021)","url":"https://doi.org/10.1016/S0140-6736(21)01789-X"}],"tags":[],"related":["idea-exercise-as-adjuvant"],"cancers":["colorectal","gastric"],"sections":["surgery","rejuvenation"],"technologies":["exercise-oncology"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-aging-comorbidity","b-surgery-radiation-innovation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Prehabilitation will reduce postoperative complications by at least 25% and length of stay by at least one day in patients over 70, with improved functional recovery at three months.","rationale":"Physiological reserve determines surgical outcome in older patients and is modifiable in weeks; the evidence base is now sufficient for implementation.","test":"A stepped-wedge implementation across ten surgical units with complications, length of stay, and functional recovery as endpoints.","maturity":"being-tested-at-scale","actor":"clinic","cost":"small","horizonYears":2},{"id":"idea-tr1-mutual-recognition-ethics-review","kind":"idea","name":"Mutual recognition of ethics review across countries","aka":[],"tldr":"A trial approved by a qualified ethics committee in one country would not need to repeat the full review in another; the second country would accept the first review and check only local issues.","summary":"Building on the EU Clinical Trials Regulation single-assessment model and the US single-IRB requirement, a treaty or regulatory reliance agreement would allow ethics committees in participating countries (EU, UK, Switzerland, Canada, Australia, Japan) to rely on a lead committee's scientific and ethical assessment, with local review limited to consent language, insurance and site suitability.","asOf":"2026-09-08","links":[{"label":"EU Clinical Trials Information System","url":"https://euclinicaltrials.eu/"},{"label":"NCI Central IRB","url":"https://www.ncicirb.org/"}],"tags":[],"related":["eudract-ctis"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["curie-nki-eortc"],"institutions":["esmo"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-enrolment","b-regulatory-fragmentation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Multinational oncology trials in participating countries will start enrolment 2-4 months earlier in second and later countries, and more small countries will be included in pivotal trials.","rationale":"Regulatory reliance already works for drug approvals (Access Consortium, Project Orbis). Duplicate ethics review rarely changes a protocol but routinely delays it.","test":"Pilot reliance between two willing jurisdictions for cooperative-group trials; measure time from lead approval to first patient in the second country compared with matched historical trials.","maturity":"speculative","actor":"regulator","cost":"small","horizonYears":4},{"id":"idea-reg-mutual-recognition-inspections-atmp","kind":"idea","name":"Mutual recognition of GMP inspections for cell, gene and radiopharmaceutical plants","aka":[],"tldr":"Factories making living or radioactive cancer medicines are inspected separately by each country. Accepting each other's inspections would free up inspectors and speed supply.","summary":"The EU-US Mutual Recognition Agreement covers inspections of most human medicines but has been slow to extend to advanced therapy medicinal products and has no equivalent with Japan, China or India for these classes. Cell-therapy and radiopharmaceutical sites face repeated inspections by multiple agencies, each a multi-week interruption. The proposal is to extend PIC/S and MRA reliance explicitly to ATMP and radiopharmaceutical manufacturing, with a shared inspection schedule and a common inspection report template.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Regulatory divergence between regions): FDA Oncology Center of Excellence, Project Orbis","url":"https://www.fda.gov/about-fda/oncology-center-excellence/project-orbis"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["car-t","radioligand-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-regulatory-fragmentation","b-manufacturing-cell-therapy"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Extending mutual recognition reduces the number of inspections per ATMP site per year by at least half and shortens the time from site readiness to multi-region supply by six months or more, with no increase in critical GMP findings.","rationale":"GMP standards for ATMPs are already largely harmonised through PIC/S Annex 2A. Duplicate inspections find the same things; the cost is capacity that could inspect new sites instead.","test":"Pilot mutual recognition for ten ATMP and radiopharmaceutical sites between FDA, EMA and MHRA, tracking inspection counts, findings and time-to-supply against matched non-participating sites.","maturity":"early-clinical","actor":"regulator","cost":"small","horizonYears":3},{"id":"idea-acc-hub-spoke-national-networks","kind":"idea","name":"National hub-and-spoke cancer networks with defined referral tiers","aka":[],"tldr":"Instead of one overwhelmed national cancer hospital, organise care in tiers: district hospitals diagnose and give simple treatment, regional centres give chemotherapy and surgery, and the hub handles radiotherapy and complex cases.","summary":"Low- and middle-income countries often have a single national cancer institute that patients travel days to reach, with everything else undefined. Formal networks with tiered service specifications, referral criteria, shared protocols, and a common minimum dataset (the Tata Memorial National Cancer Grid in India is the largest example) spread capacity, shorten travel, and make quality auditable. The design choices are which services sit at which tier and how the money follows the patient.","asOf":"2026-09-08","links":[{"label":"Tata Memorial Centre","url":"https://tmc.gov.in/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["tata-memorial"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-global-access","b-care-fragmentation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Regions organised into a formal tiered network will reduce median distance travelled for chemotherapy by more than half and increase the proportion of patients completing planned curative treatment by at least 15 percentage points within five years.","rationale":"The National Cancer Grid grew to more than 300 centres and demonstrates protocol harmonisation and pooled procurement at scale; stroke and trauma networks show the same logic in other conditions.","test":"Compare two regions in one country, one with a funded network and one without, on stage at diagnosis, time to treatment, completion rates, and travel burden over three years.","maturity":"being-tested-at-scale","actor":"policy","cost":"large","horizonYears":5},{"id":"idea-acc-balanced-opioid-policy-reform","kind":"idea","name":"National opioid quota reform so morphine reaches cancer patients","aka":[],"tldr":"Most of the world's people who die in cancer pain have no access to morphine, a drug that costs pennies, because of restrictive national rules. Fixing the rules, not inventing new drugs, is the answer.","summary":"The Lancet Commission on Global Access to Palliative Care and Pain Relief estimated that the great majority of the world's need for opioid analgesia in serious illness goes unmet, concentrated in low- and middle-income countries. Barriers are regulatory: unrealistic national import estimates submitted to the International Narcotics Control Board, prescribing restricted to a few specialists, short prescription limits, and fear of prosecution. A country-level reform package with realistic quota estimation, expanded prescriber lists, and prescribing training could change this in years.","asOf":"2026-09-08","links":[{"label":"Lancet Commission on palliative care and pain relief","url":"https://www.thelancet.com/commissions/palliative-care"},{"label":"International Narcotics Control Board","url":"https://www.incb.org/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-palliative","b-global-access"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Countries adopting the reform package will at least triple per-capita medical morphine consumption within three years, with no measurable rise in diversion indicators.","rationale":"Uganda, Kerala, and several Latin American countries expanded access dramatically through regulatory change alone; the drug is on every essential medicines list.","test":"Technical assistance to five countries with INCB consumption statistics, prescriber numbers, and hospital pain-audit results tracked against matched non-participating countries.","maturity":"being-tested-at-scale","actor":"policy","cost":"small","horizonYears":3},{"id":"idea-neoadjuvant-adc-io","kind":"idea","name":"Neoadjuvant ADC + IO replacing anthracycline chemotherapy in TNBC","aka":[],"tldr":"Replace the toughest part of pre-surgery chemotherapy with an ADC plus immunotherapy, aiming for the same cure rate with less harm.","summary":"This idea replaces the anthracycline part of pre-surgery chemotherapy in TNBC with a TROP2 ADC plus pembrolizumab, aiming for the same cure rate with less harm. The KEYNOTE-522 backbone carries cardiac and leukaemia risk from anthracyclines, while ADCs deliver the same chemotherapy class more selectively and ADC-induced immunogenic death complements checkpoint blockade. Sacituzumab govitecan and datopotamab deruxtecan with pembrolizumab already show activity in metastatic disease and in the NeoSTAR and I-SPY 2 arms. The test is a randomised phase 3 against the KEYNOTE-522 regimen with pathologic complete response and then event-free survival endpoints. At early-clinical maturity it bears on the ADC plus checkpoint inhibitor pairing and the SCARLET trial.","asOf":"2026-09-04","links":[{"label":"ClinicalTrials.gov NCT03036488: KEYNOTE-522","url":"https://clinicaltrials.gov/study/NCT03036488"},{"label":"ClinicalTrials.gov NCT05929768: SCARLET (SWOG S2212)","url":"https://clinicaltrials.gov/study/NCT05929768"}],"tags":[],"related":["adc-plus-io"],"cancers":["tnbc"],"sections":[],"technologies":["adc","checkpoint-inhibitor"],"targets":[],"drugs":["sacituzumab-govitecan","datopotamab-deruxtecan","pembrolizumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["keynote-522","scarlet-s2212"],"people":[],"bottlenecks":[],"keyPapers":["paper-keynote-522-n-engl-j-med-2020","paper-keynote-355-lancet-2020","paper-ascent-nejm-2021"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Neoadjuvant TROP2 ADC + pembrolizumab achieves non-inferior pCR and EFS to KEYNOTE-522 with fewer grade 3+ toxicities.","rationale":"ADC payloads are the same chemotherapy class delivered more selectively; ADC-induced immunogenic death complements pembrolizumab.","test":"Randomised phase 3 versus KEYNOTE-522 regimen with pCR then EFS endpoints; TIL-high and HER2-low subgroups pre-specified.","maturity":"early-clinical"},{"id":"idea-neoadjuvant-io-glioblastoma","kind":"idea","name":"Neoadjuvant immunotherapy with surgical window for glioblastoma","aka":[],"tldr":"Give immunotherapy before surgery rather than after, so the tumour is still present to teach the immune system, then look inside it to learn what happened.","summary":"A Nature Medicine 2019 study by Cloughesy and colleagues showed that neoadjuvant pembrolizumab in recurrent glioblastoma increased interferon signatures and T-cell clonal expansion and was associated with longer OS than adjuvant-only in a small randomised study, the only positive checkpoint signal in the disease. Window-of-opportunity designs (GESTALT, ASCO 2026) show feasibility.","asOf":"2026-09-06","links":[{"label":"ClinicalTrials.gov NCT02667587: CheckMate 548","url":"https://clinicaltrials.gov/study/NCT02667587"},{"label":"ClinicalTrials.gov NCT02017717: CheckMate 143","url":"https://clinicaltrials.gov/study/NCT02017717"},{"label":"ClinicalTrials.gov NCT02617589: CheckMate 498","url":"https://clinicaltrials.gov/study/NCT02617589"}],"tags":[],"related":[],"cancers":["glioblastoma"],"sections":[],"technologies":["checkpoint-inhibitor","glioma-car-t"],"targets":[],"drugs":["pembrolizumab","nivolumab"],"companies":[],"institutions":[],"pathways":[],"terms":["neoadjuvant-adjuvant","cold-vs-hot"],"trials":["checkmate-143","checkmate-498","checkmate-548"],"people":[],"bottlenecks":[],"keyPapers":["paper-pembrolizumab-glioblastoma-clin-cancer-res-2021","paper-pembrolizumab-glioblastoma-med-2025","paper-pembrolizumab-glioblastoma-clin-cancer-res-2025"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Neoadjuvant PD-1 blockade ± vaccine or CAR-T, with steroid minimisation, improves OS in recurrent glioblastoma compared with adjuvant-only administration.","rationale":"Antigen supply from intact tumour, tissue-based pharmacodynamic read-outs, and avoidance of post-operative lymphopenia and dexamethasone.","test":"Randomised phase 2 neoadjuvant-plus-adjuvant versus adjuvant-only PD-1 in resectable recurrent GBM with mandated steroid protocols; OS primary, tissue immune correlates secondary.","maturity":"early-clinical"},{"id":"idea-prev-new-onset-diabetes-pancreas-pathway","kind":"idea","name":"New diabetes after 50 plus weight loss triggers a pancreatic cancer check","aka":[],"tldr":"About one in a hundred people who develop diabetes after 50, more if they are losing weight, have pancreatic cancer. A simple score could send them for a scan or blood test.","summary":"New diabetes after 50, especially with weight loss, can be an early sign of pancreatic cancer, so this idea builds an automated EHR alert around the Mayo Clinic ENDPAC score, which uses age, weight change and glucose trajectory, and sends high-scoring patients for CT or MRI or a CA19-9 or methylation blood test. New-onset diabetes is a paraneoplastic effect of early pancreatic cancer, the window is one to three years, and the population can be enumerated in primary care. The aim is to raise the share of pancreatic cancers among new diabetics diagnosed at a resectable stage. A cluster-randomised trial across primary care networks would measure stage at diagnosis, resection rate and scans per cancer. At early-clinical maturity, it addresses the bottleneck The hardest cancers are found late.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The hardest cancers are found late): Crosby et al., Early detection of cancer (Science 2022)","url":"https://doi.org/10.1126/science.aay9040"}],"tags":[],"related":[],"cancers":["pancreatic"],"sections":["early-detection"],"technologies":["ct","mri","liquid-biopsy"],"targets":[],"drugs":[],"companies":[],"institutions":["mayo-clinic"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-early-detection"],"keyPapers":["paper-crosby-science"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"ENDPAC-triggered work-up raises the proportion of pancreatic cancers diagnosed at resectable stage among new-onset diabetics from about 15% to at least 35%.","rationale":"New diabetes is a paraneoplastic effect of early pancreatic cancer; the window is one to three years and the population is enumerable in primary care.","test":"Cluster-randomised trial across primary care networks; endpoints stage at diagnosis, resection rate, and scans per cancer.","maturity":"early-clinical","actor":"clinic","cost":"medium","horizonYears":4},{"id":"idea-tr2-contribution-of-components-mandate","kind":"idea","name":"No accelerated approval for a combination without proof each part contributes","aka":[],"tldr":"Regulators should refuse to approve a two-drug combination unless there is evidence that both drugs are doing something, so patients are not exposed to useless extra toxicity and cost.","summary":"Several combinations (for example anti-TIGIT plus PD-L1, IDO inhibitor plus PD-1) reached phase 3 without randomised evidence of the added agent's contribution and failed. FDA guidance on co-development already asks for contribution-of-components data but allows exceptions. Making a randomised contribution assessment (or a factorial design) a firm condition of accelerated approval for combinations would redirect development effort towards combinations with evidence of synergy.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Too many combinations to test): Palmer & Sorger, Combination cancer therapy can confer benefit via patient-to-patient variability without drug additivity or synergy (Cell 2017)","url":"https://doi.org/10.1016/j.cell.2017.11.009"}],"tags":[],"related":["tigit-plus-pd1-caution"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":["tiragolumab","epacadostat"],"companies":[],"institutions":[],"pathways":[],"terms":["accelerated-approval"],"trials":["impassion131"],"people":[],"bottlenecks":["b-combination-space","b-incentive-misalignment"],"keyPapers":["paper-palmer-cell"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Combination phase 3 failure rates fall by at least a third within five years of a firm contribution-of-components requirement, as measured against the preceding five years.","rationale":"The TIGIT and IDO programmes together consumed thousands of patients and billions of dollars with single-arm or non-randomised phase 2 evidence. Randomised phase 2 with a contribution arm would have flagged the lack of effect.","test":"Audit the last decade of combination phase 3 failures for whether a contribution-of-components study existed; model the effect of a requirement; implement via guidance and track.","maturity":"early-clinical","actor":"regulator","cost":"small","horizonYears":2},{"id":"idea-tr2-radiomics-ibsi-mandate","kind":"idea","name":"No clinical claims for imaging-derived biomarkers without phantom and standards compliance","aka":[],"tldr":"Thousands of papers extract 'radiomic' features from scans to predict outcomes, but the features change with scanner settings. Journals should require standard compliance before any clinical claim is made.","summary":"Radiomic features vary with acquisition, reconstruction and software; the Image Biomarker Standardisation Initiative (IBSI) defined reference values and benchmark datasets, but most published radiomics studies do not report compliance or test-retest reproducibility. Journals and funders requiring IBSI compliance, phantom-based feature stability testing and external validation for any radiomic biomarker claiming clinical relevance would cut the noise.","asOf":"2026-09-08","links":[{"label":"Image Biomarker Standardisation Initiative","url":"https://theibsi.github.io/"}],"tags":[],"related":["lunit","aidoc"],"cancers":[],"sections":[],"technologies":["ct","mri","pet-ct"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-biomarker-validation","b-ai-validation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Adopting the requirement will reduce the number of published radiomic signatures by more than half and increase the fraction that replicate in external cohorts from a small minority to a majority.","rationale":"The field's replication crisis is well documented in systematic reviews; the standards exist and are unenforced.","test":"Two radiology journals adopt the requirement; compare external validation rates of signatures published before and after.","maturity":"early-clinical","actor":"research","cost":"small","horizonYears":2},{"id":"idea-data-mcode-payment-condition","kind":"idea","name":"No mCODE, no payment: tie oncology reimbursement to a minimal structured record","aka":[],"tldr":"Hospitals would only be paid for cancer treatment if they record a small, standard set of facts (diagnosis, stage, biomarkers, treatment, outcome) in a shared format that any computer can read.","summary":"mCODE (minimal Common Oncology Data Elements) is an HL7 FHIR implementation guide of roughly 90 elements covering the cancer patient, disease, genomics, treatment and outcomes. Adoption is voluntary and patchy. The proposal is for Medicare, the NHS and national insurers to make conformant mCODE capture a condition of payment for systemic anticancer therapy, phased over three years, mirroring how Meaningful Use forced EHR adoption in the US and how the NHS Systemic Anti-Cancer Therapy (SACT) dataset made chemotherapy reporting near-universal in England.","asOf":"2026-09-08","links":[{"label":"mCODE implementation guide (HL7)","url":"https://hl7.org/fhir/us/mcode/"},{"label":"NHS SACT dataset","url":"https://digital.nhs.uk/ndrs/data/data-sets/sact"}],"tags":[],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["real-world-evidence"],"trials":[],"people":[],"bottlenecks":["b-data-silos","b-real-world-evidence"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Within three years of a payment mandate, more than 90 percent of treated patients in the paying system will have a complete, conformant mCODE record, and the time to answer a standard real-world question (for example, first-line treatment patterns for a new approval) will fall from years to weeks.","rationale":"Payment conditions are the only lever that has ever produced near-complete clinical datasets at national scale: SACT in England and Meaningful Use in the US both worked where voluntary standards did not. mCODE already has vendor implementations (Epic, Flatiron, Varian) so the marginal cost is configuration, not invention.","test":"A two-year pilot in one payer region (a US state Medicaid programme or one NHS integrated care system) paying a small per-record bonus for conformant mCODE capture, with completeness and timeliness audited against the SACT or registry gold standard; compare completeness with matched control regions.","maturity":"speculative","actor":"payer","cost":"medium","horizonYears":3},{"id":"idea-tr2-irb-results-gate","kind":"idea","name":"No new trial approval until the sponsor has reported its old ones","aka":[],"tldr":"Ethics committees should check whether a sponsor has published the results of its previous finished trials before approving the next one.","summary":"Ethics review has a legitimate interest in results reporting: participants consent partly on the promise that knowledge will be shared. Requiring sponsors to certify, and committees to verify via registry, that all trials completed more than two years ago have posted results, with approval withheld otherwise, would create the strongest incentive available without new legislation.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Failures are hidden): Anderson et al., Compliance with results reporting at ClinicalTrials.gov (NEJM 2015)","url":"https://doi.org/10.1056/NEJMsa1409364"}],"tags":[],"related":["clinicaltrials-gov","idea-tr2-fdaaa-enforcement"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-negative-results"],"keyPapers":["paper-anderson-n-engl-j-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Institutions adopting the gate will see completed-trial results posting exceed 95% within two years, and non-adopting peers will remain below 80%.","rationale":"Ethics committees already condition approval on prior conduct (for example investigator training). The World Medical Association's Declaration of Helsinki names results publication as an ethical duty.","test":"Pilot at five academic institutions with a shared registry lookup tool; compare posting rates with matched institutions.","maturity":"speculative","actor":"regulator","cost":"small","horizonYears":2},{"id":"idea-non-endoscopic-barretts-screening","kind":"idea","name":"Non-endoscopic screening for Barrett's oesophagus and early adenocarcinoma","aka":[],"tldr":"A swallowed sponge on a string can sample the oesophagus in a GP's office. Screen people with chronic reflux to catch adenocarcinoma at a curable stage.","summary":"The proposal is to screen adults with chronic reflux or long-term acid suppression for Barrett's oesophagus and early adenocarcinoma with a swallowed capsule sponge that can be given in a GP's office rather than by endoscopy. Oesophageal adenocarcinoma has a known precursor, a defined at-risk population and curative endoscopic resection for early disease; the missing piece has been an accessible test. In BEST3, reported in the Lancet in 2020, the Cytosponge-TFF3 test detected many more cases of Barrett's than usual care, and the NIHR-funded BEST4 trial now tests whether screening reduces deaths and shifts diagnosis to stage I. Being tested at scale, with EsoGuard methylation markers and AI histology as possible add-ons, it addresses the bottleneck that the hardest cancers are found late.","asOf":"2026-09-07","links":[{"label":"BEST3: Cytosponge-trefoil factor 3 versus usual care to identify Barrett's oesophagus (Lancet 2020)","url":"https://doi.org/10.1016/S0140-6736(20)31099-0"}],"tags":[],"related":[],"cancers":["esophageal"],"sections":[],"technologies":["endoscopic-resection","mced","methylation-profiling"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["barretts-esophagus","stage-shift"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-fitzgerald-lancet"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Offering capsule-sponge screening to adults on long-term acid suppression increases the proportion of oesophageal adenocarcinomas diagnosed at stage I and reduces oesophageal cancer mortality.","rationale":"Adenocarcinoma has a known precursor, a defined at-risk population, and curative endoscopic treatment for early disease; the missing piece is an accessible test.","test":"The BEST4 screening and surveillance arms (mortality and stage-shift endpoints) report in the late 2020s.","maturity":"being-tested-at-scale"},{"id":"idea-reg-open-source-lentiviral-vectors","kind":"idea","name":"Non-profit, open-licence lentiviral vectors and producer cell lines for CAR-T","aka":[],"tldr":"The engineered virus that delivers the CAR gene costs tens of thousands of dollars per patient and is controlled by a few suppliers. A non-profit supplier with open licences would cut that cost sharply.","summary":"Vector is often the single largest material cost in autologous CAR-T and a frequent cause of manufacturing delay; capacity is concentrated among a few contract suppliers and licences are restrictive. Caring Cross and several academic centres have shown that non-profit vector production can supply clinical programmes at a fraction of the cost. The proposal is a foundation-funded vector consortium with stable producer cell lines, a shared plasmid bank for common CARs (CD19, BCMA, CD22) under open licences for non-commercial and low-income-country use, and GMP production at cost.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Manufacturing cost and time for living and radioactive medicines): Hernandez, Prasad & Gellad, Total costs of chimeric antigen receptor T-cell immunotherapy (JAMA Oncology 2018)","url":"https://doi.org/10.1001/jamaoncol.2018.0977"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["car-t"],"targets":["cd19","bcma"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-manufacturing-cell-therapy","b-global-access"],"keyPapers":["paper-hernandez-jama-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Consortium vector supplied at cost reduces vector cost per CAR-T dose to below $5,000 and enables at least ten new academic or LMIC CAR-T programmes to reach the clinic within five years.","rationale":"Vector production is a mature process whose price reflects concentration and licensing more than inherent cost; stable producer lines remove the plasmid transfection step that drives variability and expense.","test":"Fund the consortium to produce GMP vector for three academic CD19 programmes, audit cost per dose and release success rate against commercial contract supply, and count new programmes enabled.","maturity":"early-clinical","actor":"philanthropy","cost":"medium","horizonYears":3},{"id":"idea-reg-non-viral-cart-manufacturing","kind":"idea","name":"Non-viral CAR-T (transposon or CRISPR knock-in) as the default manufacturing route","aka":[],"tldr":"Putting the CAR gene into T cells without a virus removes the most expensive and delay-prone ingredient. Test whether non-viral products match viral ones.","summary":"Transposon systems (piggyBac, Sleeping Beauty) and CRISPR-mediated targeted insertion (for example into the TRAC locus) deliver CAR constructs as DNA or RNA without lentiviral vector, cutting materials cost and removing the vector supply queue; clinical experience exists from Poseida, MD Anderson, Chinese academic groups and others, with an early piggyBac safety signal (lymphoma from integration) in one Australian programme that informs design. The proposal is a head-to-head programme establishing non-viral manufacturing as the default for new autologous and allogeneic CAR-T, with integration-site safety monitoring as a shared standard.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Manufacturing cost and time for living and radioactive medicines): Hernandez, Prasad & Gellad, Total costs of chimeric antigen receptor T-cell immunotherapy (JAMA Oncology 2018)","url":"https://doi.org/10.1001/jamaoncol.2018.0977"}],"tags":[],"related":[],"cancers":["dlbcl"],"sections":[],"technologies":["car-t","allogeneic-cell-therapy"],"targets":["cd19"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct04094311","reliance","talicel-phase-1-2","zuma-1","zuma-7"],"people":[],"bottlenecks":["b-manufacturing-cell-therapy"],"keyPapers":["paper-hernandez-jama-oncol","paper-cd19-dlbcl-am-j-hematol-2021","paper-cd19-dlbcl-clin-cancer-res-2011","paper-cd19-dlbcl-cytotherapy-2020"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Non-viral CD19 CAR-T achieves transduction efficiency, persistence and 12-month response rates non-inferior to lentiviral products at a materials cost per dose lower by at least $15,000, with no excess of integration-related malignancy over five years of follow-up.","rationale":"Vector supply is a scheduling and cost bottleneck unrelated to the biology of the product; targeted insertion may also improve product consistency by placing the CAR under endogenous regulation.","test":"Randomised phase 2 of non-viral versus lentiviral CD19 CAR-T in relapsed lymphoma with manufacturing cost, vein-to-vein time and integration-site analysis as co-primary manufacturing endpoints.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":4},{"id":"idea-acc-nurse-led-chemotherapy-units","kind":"idea","name":"Nurse-led chemotherapy day units with a doctor on a screen","aka":[],"tldr":"Trained nurses following strict written protocols can safely run chemotherapy clinics for common cancers, with an oncologist available by video for decisions and problems.","summary":"Task-shifting delivered HIV treatment to millions when there were no doctors to do it. Chemotherapy for common, protocol-driven indications (early breast cancer, Hodgkin lymphoma, paediatric ALL, cervical chemoradiation) can be delivered by specialist nurses and clinical officers under protocols, with tele-oncology supervision. Partners In Health's Butaro Cancer Centre in Rwanda has run a version of this for more than a decade. The proposal is to define the national protocol set, credential the roles, and measure outcomes at scale.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Most of the world has almost no cancer care): WHO fact sheet, Cancer","url":"https://www.who.int/news-room/fact-sheets/detail/cancer"}],"tags":[],"related":[],"cancers":["breast-hr-positive","hodgkin-lymphoma","all-leukemia","cervical"],"sections":["chemotherapy"],"technologies":["cytotoxic-chemotherapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-global-access","b-workforce"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Nurse-led units under tele-supervision will achieve treatment-completion rates and 30-day treatment-related mortality no worse than physician-led units in the same country for a defined set of curative regimens.","rationale":"The cognitive load of protocolised chemotherapy is in the protocol, not the prescriber. Nurses already manage infusion reactions and toxicity in high-income units; the barrier is legal scope, not competence.","test":"A non-inferiority cluster comparison across ten districts on completion rates, dose-delay rates, febrile neutropenia mortality, and patient-reported experience, with an independent safety committee.","maturity":"being-tested-at-scale","actor":"clinic","cost":"medium","horizonYears":3},{"id":"idea-acc-nurse-led-follow-up-clinics","kind":"idea","name":"Nurse-led follow-up clinics for survivors, freeing oncologists for active treatment","aka":[],"tldr":"Most follow-up visits after successful treatment are routine. Nurse practitioners can run them well, giving survivors more time and oncologists more capacity for new patients.","summary":"Follow-up of treated patients consumes a large share of oncology clinic slots but rarely changes management. Nurse-led follow-up has shown equivalent outcomes and higher patient satisfaction in randomised trials in breast, lung, and colorectal cancer. Making this the default model, with explicit re-entry criteria and access to an oncologist, would free specialist time and improve survivorship care quality.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Not enough oncologists, nurses, pathologists, physicists): Yang et al., Projected supply of and demand for oncologists and radiation oncologists through 2025 (JOP 2014)","url":"https://doi.org/10.1200/JOP.2013.001319"}],"tags":[],"related":["idea-acc-risk-stratified-follow-up"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-workforce","b-survivorship"],"keyPapers":["paper-yang-j-oncol-pract"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Shifting routine follow-up to nurse-led clinics will free at least 20% of oncologist clinic capacity and will not delay detection of recurrence, measured by stage at recurrence and time from symptom to diagnosis.","rationale":"Randomised evidence already exists for equivalence; adoption is limited by payment models and professional custom, which are addressable.","test":"A pragmatic implementation across a regional network with capacity, recurrence detection, and patient-reported outcomes as endpoints.","maturity":"being-tested-at-scale","actor":"clinic","cost":"small","horizonYears":2},{"id":"idea-shared-kras-vaccine-adjuvant","kind":"idea","name":"Off-the-shelf KRAS vaccines after pancreatic cancer surgery","aka":[],"tldr":"Almost every pancreatic cancer shares one of a handful of KRAS mutations. A pre-made vaccine against them could be given to every patient after surgery.","summary":"Almost every pancreatic cancer carries one of a handful of KRAS mutations, so this idea gives a pre-made KRAS vaccine to every patient after surgery, enriching for MRD-positive disease. Tumour burden is low after resection, the neoantigen is shared, ctDNA can enrich and monitor, and RAS inhibitors such as daraxonrasib may increase antigen presentation. ELI-002 7P from Elicio induced KRAS-specific T cells in phase 1 and is in the randomised AMPLIFY-7P phase 2, whereas personalised vaccines such as autogene cevumeran work but take weeks and cost more. The test is a phase 2/3 with ctDNA-positive enrichment and a recurrence-free survival endpoint. At early-clinical maturity it addresses the bottleneck The undruggable drivers.","asOf":"2026-09-04","links":[{"label":"Pant et al., AMPLIFY-201: lymph-node-targeted mutant KRAS amphiphile vaccine in pancreatic and colorectal cancer (Nature Medicine 2024)","url":"https://doi.org/10.1038/s41591-023-02760-3"}],"tags":[],"related":[],"cancers":["pancreatic","colorectal"],"sections":[],"technologies":["shared-antigen-vaccine","mrd-testing","kras-inhibitors"],"targets":["kras"],"drugs":["daraxonrasib","autogene-cevumeran"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["codebreak-300","nct07252232","nct07491445","nct07621718","rasolute-302"],"people":[],"bottlenecks":[],"keyPapers":["paper-pant-nat-med","paper-kras-colorectal-j-clin-oncol-2008","paper-kras-colorectal-j-clin-oncol-2011","paper-kras-colorectal-j-clin-oncol-2010"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Adjuvant KRAS peptide/mRNA vaccination reduces recurrence in resected PDAC with MRD-positive disease, with T-cell response magnitude predicting benefit.","rationale":"Shared neoantigen, low tumour burden post-surgery, ctDNA to enrich and monitor; complements RAS inhibitors that may increase antigen presentation.","test":"Run a phase 2/3 with ctDNA-positive enrichment and an RFS endpoint; explore combination with daraxonrasib.","maturity":"early-clinical"},{"id":"idea-bio2-nk-cells-for-mrd","kind":"idea","name":"Off-the-shelf natural killer cells to sweep up residual disease","aka":[],"tldr":"Donor immune cells that need no matching could be given as short courses to clear the few cancer cells left after surgery, when the target is smallest.","summary":"Allogeneic natural killer and CAR-NK products have been limited by short persistence and modest activity against bulky solid tumours, but persistence matters far less when the target is a handful of disseminated cells. Combined with a cytokine support agent, repeat dosing in the molecular residual disease window is a rational use of a product class that has struggled in advanced disease.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Dormant cells and minimal residual disease): Tie et al., ctDNA analysis guiding adjuvant therapy in stage II colon cancer (NEJM 2022)","url":"https://doi.org/10.1056/NEJMoa2200075"}],"tags":[],"related":[],"cancers":["colorectal","tnbc"],"sections":[],"technologies":["car-nk-macrophage","allogeneic-cell-therapy","mrd-testing"],"targets":[],"drugs":["nogapendekin-alfa"],"companies":["nkarta","fate-therapeutics","immunitybio"],"institutions":[],"pathways":[],"terms":["mrd","crs"],"trials":[],"people":[],"bottlenecks":["b-dormancy-mrd","b-manufacturing-cell-therapy"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Repeat-dosed allogeneic NK cell therapy converts ctDNA-positive post-surgical patients to ctDNA-negative more often than standard care, with no cytokine release syndrome above grade 2.","rationale":"NK cells kill single cells in circulation and marrow efficiently and do not require antigen presentation or HLA matching, so they suit a low-burden, wide-antigen setting. Off-the-shelf supply makes rapid treatment after a positive test feasible.","test":"A phase 2 single-arm study in ctDNA-positive colorectal or breast cancer with molecular clearance at six months as primary endpoint, and paired marrow sampling to confirm disseminated cell clearance.","maturity":"preclinical-evidence","actor":"industry","cost":"medium","horizonYears":7},{"id":"idea-prev-population-germline-screening-at-30","kind":"idea","name":"Offer everyone at 30 a test for the cancer genes that matter","aka":[],"tldr":"Most people with BRCA or Lynch mutations do not know until they get cancer. Testing everyone once for a short list of high-impact genes would find them in time to prevent it.","summary":"Population screening for CDC Tier 1 conditions (BRCA1/2, Lynch syndrome, familial hypercholesterolaemia) has been piloted in Geisinger MyCode, the Healthy Nevada Project, and Jewish BRCA programmes, finding that most carriers would not meet family-history criteria. Propose a national programme at age 30 with tiered disclosure and linked prevention pathways.","asOf":"2026-09-08","links":[{"label":"Healthy Nevada Project","url":"https://healthynv.org"},{"label":"Our Future Health","url":"https://ourfuturehealth.org.uk"}],"tags":[],"related":[],"cancers":[],"sections":["prevention"],"technologies":["germline-testing"],"targets":["brca"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-hereditary-risk"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Population screening identifies at least half of carriers who would otherwise be missed by family-history criteria, at a cost per QALY under $50,000.","rationale":"Family-history criteria miss about half of carriers, and test costs have fallen below cost-effectiveness thresholds in UK and US modelling.","test":"Regional pilot in 100,000 people with uptake, carrier yield, and prevention uptake as endpoints.","maturity":"being-tested-at-scale","actor":"policy","cost":"large","horizonYears":5},{"id":"idea-prev-hpv-vaccinate-at-screening","kind":"idea","name":"Offer HPV vaccination to women when they come for cervical screening or treatment","aka":[],"tldr":"Adult women who missed the vaccine could get it at their screening visit. Vaccination around treatment for precancer also seems to cut recurrence.","summary":"Observational data and the NOVEL trial suggest HPV vaccination at the time of excisional treatment for CIN2+ reduces recurrence. Propose a screen-and-vaccinate offer for women aged 25-45 at screening, with an RCT of recurrence in treated women and cost-effectiveness modelling for the screened population.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Prevention we already have is not deployed): Islami et al., Proportion of cancer attributable to modifiable risk factors (CA 2018)","url":"https://doi.org/10.3322/caac.21440"}],"tags":[],"related":[],"cancers":["cervical"],"sections":["prevention"],"technologies":["hpv-vaccine"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption"],"keyPapers":["paper-islami-ca-cancer-j-clin"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Vaccination at CIN treatment reduces CIN2+ recurrence by at least half, and vaccination at screening reduces incident HPV16/18 infection by at least 40% in unvaccinated 25-45-year-olds.","rationale":"Prevents reinfection and uses an existing clinical contact.","test":"1,500-woman RCT in treated women; pragmatic uptake pilot in screening clinics.","maturity":"early-clinical","actor":"clinic","cost":"medium","horizonYears":4},{"id":"idea-prev-blood-crc-test-for-non-responders","kind":"idea","name":"Offer the blood test for bowel cancer only to people who refuse stool tests or colonoscopy","aka":[],"tldr":"Blood tests for bowel cancer miss most precancerous polyps, so they should not replace stool tests. But for the third of people who never do any screening, a blood test may beat nothing.","summary":"Shield (Guardant) is FDA-approved with about 83% sensitivity for colorectal cancer but around 13% for advanced adenomas; the concern is substitution away from FIT and colonoscopy. Propose a randomised trial in persistent non-responders: blood test offer versus repeat FIT offer, endpoint stage I-II cancers detected per 1,000 invited.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The hardest cancers are found late): Crosby et al., Early detection of cancer (Science 2022)","url":"https://doi.org/10.1126/science.aay9040"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":["early-detection"],"technologies":["liquid-biopsy"],"targets":[],"drugs":["shield"],"companies":["guardant-health","freenome"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-early-detection","b-prevention-adoption"],"keyPapers":["paper-crosby-science"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Offering a blood test to non-responders raises participation by at least 20 percentage points and yields more early-stage cancers per 1,000 invited than a further FIT invitation.","rationale":"Uptake, not test accuracy, drives population benefit; a moderately sensitive test with high uptake beats an excellent test nobody takes.","test":"Run a 20,000-person RCT in a programme with good registry linkage.","maturity":"early-clinical","actor":"payer","cost":"medium","horizonYears":3},{"id":"idea-data-offline-cds-lmic-generalists","kind":"idea","name":"Offline decision support for generalists treating common cancers in low-resource settings","aka":[],"tldr":"A phone app that works without internet and guides a general doctor or nurse through diagnosing and treating common cancers with the drugs actually available locally.","summary":"In much of the world cancer is treated by generalists with no oncologist within reach. Resource-stratified guidelines (NCCN Harmonized Guidelines for sub-Saharan Africa, ASCO resource-stratified guidelines, WHO essential medicines) exist as documents. Encoding them as offline-capable, computable decision support with local formulary awareness, dose calculators and referral criteria, endorsed by WHO and ministries, would put them at the point of care.","asOf":"2026-09-08","links":[{"label":"NCCN Harmonized Guidelines for Sub-Saharan Africa","url":"https://www.nccn.org/global/what-we-do/harmonized-guidelines"}],"tags":[],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["nccn","asco"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-knowledge-diffusion","b-global-access","b-workforce"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Generalists using offline decision support will deliver guideline-concordant treatment in a substantially higher share of cases and reduce serious dosing errors versus usual practice.","rationale":"Offline clinical decision support for HIV and maternal health improved adherence to protocols in LMIC trials; cancer guidance is more complex but the delivery mechanism is proven.","test":"Cluster-randomise 20 district hospitals in two countries to the app or usual care for breast and cervical cancer; measure concordance and dosing errors over 12 months.","maturity":"early-clinical","actor":"philanthropy","cost":"medium","horizonYears":3},{"id":"idea-moon-oncology-hospital-at-home","kind":"idea","name":"Oncology hospital-at-home with remote monitoring for toxicity","aka":[],"tldr":"Manage fevers, dehydration and other treatment side-effects at home with visiting nurses, wearables and video, instead of admitting people to hospital wards.","summary":"Hospital-at-home programmes for medical conditions reduce cost and complications with equal or better outcomes. Oncology pilots (including for neutropenic fever in low-risk patients and post-chemotherapy support) show feasibility. The proposal is a scaled model combining patient-reported outcomes, wearable vital signs, home intravenous therapy and same-day nurse response, integrated with the oncology team, evaluated for safety and patient preference.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Toxicity and quality of life are undervalued): Di Maio et al., Symptomatic toxicities experienced during anticancer treatment: agreement between patient and physician reporting (JCO 2015)","url":"https://doi.org/10.1200/JCO.2014.57.9334"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol","b-care-fragmentation"],"keyPapers":["paper-di-maio-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Hospital-at-home reduces inpatient bed-days for toxicity by a third with no increase in mortality or intensive care admission and higher patient-reported satisfaction.","rationale":"Most toxicity admissions are for monitoring and supportive therapy that do not need a ward; being at home preserves function and reduces hospital-acquired harm.","test":"Randomised trial of hospital-at-home versus admission for defined toxicity presentations in patients meeting safety criteria; primary endpoint composite of death, ICU admission and readmission at 30 days.","maturity":"early-clinical","actor":"clinic","cost":"medium","horizonYears":3},{"id":"idea-acc-oncology-pharmacist-prescribing","kind":"idea","name":"Oncology pharmacists as protocol prescribers for supportive care and dose adjustments","aka":[],"tldr":"Let specially trained cancer pharmacists prescribe anti-sickness drugs, growth-factor support and routine dose adjustments under protocols, freeing oncologists for decisions only they can make.","summary":"Oncology pharmacists already check every chemotherapy prescription; in several countries (UK, parts of Canada and the US) they hold independent or collaborative prescribing rights for supportive medicines and protocol dose modifications. Extending this model widely, with a defined competency framework, removes a large fraction of routine prescribing from oncologists' clinics and shortens chair waits caused by prescription queries.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Not enough oncologists, nurses, pathologists, physicists): Yang et al., Projected supply of and demand for oncologists and radiation oncologists through 2025 (JOP 2014)","url":"https://doi.org/10.1200/JOP.2013.001319"}],"tags":[],"related":[],"cancers":[],"sections":["chemotherapy","supportive-care"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-workforce","b-care-fragmentation"],"keyPapers":["paper-yang-j-oncol-pract"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Units with pharmacist protocol prescribing will reduce oncologist time per chemotherapy cycle by at least 20% and reduce day-of-treatment prescription delays by half, with no increase in medication errors.","rationale":"Pharmacists are the profession with the deepest drug-dosing training; collaborative prescribing has shown equivalent safety in anticoagulation, diabetes, and HIV care.","test":"A twelve-month before-and-after study across five day units with time-motion measurement, delay logs, and an independent error audit.","maturity":"early-clinical","actor":"regulator","cost":"small","horizonYears":2},{"id":"idea-acc-mainstream-tele-genetic-counselling","kind":"idea","name":"Oncology teams order germline tests; tele-genetic counsellors handle the results","aka":[],"tldr":"There are too few genetic counsellors to see every patient who should have an inherited-risk test. Let the cancer team order the test with a short consent script, and use video counsellors for those with results that matter.","summary":"Mainstreaming, in which oncologists and nurses consent and order germline testing with genetic counselling reserved for positive or complex results, has been shown in ovarian and breast cancer to increase testing rates and shorten time to result without harm. Combined with a pooled tele-genetics service, it would let genetic counsellors cover a much larger population. The proposal is to make this the default pathway with a national tele-genetics roster.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Not enough oncologists, nurses, pathologists, physicists): Yang et al., Projected supply of and demand for oncologists and radiation oncologists through 2025 (JOP 2014)","url":"https://doi.org/10.1200/JOP.2013.001319"}],"tags":[],"related":[],"cancers":["ovarian","breast-hr-positive","colorectal"],"sections":[],"technologies":["germline-testing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-workforce","b-hereditary-risk"],"keyPapers":["paper-yang-j-oncol-pract"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Mainstreaming plus tele-genetics will increase germline testing among eligible patients from under 40% to above 80% within two years, while keeping counsellor time per tested patient below a third of the traditional pathway.","rationale":"Guideline-eligible testing rates are low everywhere because of counsellor bottlenecks; mainstreaming studies show the workflow is safe and acceptable to patients.","test":"Stepped implementation across a regional network measuring testing rate, time to result, cascade testing of relatives, and patient-reported distress.","maturity":"being-tested-at-scale","actor":"clinic","cost":"small","horizonYears":2},{"id":"idea-bio2-oncolytic-regulated-il12","kind":"idea","name":"Oncolytic viruses that make interleukin-12 only inside the tumour","aka":[],"tldr":"Interleukin-12 is an immune-stimulating cytokine that caused severe toxicity when injected into the bloodstream in the 1990s and was abandoned. An oncolytic herpes or adenovirus carrying the interleukin-12 gene under a drug-inducible promoter makes it only inside the tumour, keeping exposure local; trials include recurrent glioblastoma.","summary":"Systemic interleukin-12 caused severe toxicity in the 1990s and was abandoned. Oncolytic herpes and adenovirus vectors carrying interleukin-12 under regulated or drug-inducible promoters, including trials in recurrent glioblastoma, keep exposure local and measurable. Combining a regulated cytokine payload with checkpoint blockade is a rational path to converting cold tumours.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Cold tumours and the immunosuppressive microenvironment): Haslam & Prasad, Estimation of the percentage of US patients eligible for and responding to checkpoint inhibitors (JAMA Netw Open 2019)","url":"https://doi.org/10.1001/jamanetworkopen.2019.2535"}],"tags":[],"related":[],"cancers":["glioblastoma","melanoma","urothelial"],"sections":[],"technologies":["oncolytic-virus","cytokine-therapy","checkpoint-inhibitor"],"targets":[],"drugs":["talimogene-laherparepvec","vusolimogene-oderparepvec","cretostimogene","nadofaragene-firadenovec"],"companies":["replimune","cg-oncology"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["kevin-harrington"],"bottlenecks":["b-tme-immunosuppression","b-brain-delivery"],"keyPapers":["paper-haslam-jama-netw-open"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A regulated intratumoural interleukin-12 payload achieves tumour-to-plasma cytokine ratios above 100 and produces T-cell infiltration in previously cold lesions, without dose-limiting systemic toxicity.","rationale":"The failure of interleukin-12 was pharmacokinetic, not immunological, and local delivery is exactly the right fix. Oncolytic products are already approved in melanoma and bladder cancer, so the manufacturing and regulatory route exists.","test":"Dose-escalation with paired biopsies and matched plasma cytokine measurement, reporting tumour-to-plasma ratio and change in CD8 density as the primary endpoints, before efficacy expansion.","maturity":"early-clinical","actor":"industry","cost":"medium","horizonYears":7},{"id":"idea-car-t-replaces-transplant","kind":"idea","name":"One CAR-T infusion instead of autologous transplant","aka":[],"tldr":"Replace high-dose melphalan and stem-cell rescue with a single infusion of the patient's engineered T cells after induction.","summary":"Instead of high-dose melphalan and stem cell rescue, this idea would consolidate newly diagnosed multiple myeloma with a single infusion of ciltacabtagene autoleucel after quadruplet induction. The rationale is that transplant adds progression-free but not overall survival over triplets in DETERMINATION, that cilta-cel improved survival in the second line in CARTITUDE-4, and that earlier use finds fitter T cells and lower tumour burden. The hypothesis is that cilta-cel consolidation gives superior sustained MRD negativity and progression-free survival versus transplant without excess second cancers. CARTITUDE-6 (EMagine) randomises Dara-VRd then cilta-cel against Dara-VRd then transplant, and CARTITUDE-5 tests cilta-cel where transplant is not planned; it is being tested at scale.","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT04923893: CARTITUDE-5","url":"https://clinicaltrials.gov/study/NCT04923893"},{"label":"ClinicalTrials.gov NCT04181827: CARTITUDE-4","url":"https://clinicaltrials.gov/study/NCT04181827"}],"tags":[],"related":[],"cancers":["multiple-myeloma"],"sections":[],"technologies":["car-t","autologous-stem-cell-transplant"],"targets":[],"drugs":["ciltacabtagene-autoleucel"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["cartitude-5","cartitude-4"],"people":[],"bottlenecks":[],"keyPapers":["paper-ciltacabtagene-autoleucel-multiple-myeloma-front-immunol-2022","paper-ciltacabtagene-autoleucel-multiple-myeloma-j-clin-oncol-2023","paper-ciltacabtagene-autoleucel-multiple-myeloma-clin-cancer-res-2024"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Cilta-cel consolidation after quadruplet induction gives superior sustained MRD negativity and PFS versus transplant, with acceptable neurotoxicity and no second-malignancy excess.","rationale":"Transplant adds PFS but not OS over triplets (DETERMINATION); CAR-T in second line gave OS HR 0.55; earlier use finds fitter T cells and lower tumour burden.","test":"CARTITUDE-6 answers this with its primary endpoints (sustained MRD-negative CR, PFS), backed by long-term second-malignancy surveillance.","maturity":"being-tested-at-scale"},{"id":"idea-data-open-deidentification-pipeline","kind":"idea","name":"One certified open-source de-identification pipeline for scans and slides","aka":[],"tldr":"Build and certify a single free tool that strips names and identifying marks from cancer scans and pathology slides, so every hospital stops writing its own.","summary":"Every institution that shares imaging builds or buys its own DICOM de-identification, with inconsistent handling of burned-in text, private tags and slide label images. The Cancer Imaging Archive has curation experience and there are open tools (for example the RSNA anonymizer and CTP), but no certified reference implementation for whole-slide images or radiotherapy objects. The proposal funds a maintained open pipeline with a public test corpus of adversarial cases and an independent certification.","asOf":"2026-09-08","links":[{"label":"The Cancer Imaging Archive","url":"https://www.cancerimagingarchive.net/"}],"tags":[],"related":["tcia"],"cancers":[],"sections":["ai-computation"],"technologies":["ct","mri","digital-pathology-ai"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-data-silos","b-ai-validation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A certified reference pipeline adopted by more than 50 centres will cut time-to-share for a new imaging cohort from months to weeks and reduce identified leakage incidents to near zero in audits.","rationale":"De-identification uncertainty is one of the most common reasons legal teams block imaging release; a certified standard shifts the risk decision from each hospital to a shared, audited tool.","test":"Run the pipeline and three institutional pipelines against a red-team corpus of 5,000 images with planted identifiers; publish leak rates. Then measure adoption and release times among centres that switch.","maturity":"early-clinical","actor":"engineering","cost":"small","horizonYears":2},{"id":"idea-reg-global-trial-application-portal","kind":"idea","name":"One clinical trial application accepted by regulators in every major region","aka":[],"tldr":"Starting a cancer trial in ten countries means ten applications and ten ethics reviews. One shared application and a common ethics template would start trials months sooner.","summary":"The EU's Clinical Trials Information System allows a single application across member states. The proposal is to extend the same logic internationally: a common application dataset (protocol, IMP dossier, investigator brochure, consent template) accepted by FDA, MHRA, PMDA, NMPA, TGA and Health Canada with country-specific fields limited to sites and local consent language, and a harmonised ethics review template built on CIOMS and WHO guidance. Multiregional oncology trials would gain months per country.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Regulatory divergence between regions): FDA Oncology Center of Excellence, Project Orbis","url":"https://www.fda.gov/about-fda/oncology-center-excellence/project-orbis"}],"tags":[],"related":["eudract-ctis","clinicaltrials-gov"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-regulatory-fragmentation","b-trial-enrolment"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A shared application dataset cuts the median time from first to last country activation in multiregional oncology phase 3 trials by at least four months and reduces sponsor start-up cost per country by half.","rationale":"Country start-up is the largest single contributor to trial duration variance. The scientific content of applications is identical; only the forms differ. CTIS shows that a shared system works across 27 legal systems.","test":"Pilot with ICH members on ten multiregional oncology trials using a common application dataset; measure first-to-last activation interval against the sponsors' own historical benchmarks.","maturity":"speculative","actor":"regulator","cost":"medium","horizonYears":5},{"id":"idea-nl-ketogenic-gbm-definitive-trial","kind":"idea","name":"One definitive ketogenic diet trial in glioblastoma, then stop","aka":[],"tldr":"Patients with brain tumours are sold ketogenic diets on the strength of mouse data and small feasibility studies. A single adequately powered trial with dietitian support would either prove it or let clinicians say clearly that it does not work.","summary":"Fifteen years of feasibility studies have shown ketogenic diets are tolerable for a few months in glioblastoma and have not shown efficacy. Because the diet is marketed directly to patients and is a common reason for conflict with treating teams, the cost of not knowing is high. No company will fund a diet trial; a philanthropic or cooperative-group trial with adherence biomarkers (blood ketones), a pre-registered stopping rule and a commitment to publish either way is the appropriate instrument.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Misinformation and unproven therapies): Johnson et al., Cancer misinformation and harmful information on Facebook and other social media (JNCI 2022)","url":"https://doi.org/10.1093/jnci/djab141"}],"tags":[],"related":[],"cancers":["glioblastoma"],"sections":["nutrition-lifestyle"],"technologies":["ketogenic-diet-glioblastoma","metabolic-therapy","nutrition-screening-mnt"],"targets":[],"drugs":["temozolomide"],"companies":[],"institutions":[],"pathways":[],"terms":["warburg-effect-diet-claims","unproven-diet-claims","warburg-effect"],"trials":["ergo2"],"people":[],"bottlenecks":["b-misinformation","b-negative-results","b-funding-allocation"],"keyPapers":["paper-johnson-j-natl-cancer-inst"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A supervised ketogenic diet maintained for six months alongside standard chemoradiation and temozolomide does not improve overall survival in newly diagnosed glioblastoma compared with a standard healthy diet (null hypothesis to be tested with power to detect a 3-month median difference).","rationale":"The Warburg rationale is plausible but tumours adapt to use ketones and lactate; steroids undermine ketosis; ERGO2 was null but brief. A definitive answer protects patients from an intervention with real costs (weight loss, quality of life, expense) if it fails, and mobilises adoption if it works.","test":"Randomised phase 2/3 (about 300 patients) in newly diagnosed IDH-wildtype glioblastoma, stratified by MGMT status and steroid use, with dietitian-delivered ketogenic diet vs Mediterranean-style diet, ketone-verified adherence, OS primary endpoint, quality of life and body composition secondary, and pre-registered publication regardless of result.","maturity":"early-clinical","actor":"philanthropy","cost":"medium","horizonYears":5},{"id":"idea-tr2-pdl1-digital-calibration","kind":"idea","name":"One digital PD-L1 scale that maps across all the competing assays","aka":[],"tldr":"There are several different PD-L1 tests, each tied to a different drug, and they disagree. A single digitally calibrated scale would let any lab's result be translated into any drug's cut-off.","summary":"22C3, SP263, 28-8 and SP142 assays, with tumour proportion score, combined positive score and immune-cell scoring, produce different positivity for the same tumour. The Blueprint project showed partial concordance. A quantitative digital pathology reference (stain intensity and cell counts calibrated on shared reference materials) could express each assay on a common scale, so a lab running one assay could report validated equivalents for the cut-offs used in each drug label.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Biomarkers are not validated or standardised): Fernandez et al., Examination of low ERBB2 protein expression in breast cancer tissue (JAMA Oncology 2022)","url":"https://doi.org/10.1001/jamaoncol.2021.7239"}],"tags":[],"related":["paige","pathai"],"cancers":[],"sections":[],"technologies":["digital-pathology-ai","histopathology-ihc","checkpoint-inhibitor"],"targets":["pdl1"],"drugs":["pembrolizumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-biomarker-validation","b-immunotherapy-response"],"keyPapers":["paper-fernandez-jama-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A calibrated digital PD-L1 score will predict benefit from PD-1 blockade at least as well as each label-specified assay in retrospective analyses of trial samples, allowing a single test to serve multiple drugs.","rationale":"Digital quantification removes reader variability, and reference materials remove staining variability, the two dominant sources of disagreement.","test":"Stain trial samples from two registrational immunotherapy trials with all four assays plus the digital scale; compare predictive performance against outcomes.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":3},{"id":"idea-tr2-platform-single-ethics","kind":"idea","name":"One ethics approval and one consent form for a platform trial across countries","aka":[],"tldr":"Adding a new arm to an international platform trial currently needs approval in every country again. A single, pre-agreed process would let arms open in weeks.","summary":"The EU Clinical Trials Regulation and its CTIS portal, the US single IRB mandate and the UK combined review are steps towards this, but arm additions to platforms still trigger substantial amendments reviewed separately. A recognised 'platform amendment' pathway with pre-approved master consent language and a 30-day review clock for new arms would make international platforms practical.","asOf":"2026-09-08","links":[{"label":"EU Clinical Trials Information System","url":"https://euclinicaltrials.eu/"}],"tags":[],"related":["eudract-ctis","clinicaltrials-gov"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["basket-umbrella-platform"],"trials":[],"people":[],"bottlenecks":["b-combination-space","b-regulatory-fragmentation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A dedicated platform amendment pathway reduces median time to open a new arm across five countries from over twelve months to under three.","rationale":"The adaptive platform trial community has documented arm-opening delays as the main limit on throughput. Regulatory harmonisation initiatives (ICH E6(R3), Project Orbis) show that reviewers can share work.","test":"Pilot with one international academic platform under CTIS plus MHRA and one US single IRB; time arm openings before and after.","maturity":"early-clinical","actor":"regulator","cost":"small","horizonYears":3},{"id":"idea-reg-joint-regulator-hta-plan","kind":"idea","name":"One evidence plan agreed by regulator and payer before the pivotal trial","aka":[],"tldr":"Regulators want proof a drug works; payers want proof it is worth the price. Agreeing both requirements at once would stop drugs being approved but then not paid for.","summary":"The EU HTA Regulation (applying to oncology from January 2025) introduces joint clinical assessments and joint scientific consultations alongside EMA advice. The proposal is to extend this to a single pre-pivotal evidence plan involving the regulator, national HTA bodies (NICE, G-BA, HAS, CADTH, PBAC) and ideally large payers, agreeing comparator, endpoints, patient-reported outcomes and real-world evidence commitments so that one trial serves both approval and reimbursement.","asOf":"2026-09-08","links":[{"label":"EU HTA Regulation","url":"https://health.ec.europa.eu/health-technology-assessment/regulation-health-technology-assessment_en"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-regulatory-fragmentation","b-drug-pricing"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Products developed under a joint regulator-HTA plan reach reimbursement a median of nine months sooner after approval and receive fewer HTA requests for additional comparative evidence.","rationale":"The approval-to-reimbursement gap in Europe averages well over a year and is driven largely by comparator and endpoint mismatches that were avoidable at design. Aligning demands upstream is cheaper than indirect comparisons downstream.","test":"Track reimbursement timelines for oncology products that used joint scientific consultations against contemporaneous products that did not; extend joint plans to include NICE and CADTH for a pilot of ten products.","maturity":"early-clinical","actor":"payer","cost":"small","horizonYears":4},{"id":"idea-reg-single-paediatric-plan","kind":"idea","name":"One global paediatric cancer development plan instead of separate FDA and EMA plans","aka":[],"tldr":"Companies must agree separate plans for testing new cancer drugs in children with US and European regulators. A single agreed plan would get children access sooner.","summary":"The EU Paediatric Investigation Plan and the US Pediatric Study Plan (strengthened by the RACE for Children Act) are negotiated separately and often specify different trials, ages or endpoints. The ACCELERATE platform and the FDA-EMA Common Commentary have begun to align them. The proposal is a single joint plan with one decision letter and reciprocal deferral and waiver decisions, extended to PMDA and Health Canada, so a paediatric oncology programme is designed once.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Regulatory divergence between regions): FDA Oncology Center of Excellence, Project Orbis","url":"https://www.fda.gov/about-fda/oncology-center-excellence/project-orbis"}],"tags":[],"related":[],"cancers":["neuroblastoma","all-leukemia"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-regulatory-fragmentation","b-rare-cancers"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A single joint plan reduces the number of distinct paediatric trials required per new oncology molecule and shortens the time from adult approval to a paediatric label by at least two years.","rationale":"Paediatric cancer populations are tiny; duplicate trials for the same molecule in different regions compete for the same children and often fail to enrol. One plan with shared enrolment removes that competition.","test":"Compare paediatric labelling timelines for molecules whose plans were aligned through the Common Commentary process with those that were not; then pilot formal joint plans for the next 15 molecules with paediatric relevance.","maturity":"early-clinical","actor":"regulator","cost":"small","horizonYears":4},{"id":"idea-moon-rare-cancer-global-network","kind":"idea","name":"One global rare cancer network with n-of-1 and Bayesian trial frameworks","aka":[],"tldr":"Rare cancers are collectively common but each is too rare for normal trials. Link every rare cancer patient worldwide into one network with registries and trial designs built for small numbers.","summary":"Rare cancers make up roughly a quarter of cancer diagnoses and have worse survival; each is too infrequent for conventional trials and expertise is scattered. Networks such as EURACAN and the International Rare Cancers Initiative show partial solutions. The proposal is a global federated rare cancer network: a single patient-facing registration and referral pathway, standardised molecular workup, a shared registry with outcomes, and pre-agreed trial frameworks (Bayesian borrowing across related histologies, n-of-1 crossover designs, external control arms from the registry) accepted by regulators for approval decisions.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Rare and paediatric cancers without markets): Gatta et al., Rare cancers are not so rare: the rare cancer burden in Europe (EJC 2011)","url":"https://doi.org/10.1016/j.ejca.2011.08.008"}],"tags":[],"related":[],"cancers":["sarcoma","cholangiocarcinoma","mesothelioma","neuroendocrine"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["curie-nki-eortc"],"institutions":[],"pathways":[],"terms":["basket-umbrella-platform"],"trials":[],"people":[],"bottlenecks":["b-rare-cancers","b-trial-design","b-regulatory-fragmentation"],"keyPapers":["paper-gatta-eur-j-cancer"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"The network doubles the number of rare cancer patients in trials and achieves at least five regulatory approvals in rare histologies within a decade using its trial frameworks.","rationale":"Aggregating small populations across borders is the only route to adequate sample sizes, and regulators have signalled openness to novel designs when data infrastructure is credible.","test":"Launch in sarcoma subtypes and rare gastrointestinal cancers; measure registration coverage, time to trial availability and approvals using network-generated evidence.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":5},{"id":"idea-reg-shared-postmarketing-registry-condition","kind":"idea","name":"One international registry, not one per country, for conditional approvals","aka":[],"tldr":"When a drug is approved early, each country often demands its own follow-up study. A single shared registry would answer the safety questions faster and better.","summary":"Post-authorisation safety and efficacy studies are imposed region by region, producing several small, slow registries for the same product. The proposal is for regulators participating in concurrent review to agree a single international registry protocol (core dataset, governance, open aggregate reporting) as the shared condition, hosted by an academic consortium with sponsor funding. National regulators receive the same interim analyses on the same schedule.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Regulatory divergence between regions): FDA Oncology Center of Excellence, Project Orbis","url":"https://www.fda.gov/about-fda/oncology-center-excellence/project-orbis"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["real-world-evidence"],"trials":[],"people":[],"bottlenecks":["b-regulatory-fragmentation","b-real-world-evidence"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A shared registry reaches the pre-specified sample size for its primary safety question at least twice as fast as the median regional post-authorisation study and results in fewer unmet post-marketing commitments.","rationale":"Rare adverse events and effectiveness in under-represented groups need numbers that no single region accrues quickly; pooling is the only way to answer them within the drug's useful life.","test":"Pilot with the next three concurrent conditional oncology approvals across FDA, EMA and MHRA, with one shared registry each, and compare time to primary analysis with each agency's prior post-authorisation studies.","maturity":"speculative","actor":"regulator","cost":"medium","horizonYears":4},{"id":"idea-data-cross-border-rare-cancer-pool","kind":"idea","name":"One legal framework for pooling rare cancer data across borders","aka":[],"tldr":"Rare cancers are too uncommon for any one country to learn from alone, and national legal differences stop registries pooling records. A standing framework with a common data model, one joint controller agreement, federated queries and GA4GH access passports would let rare cancer registries in the EU, UK, US and Asia be queried as one, then extended to LMIC partners.","summary":"The European Reference Networks (EURACAN, PaedCan) connect rare cancer experts but face national legal differences for data pooling. The proposal is a standing legal and technical framework (common data model, single joint controller agreement, federated queries, GA4GH passports for access) so that rare cancer registries in the EU, UK, US and Asia can be queried as one, extended to LMIC partners.","asOf":"2026-09-08","links":[{"label":"EURACAN","url":"https://euracan.eu/"}],"tags":[],"related":[],"cancers":["sarcoma","mesothelioma"],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-data-silos","b-rare-cancers"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Pooled cross-border rare cancer data will allow outcome analyses on cohorts ten times larger than any national dataset and shorten time to a natural-history baseline for a new rare cancer trial from years to months.","rationale":"For diseases with a few hundred cases a year per country, only pooling produces evidence; the rare-disease field (RD-Connect, Orphanet) has built the legal template.","test":"Pool five national sarcoma registries under the framework; answer three pre-registered questions on sarcoma subtypes with fewer than 100 cases per country per year.","maturity":"early-clinical","actor":"policy","cost":"medium","horizonYears":3},{"id":"idea-prev-chemoprevention-master-protocol","kind":"idea","name":"One master trial for cancer prevention drugs across many precancers","aka":[],"tldr":"Prevention drug trials run separately in each precancer and are slow. One master protocol with shared infrastructure across Barrett's oesophagus, oral leukoplakia, lung nodules and pancreatic cysts, using regression as an intermediate endpoint and adding or dropping arms adaptively, would test several drugs at once.","summary":"Each precursor cohort has small stand-alone chemoprevention trials. Propose a master protocol with shared infrastructure, biomarker-defined precursor cohorts, intermediate endpoints (regression, progression-free interval), and adaptive arm addition and dropping, funded jointly by NCI's prevention network and philanthropy.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Prevention we already have is not deployed): Islami et al., Proportion of cancer attributable to modifiable risk factors (CA 2018)","url":"https://doi.org/10.3322/caac.21440"}],"tags":[],"related":[],"cancers":[],"sections":["prevention"],"technologies":["chemoprevention"],"targets":[],"drugs":[],"companies":[],"institutions":["nci"],"pathways":[],"terms":["basket-umbrella-platform"],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption","b-trial-design"],"keyPapers":["paper-islami-ca-cancer-j-clin"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A platform cuts time from candidate agent to phase 2 readout from about eight years to about three and tests at least three times more agents per dollar than stand-alone trials.","rationale":"Platform trials (I-SPY, STAMPEDE) achieved this in treatment; precancers share biology such as chronic inflammation and immune escape.","test":"Launch with three precursor cohorts and four agents; evaluate throughput at four years.","maturity":"speculative","actor":"research","cost":"large","horizonYears":5},{"id":"idea-acc-remote-medical-physics-qa","kind":"idea","name":"One medical physicist covering many radiotherapy machines through remote quality assurance","aka":[],"tldr":"Medical physicists, who keep radiotherapy machines accurate and safe, are in even shorter supply than oncologists in under-resourced systems. Routine linac quality assurance is now largely automated and log-file based, so one physicist could review it remotely while trained radiation therapists take the measurements, covering three to five machines once regulators define the supervision standard.","summary":"Routine linac quality assurance (output constancy, imaging alignment, plan verification) is increasingly automated and log-file based. A physicist can review these remotely while trained radiation therapists perform the physical measurements. Coupled with remote plan checks and periodic on-site audits, this model could let one physicist supervise three to five machines across sites. Regulators and professional bodies would need to define the supervision standard.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Not enough oncologists, nurses, pathologists, physicists): Yang et al., Projected supply of and demand for oncologists and radiation oncologists through 2025 (JOP 2014)","url":"https://doi.org/10.1200/JOP.2013.001319"}],"tags":[],"related":["idea-acc-remote-planning-hubs"],"cancers":[],"sections":["radiation"],"technologies":["imrt-igrt"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-workforce","b-global-access"],"keyPapers":["paper-yang-j-oncol-pract"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A remote-supervision model will maintain IAEA/IROC dosimetry audit pass rates equivalent to on-site physics while reducing the physicist requirement per machine by at least half.","rationale":"Automated QA and log-file analysis already meet or exceed manual checks in accuracy; the constraint is professional custom and regulation rather than physics.","test":"Run a two-year pilot in a network of six machines with two physicists, using independent external dosimetry audits and incident reporting as safety endpoints.","maturity":"early-clinical","actor":"engineering","cost":"medium","horizonYears":3},{"id":"idea-reg-mrct-no-bridging","kind":"idea","name":"One multiregional trial, no bridging studies: enforce ICH E17 in Japan and China","aka":[],"tldr":"Japan and China have often required extra local studies before accepting a global trial. Committing to accept well-designed global trials would bring drugs to Asian patients years earlier.","summary":"ICH E17 (2017) describes how a multiregional clinical trial can support approval in all participating regions. In practice, sponsors still run bridging or local phase 1 studies for Japan and China, and China's requirement for local data has only partly relaxed. The proposal is a formal commitment by PMDA and NMPA, monitored through ICH, that MRCTs meeting E17 criteria (pre-specified regional enrolment, consistency assessment) remove the need for bridging studies, with a published list of exceptions.","asOf":"2026-09-08","links":[{"label":"ICH efficacy guidelines (E17)","url":"https://www.ich.org/page/efficacy-guidelines"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["ncc-japan"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-regulatory-fragmentation","b-trial-diversity"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"The 'drug lag' between US and Japanese or Chinese oncology approvals falls below six months for products developed under E17-compliant MRCTs, compared with a historical lag of two to four years.","rationale":"Ethnic sensitivity for most modern targeted and immune therapies is small and can be assessed within an MRCT; bridging studies delay access without changing decisions in most cases. PMDA's 2024 relaxation of the Japanese phase 1 requirement for many drugs shows movement is possible.","test":"Audit the last 50 oncology approvals in Japan and China for bridging requirements and approval lag; pilot E17 commitments for the next 20 oncology MRCTs with pre-specified regional enrolment.","maturity":"early-clinical","actor":"regulator","cost":"small","horizonYears":3},{"id":"idea-tr1-national-master-trial-agreement","kind":"idea","name":"One national master contract and budget template for all cancer trials","aka":[],"tldr":"Contract negotiation between a hospital and a drug company often takes longer than the trial's first patient. A single pre-agreed contract and budget template, used by everyone, would cut months off opening a trial.","summary":"A government or national research body publishes a non-negotiable model clinical trial agreement (the UK's model agreements and Accelerated Clinical Trial Agreement are precedents) plus a standard per-procedure budget schedule. Sites and sponsors that adopt it skip legal negotiation; adopters are listed publicly and public funders require adoption. Extend the same to a standard data-sharing clause and a standard indemnity.","asOf":"2026-09-08","links":[{"label":"Clinical Trials Transformation Initiative","url":"https://ctti-clinicaltrials.org/"}],"tags":[],"related":["clinicaltrials-gov","eudract-ctis"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["cruk","nci"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-enrolment","b-regulatory-fragmentation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Countries or networks adopting a mandatory model agreement will reduce median site activation time by at least 60 days and increase the number of sites opened per trial.","rationale":"UK sites using the model agreement report shorter set-up; the variance in contracts adds cost without protecting anyone. Standardisation of routine legal instruments has worked in property, finance and open-source licensing.","test":"Compare median site activation time and sites-per-trial in networks before and after mandatory adoption, using registry-recorded activation dates.","maturity":"early-clinical","actor":"policy","cost":"small","horizonYears":2},{"id":"idea-bio1-open-resistance-atlas","kind":"idea","name":"One open atlas of how tumours escape every drug","aka":[],"tldr":"Knowledge about how cancers become resistant is scattered across thousands of papers and company files. Pooling it into one structured, public resource would let anyone see the pattern.","summary":"A curated atlas keyed by drug, target, tumour type and prior therapy, recording observed resistance mechanisms with frequencies, sample sizes and evidence grade, populated from published series, trial correlative data and, ideally, industry-contributed data under a common schema. Analogous resources transformed infectious disease (antimicrobial resistance surveillance) and pharmacogenomics.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Acquired resistance to every therapy): Soria et al., Osimertinib in untreated EGFR-mutated NSCLC (FLAURA, NEJM 2018)","url":"https://doi.org/10.1056/NEJMoa1713137"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["foundation-medicine","guardant-health"],"institutions":[],"pathways":[],"terms":["resistance"],"trials":[],"people":[],"bottlenecks":["b-resistance","b-knowledge-diffusion","b-data-silos"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A structured atlas covering 50 agents reveals that resistance route frequencies are stable enough across cohorts to support pre-specified, mechanism-anticipating combination designs.","rationale":"Individual studies are underpowered to estimate mechanism frequency, which is exactly the number a trial designer needs; harmonised pooling is the only route to it.","test":"Build the atlas for three drug classes with reproducible curation, publish frequency estimates with confidence intervals, and validate them prospectively in an independent progression-biopsy cohort.","maturity":"preclinical-evidence","actor":"data","cost":"small","horizonYears":3},{"id":"idea-data-access-programme-outcomes","kind":"idea","name":"One outcome record for every donated or discounted cancer drug pack","aka":[],"tldr":"Companies and charities give or discount cancer drugs in poorer countries, but nobody records whether the patients did well. Make a simple outcome record part of every programme.","summary":"Access programmes (donations, tiered pricing, patient assistance) treat hundreds of thousands of patients in low- and middle-income countries with no systematic outcome data, so we cannot tell whether treatments developed in high-income trials work under different conditions of nutrition, comorbidity, diagnostics and supportive care. The proposal makes a minimal outcome record (diagnosis, stage, treatment, vital status at 12 months) a condition of participation, captured via mobile registry tools and pooled by a neutral steward.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Weak real-world evidence and registries): Gyawali, Hey & Kesselheim, Assessment of the clinical benefit of cancer drugs receiving accelerated approval (JAMA Intern Med 2019)","url":"https://doi.org/10.1001/jamainternmed.2019.0462"}],"tags":[],"related":["idea-data-registry-in-a-box"],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["real-world-evidence"],"trials":[],"people":[],"bottlenecks":["b-real-world-evidence","b-global-access"],"keyPapers":["paper-gyawali-jama-intern-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Outcome data from access programmes will show that effectiveness in LMIC settings differs substantially from trial results for at least some drugs, changing which drugs and supportive care are prioritised.","rationale":"Paediatric leukaemia programmes in LMICs showed that outcome tracking identified treatment abandonment and toxic death as the main problems, leading to protocol changes that doubled survival.","test":"Add the outcome record to two large access programmes for two years; report completeness and whether the data changed programme design.","maturity":"speculative","actor":"philanthropy","cost":"small","horizonYears":3},{"id":"idea-bio2-rare-cancer-umbrella-platform","kind":"idea","name":"One standing umbrella trial for all rare cancers in a country","aka":[],"tldr":"Rare cancers together make up a fifth of all cancers, but no single one supports its own trial, so most patients get off-label therapy with no data capture. One permanent national umbrella trial, with molecular screening for all comers and arms opened by mechanism, would give every rare cancer a route.","summary":"Rare cancer patients face a structural problem: no single disease supports a trial, so most receive off-label therapy with no data capture. A standing national umbrella (one master protocol, molecular screening for all comers, arms opened by mechanism, shared infrastructure and Bayesian analysis) has precedent in genomically driven platforms and in national molecular screening programmes, but is rarely made permanent or made the default route.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Rare and paediatric cancers without markets): Gatta et al., Rare cancers are not so rare: the rare cancer burden in Europe (EJC 2011)","url":"https://doi.org/10.1016/j.ejca.2011.08.008"}],"tags":[],"related":["clinicaltrials-gov"],"cancers":["sarcoma","neuroendocrine","cholangiocarcinoma"],"sections":[],"technologies":["cgp","ai-trial-matching"],"targets":[],"drugs":[],"companies":["unicancer"],"institutions":["nci","cruk"],"pathways":[],"terms":["basket-umbrella-platform","tumour-agnostic"],"trials":[],"people":[],"bottlenecks":["b-rare-cancers","b-trial-design","b-trial-enrolment"],"keyPapers":["paper-gatta-eur-j-cancer"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A permanent rare cancer umbrella platform enrols over 2,000 patients per year in a mid-sized country, delivers analysable results for at least ten mechanism-defined arms in five years, and reduces the cost per evaluable patient by half.","rationale":"Shared control arms, shared screening and shared infrastructure are the only ways to make small populations statistically and economically tractable, as demonstrated by platform trials in genomic screening programmes and in paediatric oncology consortia.","test":"Fund a three-year platform pilot with pre-specified success metrics on enrolment, arms completed and cost per evaluable patient, compared with the preceding period of standalone rare cancer trials.","maturity":"being-tested-at-scale","actor":"policy","cost":"large","horizonYears":5},{"id":"idea-reg-single-global-dossier","kind":"idea","name":"One structured global dossier: submit the cancer drug file once, to a shared cloud","aka":[],"tldr":"Companies currently reformat the same evidence for every country; a single machine-readable dossier that every regulator reads from would save years of work.","summary":"ICH M4 (the Common Technical Document) harmonised the outline but not the practice: sponsors still produce dozens of regional variants and submit through separate gateways. The proposal is a shared, permissioned cloud repository holding a single eCTD v4 dossier with structured CDISC clinical data, to which any participating regulator is granted read access on the sponsor's instruction, with region-specific content limited to an annex. Regulators would query the same data and share questions.","asOf":"2026-09-08","links":[{"label":"ICH M4 CTD","url":"https://www.ich.org/page/ctd"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["regulatory-agencies"],"trials":[],"people":[],"bottlenecks":["b-regulatory-fragmentation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A single-dossier submission cuts the interval between first and tenth national submission from a median of years to weeks, and reduces sponsor regulatory operations cost per oncology product by at least a third.","rationale":"The gap between first approval and submission in most countries is driven by sponsors sequencing filings by market size, and by the cost of each regional dossier. If the marginal cost of submitting to an extra country is near zero, submissions happen sooner. Aviation and financial regulators already operate shared filing infrastructures.","test":"Have ICH commission a pilot in which three sponsors submit three new oncology products through a shared repository to five regulators simultaneously, measuring reformatting hours and question overlap against matched conventional submissions.","maturity":"speculative","actor":"regulator","cost":"medium","horizonYears":5},{"id":"idea-acc-one-stop-breast-diagnostic-clinic","kind":"idea","name":"One-stop breast clinics: imaging, biopsy and a preliminary answer in a single visit","aka":[],"tldr":"A woman with a breast lump should be examined, scanned and biopsied on the same day, and hear the result within a few days, rather than visiting four times over two months.","summary":"One-stop symptomatic breast clinics with triple assessment on the day have been standard in parts of the UK for decades and cut diagnostic intervals to days. Most health systems still separate imaging, biopsy, and consultation across departments and weeks. Reorganising into a co-located, same-day pathway with rapid pathology is an operational change with a large effect on time to treatment and patient anxiety.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Fragmented care and guideline gaps): Hanna et al., Mortality due to cancer treatment delay: systematic review and meta-analysis (BMJ 2020)","url":"https://doi.org/10.1136/bmj.m4087"}],"tags":[],"related":[],"cancers":["breast-hr-positive","tnbc","breast-her2-positive"],"sections":["diagnostics"],"technologies":["mammography","ultrasound"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-care-fragmentation","b-early-detection"],"keyPapers":["paper-hanna-bmj"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Converting to a one-stop model will reduce median time from referral to definitive diagnosis from more than four weeks to under ten days and reduce the proportion lost before diagnosis by half.","rationale":"Each handoff between departments adds a queue; removing handoffs is the most robust lever on total diagnostic interval.","test":"Before-and-after implementation in five hospitals with diagnostic interval, loss to follow-up, cost per diagnosis, and patient-reported anxiety as endpoints.","maturity":"being-tested-at-scale","actor":"clinic","cost":"medium","horizonYears":2},{"id":"idea-senolytics-after-chemo","kind":"idea","name":"One-two punch: clear senescent cells after chemotherapy","aka":[],"tldr":"Chemotherapy leaves behind senescent cells that inflame tissues and help tumours relapse. A short course of senolytic drugs afterwards might reduce relapse and long-term side effects at once.","summary":"This idea proposes a one-two punch: chemotherapy leaves senescent cells that inflame tissues and help tumours relapse, so a short senolytic course afterwards might cut relapse and late side effects at once. Therapy-induced senescence promotes relapse, cachexia and frailty in models, and senolytics (navitoclax, BCL-XL PROTACs, dasatinib plus quercetin) and uPAR CAR-T clear such cells preclinically (Cellular senescence pathway). The hypothesis is that senolytic consolidation reduces relapse and frailty in patients with a high senescence burden measured by p16, and platelet-sparing BCL-XL degraders remove the toxicity barrier. The test is a randomised phase 2 of such a degrader against placebo after adjuvant chemotherapy in Triple-negative breast cancer (TNBC) or Ovarian cancer.","asOf":"2026-09-08","links":[{"label":"Demaria et al., Cellular senescence promotes adverse effects of chemotherapy and cancer relapse (Cancer Discovery 2017)","url":"https://doi.org/10.1158/2159-8290.CD-16-0241"}],"tags":["mechanism","open-question"],"related":[],"cancers":["tnbc","ovarian"],"sections":["rejuvenation"],"technologies":["protac-degrader","geriatric-assessment"],"targets":["bcl2"],"drugs":[],"companies":[],"institutions":["mskcc","mayo-clinic"],"pathways":["senescence","apoptosis-bcl2"],"terms":["senescent-cells"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-demaria-cancer-discov"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Senolytic consolidation after chemotherapy reduces relapse and treatment-related frailty in patients with high post-treatment senescence burden (p16 expression in blood cells or tumour).","rationale":"Lowe, Demaria, and Kirkland preclinical data; p16INK4a in T cells is a validated senescence biomarker; platelet-sparing BCL-XL degraders remove the main toxicity barrier.","test":"Randomised phase 2 of a platelet-sparing BCL-XL degrader vs placebo after adjuvant chemotherapy in TNBC or ovarian cancer, endpoints DFS and geriatric-assessment frailty scores.","maturity":"preclinical-evidence"},{"id":"idea-tr2-antibody-validation-mandate","kind":"idea","name":"Only use antibodies proven to hit their target with knockout controls","aka":[],"tldr":"A large fraction of commercial research antibodies fail when tested against cells engineered to lack their target, so they do not bind what the label says. Journals and funders should require knockout-validated antibodies for the claims a paper rests on, and fund public validation of the most-used cancer targets.","summary":"Antibody non-specificity is a leading cause of irreproducible results. Initiatives such as YCharOS test commercial antibodies against knockout cell lines and publish the results, finding that a large fraction of antibodies for a given target fail. A requirement that papers cite knockout- or knockdown-validated antibodies (with the validation record) for key claims, and funder support for a public validation programme covering the most-used cancer targets, would remove a pervasive source of error.","asOf":"2026-09-08","links":[{"label":"YCharOS","url":"https://ycharos.com/"}],"tags":[],"related":["hpa","idea-tr2-reagent-lot-ledger"],"cancers":[],"sections":[],"technologies":["histopathology-ihc"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-reproducibility"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Papers using validated antibodies will show higher replication rates than those using unvalidated ones, and the requirement will shift the market towards validated reagents within three years.","rationale":"Independent knockout-based validation is decisive and increasingly cheap; the barrier is that journals do not require it and vendors do not publish it.","test":"Two journals require validation records for key antibodies; measure compliance and downstream replication in a sample of papers.","maturity":"early-clinical","actor":"policy","cost":"small","horizonYears":2},{"id":"idea-data-open-licensed-guidelines","kind":"idea","name":"Open licences for publicly funded cancer guidelines","aka":[],"tldr":"Guidelines paid for with public or charitable money would be published under an open licence so any hospital system, app or country can build them in without permission or fees.","summary":"Guidelines such as NCCN's are copyrighted and licensed commercially, which blocks their embedding in software and their adaptation in low-resource settings. The proposal makes open licensing (CC-BY or similar) a condition of public and charitable funding for guideline development, with a transition fund for bodies that depend on licence income. WHO and some national bodies already publish openly; NCCN and others do not.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Knowledge reaches practice too slowly): Morris, Wooding & Grant, The answer is 17 years, what is the question (JRSM 2011)","url":"https://doi.org/10.1258/jrsm.2011.110180"}],"tags":[],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["nccn","esmo"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-knowledge-diffusion","b-global-access"],"keyPapers":["paper-morris-j-r-soc-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Openly licensed guidelines will be embedded in at least twice as many decision-support and patient-facing products, and adapted in more countries, than comparable restricted guidelines within three years.","rationale":"Open licensing drove the reuse of drug information (e.g., open formularies) and of software; the marginal cost of guideline reuse is near zero, so licensing is the only barrier.","test":"Compare downstream reuse (software integrations, adaptations, translations) of open versus restricted guidelines of similar quality over three years; pilot a transition fund with one guideline body.","maturity":"speculative","actor":"policy","cost":"small","horizonYears":2},{"id":"idea-bio2-fus-for-cell-entry","kind":"idea","name":"Open the barrier so engineered immune cells can enter the brain","aka":[],"tldr":"Engineered immune cells given by drip rarely reach brain tumours. Briefly opening the barrier with focused ultrasound at the right moment may let them in.","summary":"Most focused ultrasound work has aimed at small molecules and antibodies, but preclinical studies show increased trafficking of natural killer cells and CAR-T cells into brain tumours after sonication. Timing matters because the barrier reseals within hours, so the infusion schedule must be matched to the opening window.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The brain: barrier and sanctuary): Stupp et al., Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma (NEJM 2005)","url":"https://doi.org/10.1056/NEJMoa043330"}],"tags":[],"related":[],"cancers":["glioblastoma"],"sections":[],"technologies":["bbb-focused-ultrasound","car-t","glioma-car-t","car-nk-macrophage","immuno-pet"],"targets":["b7h3","gd2"],"drugs":[],"companies":["insightec"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-brain-delivery","b-manufacturing-cell-therapy"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Sonication immediately before or during cell infusion increases intratumoural engineered cell density in the brain by at least fivefold compared with infusion alone, measurable by imaging or by post-mortem and resection tissue analysis.","rationale":"Cell therapy in brain tumours currently requires direct intratumoural or intraventricular delivery, which limits repeat dosing. If systemic infusion could be made to work, cell therapy in the brain would become far more practical.","test":"Large-animal or first-in-human study pairing radiolabelled or reporter-gene-tagged cell infusion with and without sonication, quantifying brain cell delivery as the primary endpoint.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":7},{"id":"idea-data-registry-in-a-box","kind":"idea","name":"Open-source cancer registry-in-a-box for low-resource settings","aka":[],"tldr":"A registry-in-a-box would be a free, ready-to-run cancer registry system, working on phones and without constant internet, so any hospital anywhere can start counting and following its cancer patients.","summary":"Fewer than one in five people in low- and middle-income countries are covered by a high-quality cancer registry. IARC's CanReg5 is the established open tool; the proposal modernises it as a mobile-first, offline-capable system with built-in ICD-O coding assistance, staging, treatment and follow-up modules, automated data-quality checks and export to the Global Initiative for Cancer Registry Development, funded as a global public good with regional support hubs.","asOf":"2026-09-08","links":[{"label":"Global Initiative for Cancer Registry Development (IARC)","url":"https://gicr.iarc.fr/"}],"tags":[],"related":["globocan"],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["iarc"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-data-silos","b-global-access"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Registry-in-a-box deployment will double the number of population-based registries meeting IARC quality criteria in sub-Saharan Africa within seven years.","rationale":"DHIS2 became the health information backbone of more than 70 countries by being free, offline-capable and supported; cancer registration has no equivalent modern tool.","test":"Deploy in ten hospital registries across three countries; measure case completeness and follow-up rates at 24 months against CanReg5 sites.","maturity":"early-clinical","actor":"philanthropy","cost":"medium","horizonYears":4},{"id":"idea-reg-open-source-dossier-tools","kind":"idea","name":"Open-source dossier-building software for academic sponsors and generic makers","aka":[],"tldr":"Preparing a regulatory filing requires expensive specialist software and consultants. Free, open tools would let universities and small generic firms file in more countries.","summary":"Academic groups that run positive trials of repurposed or de-escalated regimens rarely file for label changes because eCTD authoring, publishing and validation tools are commercial and expensive. The proposal is an open-source toolchain (eCTD v4 authoring, CDISC dataset conversion, validation against regional rules, submission gateway clients) maintained by a foundation, plus templated modules for common academic filings such as new-indication supplements for off-patent drugs.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Regulatory divergence between regions): FDA Oncology Center of Excellence, Project Orbis","url":"https://www.fda.gov/about-fda/oncology-center-excellence/project-orbis"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-regulatory-fragmentation","b-generic-repurposing"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Within three years of release, at least ten academic or non-profit sponsors file regulatory submissions using the toolchain that they would otherwise not have made, and the cost of a multi-region generic oncology filing falls by half.","rationale":"Open-source infrastructure has repeatedly lowered barriers where the format is standardised and the buyer base is fragmented (statistics, genomics pipelines). eCTD is a fully specified standard.","test":"Build the minimum toolchain, use it for two real academic new-indication submissions to FDA and EMA, and publish the time and cost against a consultant-led equivalent.","maturity":"speculative","actor":"engineering","cost":"small","horizonYears":3},{"id":"idea-moon-open-source-oncology-drug-discovery","kind":"idea","name":"Open-source drug discovery to clinical proof of concept for neglected cancers","aka":[],"tldr":"For cancers too rare or too poor to attract companies, run drug discovery in the open, the way neglected tropical diseases are tackled, and take candidates to first human trials with public money.","summary":"Paediatric cancers, rare adult cancers and cancers concentrated in low-income countries (Burkitt lymphoma, Kaposi sarcoma, oesophageal squamous cancer in East Africa) receive little industry investment. The Drugs for Neglected Diseases initiative delivered new treatments through open, partnered development. The proposal is an oncology equivalent: open target selection, shared compound libraries, contract chemistry and preclinical development, patent-free or non-exclusive licensing, and public or philanthropic funding through phase 2, with generic manufacturers engaged early.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Rare and paediatric cancers without markets): Gatta et al., Rare cancers are not so rare: the rare cancer burden in Europe (EJC 2011)","url":"https://doi.org/10.1016/j.ejca.2011.08.008"}],"tags":[],"related":[],"cancers":["neuroblastoma","esophageal","sarcoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-rare-cancers","b-funding-allocation","b-ip-collaboration"],"keyPapers":["paper-gatta-eur-j-cancer"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"The initiative delivers at least two candidates to positive phase 2 within eight years for indications with no industry programmes, at a fraction of standard development cost.","rationale":"Where markets fail, product development partnerships have produced approved drugs; oncology has more validated biology to start from than most neglected diseases did.","test":"Fund three programmes (one paediatric, one rare adult, one LMIC-concentrated cancer) with public milestones and open data; success is one investigational new drug filing within four years.","maturity":"speculative","actor":"philanthropy","cost":"large","horizonYears":8},{"id":"idea-prev-open-stage-shift-microsimulation","kind":"idea","name":"Open-source models that translate stage shift into lives saved, for every cancer","aka":[],"tldr":"Whether finding cancer earlier saves lives depends on the cancer. Public models, one per cancer, would let trials and payers predict the mortality benefit from a stage shift honestly.","summary":"CISNET models exist for a few cancers and are not fully open. Propose an open, peer-reviewed microsimulation library covering the 20 commonest cancers, calibrated to registry survival by stage and to the sojourn-time literature, with pre-registration of predicted mortality effects for each MCED trial before readout.","asOf":"2026-09-08","links":[{"label":"CISNET","url":"https://cisnet.cancer.gov"}],"tags":[],"related":[],"cancers":[],"sections":["early-detection"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["stage-shift"],"trials":["nhs-galleri"],"people":[],"bottlenecks":["b-early-detection","b-trial-design"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Pre-registered model predictions fall within the 95% confidence interval of observed mortality effects in at least 70% of subsequent screening trial readouts.","rationale":"Prediction before readout is the only way to test the models and to stop post-hoc rationalisation of stage-shift results.","test":"Fund the library; register predictions for NHS-Galleri and the NCI Vanguard study before their readouts.","maturity":"speculative","actor":"research","cost":"small","horizonYears":3},{"id":"idea-tr1-open-protocol-and-sap-library","kind":"idea","name":"Open-source protocol and statistical analysis plan templates with runnable code","aka":[],"tldr":"Every trial writes its protocol and analysis plan from scratch. A shared library of well-written templates and ready-to-run analysis code would let teams start from the best version rather than a blank page.","summary":"A curated public repository of oncology protocol templates (by design type), statistical analysis plans with executable code (R/Python) for standard endpoints, adaptive designs and estimands, and eligibility criterion libraries with computable definitions. Maintained by cooperative groups and statistical societies with version control and peer review, building on the TransCelerate common protocol template and CDISC standards.","asOf":"2026-09-08","links":[{"label":"TransCelerate BioPharma","url":"https://www.transceleratebiopharmainc.com/"},{"label":"CDISC","url":"https://www.cdisc.org/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["curie-nki-eortc"],"institutions":["nci"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-design","b-knowledge-diffusion","b-reproducibility"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Teams using the library will produce protocols and SAPs in half the time, with fewer regulator queries, and analyses will be more reproducible across trials.","rationale":"Open-source infrastructure accelerated software and genomics; protocol writing remains artisanal. Reuse also propagates good practice (broad eligibility, tolerability estimands) by default.","test":"Release the library and compare protocol development time and query counts for cooperative-group trials that use it versus those that do not over two years.","maturity":"speculative","actor":"research","cost":"small","horizonYears":2},{"id":"idea-data-open-line-of-therapy-algorithms","kind":"idea","name":"Open, benchmarked algorithms for lines of therapy and progression from routine data","aka":[],"tldr":"Publish the exact rules used to work out from messy hospital records which treatment a patient was on and when it stopped working, and test them all on the same data.","summary":"Real-world studies depend on deriving line of therapy, progression and response from records, but every vendor and academic group uses proprietary rules, so results are not comparable. The proposal is an open library of versioned derivation algorithms with a benchmark dataset of chart-reviewed cases, run as a public leaderboard, so studies can cite algorithm version and known error rates.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Data silos): AACR Project GENIE","url":"https://www.aacr.org/professionals/research/aacr-project-genie/"}],"tags":[],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["real-world-evidence","pfs"],"trials":[],"people":[],"bottlenecks":["b-data-silos","b-real-world-evidence"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Open benchmarked algorithms will reduce between-study variation in real-world PFS estimates for the same cohort by half and become the reference method in regulatory RWE submissions.","rationale":"In genomics, open benchmarked pipelines (GATK, Genome in a Bottle) made variant calling comparable across labs; RWE has no equivalent for its core derived variables.","test":"Assemble 2,000 chart-reviewed patients across three cancers as a benchmark; invite groups to submit algorithms; publish accuracy and inter-algorithm agreement.","maturity":"early-clinical","actor":"research","cost":"small","horizonYears":2},{"id":"idea-organ-preservation-esophageal","kind":"idea","name":"Organ preservation as the default after complete response in oesophageal cancer","aka":[],"tldr":"Oesophagectomy is one of the hardest operations in surgery. If chemoradiation (with or without immunotherapy) has made the tumour disappear, skip it and watch.","summary":"SANO showed non-inferior 2-year survival for active surveillance in clinical complete responders after CROSS. Adding PD-1 blockade to chemoradiation (KEYNOTE-975, SKYSCRAPER-07, ESCORT-CRT) may raise complete response rates and make surveillance viable for more patients; ctDNA and PET could sharpen response assessment.","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT05953181: SANO","url":"https://clinicaltrials.gov/study/NCT05953181"}],"tags":[],"related":[],"cancers":["esophageal"],"sections":[],"technologies":["active-surveillance","imrt-igrt","checkpoint-inhibitor","mrd-testing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["clinical-complete-response"],"trials":["sano","cross"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Definitive chemoradiation + PD-1 blockade followed by ctDNA- and endoscopy-guided surveillance, with salvage surgery on regrowth, yields non-inferior 3-year OS to planned oesophagectomy in squamous cell carcinoma.","rationale":"ESCC is highly radiosensitive and immunotherapy-responsive; salvage surgery after regrowth was feasible in SANO.","test":"Randomised non-inferiority trial in ESCC with cCR after chemoradiation-IO; OS primary, oesophagectomy-free survival and quality of life secondary.","maturity":"being-tested-at-scale"},{"id":"idea-fund-pay-for-cure-annuities","kind":"idea","name":"Outcome-based annuity payments for potentially curative one-time therapies","aka":[],"tldr":"Instead of paying hundreds of thousands up front for a CAR-T or gene therapy, the health system would pay in yearly instalments that stop if the cancer comes back, so companies are paid for cures, not attempts.","summary":"Outcome-based annuities, already used for some gene therapies (for example spinal muscular atrophy and haemophilia contracts in Europe), applied systematically to cell therapies, bispecifics with curative potential and future one-time oncology treatments: payment spread over five years, each instalment contingent on the patient remaining in remission by pre-agreed criteria (imaging, MRD negativity). Payers gain risk-sharing; manufacturers gain higher total payment for real cures and a strong incentive to select patients well and improve durability. Needs a registry to adjudicate outcomes and accounting rules that let payers commit across years.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Incentives reward me-too drugs and marginal gains): Upadhaya et al., PD1/PDL1 inhibitor clinical trial landscape (Nat Rev Drug Discov 2022)","url":"https://doi.org/10.1038/d41573-022-00030-4"}],"tags":[],"related":["idea-fund-public-car-t-manufacturing","idea-fund-mcbs-linked-pricing"],"cancers":["dlbcl","multiple-myeloma"],"sections":[],"technologies":["car-t","mrd-testing"],"targets":[],"drugs":["axicabtagene-ciloleucel","ciltacabtagene-autoleucel"],"companies":[],"institutions":[],"pathways":[],"terms":["mrd","real-world-evidence"],"trials":[],"people":[],"bottlenecks":["b-incentive-misalignment","b-drug-pricing"],"keyPapers":["paper-upadhaya-nat-rev-drug-discov"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Annuity contracts for CAR-T in lymphoma and myeloma lower payer cost per durable remission by at least 20% compared with up-front pricing, without reducing patient access, and manufacturers increase investment in durability (consolidation, MRD-guided retreatment) measurably.","rationale":"Contracts exist for Zolgensma and haemophilia gene therapies in several countries; oncology has cleaner outcome definitions (relapse) than many indications. Paying for outcomes corrects the current system where a therapy that fails at month six costs the same as one that cures.","test":"A national payer pilots annuity contracts for CAR-T in one indication with a registry-based remission adjudication, comparing cost per remission-year and access metrics against a control region with up-front pricing.","maturity":"early-clinical","actor":"payer","cost":"medium","horizonYears":4},{"id":"idea-tr1-paid-community-advisory-boards","kind":"idea","name":"Paid community advisory boards with power to change protocol burden","aka":[],"tldr":"Before a trial is finalised, a paid panel of patients and community members from the groups the trial needs would review it and could require changes to visit schedules, procedures and materials that would deter people like them.","summary":"Sponsors convene standing, compensated community advisory boards representative of the target population for each disease programme; boards review protocols for burden (visits, biopsies, travel, language), consent materials and recruitment plans, and their recommendations must be adopted or publicly answered. Precedent from HIV research networks, where community boards are structural.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Trials do not represent the people who get cancer): Loree et al., Disparity of race reporting and representation in trials leading to cancer drug approvals (JAMA Oncology 2019)","url":"https://doi.org/10.1001/jamaoncol.2019.1870"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["nci"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-diversity","b-patient-voice"],"keyPapers":["paper-loree-jama-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Protocols reviewed by empowered community boards will have fewer research-only procedures, more flexible visit windows and higher enrolment and retention of the target groups than unreviewed protocols.","rationale":"HIV trial networks with community advisory boards achieved higher minority participation than oncology; burden is a leading reason for refusal, and those affected can identify it early.","test":"Within one sponsor, assign half of new protocols to board review; compare procedure counts, enrolment demographics and retention.","maturity":"early-clinical","actor":"industry","cost":"small","horizonYears":1},{"id":"idea-tr2-paid-statistical-review","kind":"idea","name":"Paid independent statistical review for preclinical papers that inform trials","aka":[],"tldr":"Clinical trials get expert statistical review; the laboratory studies that justify them usually do not. Paying statisticians to review these papers before they influence a trial would catch errors early.","summary":"Statistical errors in preclinical papers (pseudo-replication, inappropriate tests, no correction for multiple comparisons) are common and are rarely caught by biologist reviewers. Journals could not afford it; a funder-supported service that provides paid statistical review for preclinical papers cited in trial protocols or investigational new drug packages, with a published statistical report, would target the small fraction of papers that matter most for translation.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Preclinical results do not reproduce): Errington et al., Investigating the replicability of preclinical cancer biology (eLife 2021)","url":"https://doi.org/10.7554/eLife.71601"}],"tags":[],"related":["idea-tr2-automated-stats-check","idea-tr2-replication-before-ind"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-reproducibility","b-translational-valley"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Statistical review will identify errors changing the interpretation in at least 20% of translationally important preclinical papers, and trials informed by reviewed papers will have lower early futility rates.","rationale":"Statistical review is standard in clinical journals and reduces error; its absence in preclinical publishing is an economic rather than a scientific choice.","test":"Review 200 preclinical papers cited in registered trial protocols; publish the error rate and types; follow the trials.","maturity":"speculative","actor":"philanthropy","cost":"medium","horizonYears":2},{"id":"idea-moon-peer-navigator-workforce","kind":"idea","name":"Paid survivor peer-navigators as a recognised health workforce role","aka":[],"tldr":"Train and pay people who have been through cancer to guide newly diagnosed patients through the system, especially where oncologists and nurses are scarce.","summary":"Community health workers transformed HIV and maternal care delivery in low-resource settings. Cancer has peer support but rarely a paid, trained, supervised navigator role. The proposal is a certified curriculum (system navigation, plain explanation of treatment, side-effect triage, financial and legal signposting, misinformation response), a salaried role in cancer units and community clinics, and a supervision structure under nursing.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Patients lack understanding, navigation and agency): Basch et al., Overall survival results of a trial assessing patient-reported outcomes for symptom monitoring during routine cancer treatment (JAMA 2017)","url":"https://doi.org/10.1001/jama.2017.7156"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["tata-memorial"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-patient-voice","b-workforce","b-global-access"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Peer navigators reduce treatment abandonment (a major cause of death in low- and middle-income settings, especially in childhood cancer) by a third and increase completion of radiotherapy and chemotherapy courses.","rationale":"Abandonment is driven by cost, distance, confusion and fear, all of which peers address more credibly than clinicians. The workforce constraint is on scarce clinicians, not on trainable survivors.","test":"Cluster-randomised trial in cancer units in two middle-income countries; primary endpoint treatment completion, secondary time to treatment and patient-reported understanding.","maturity":"early-clinical","actor":"policy","cost":"medium","horizonYears":3},{"id":"idea-moon-palliative-care-from-diagnosis-everywhere","kind":"idea","name":"Palliative care from diagnosis for every advanced cancer, including opioid access, worldwide","aka":[],"tldr":"Palliative care given early alongside cancer treatment improves quality of life and sometimes survival, and most of the world has no access to it or to morphine. Make both universal.","summary":"Early integrated palliative care improved quality of life, mood and in some trials survival in metastatic cancer (Temel 2010), and is guideline-recommended, yet is delivered late or not at all in most settings; the Lancet Commission on palliative care documented that most of the world's population lacks access to opioids for pain. The proposal is a global standard: automatic palliative care referral at diagnosis of advanced cancer, trained generalist palliative capacity in every cancer unit, and a financed programme guaranteeing affordable oral morphine and essential palliative medicines in every country.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Pain relief and palliative care are unavailable to most): WHO fact sheet, Palliative care","url":"https://www.who.int/news-room/fact-sheets/detail/palliative-care"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["mgh"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-palliative","b-global-access"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Universal early palliative care and opioid access reduce severe uncontrolled pain at end of life by over half and improve quality of life scores in advanced cancer across participating countries.","rationale":"The evidence is settled and the interventions are inexpensive; the barriers are regulation of opioids, workforce and the misconception that palliative care means giving up.","test":"National implementation in three countries with a WHO-style essential package; measure opioid availability, referral timing and patient- and family-reported outcomes against matched countries.","maturity":"being-tested-at-scale","actor":"policy","cost":"large","horizonYears":5},{"id":"idea-pdac-enzyme-replacement-prescribing-by-default","kind":"idea","name":"Pancreatic enzyme replacement by default: prescribe at diagnosis, audit the rate, and run the trial that settles survival","aka":[],"tldr":"The pancreas makes the enzymes that digest food, and a cancer in it, or the operation to remove it, leaves most patients unable to absorb what they eat. Capsules replacing those enzymes are cheap and recommended, yet UK records show only one patient in five was prescribed them. The proposal is to prescribe by default at diagnosis, publish each hospital's rate, and run the trial never done.","summary":"Traverso and Longmire recorded in 1980 that every one of their 18 pylorus-preserving patients had marked pancreatic insufficiency and needed intensive enzyme replacement. Roberts 2019, in 4,554 UK primary care patients with pancreatic adenocarcinoma, found enzyme replacement prescribed to 21.7 percent, and in 807 propensity-matched pairs an adjusted survival time ratio of 2.62 (95 percent confidence interval 2.27 to 3.02), consistent across surgery and chemotherapy subgroups. NICE NG85 (2018) recommends enteric-coated pancreatin for unresectable disease and after resection, and the National Pancreatic Cancer Audit now reports prescribing as a performance indicator in England (the Wales data item was unavailable in the first report). The proposal has three parts: an opt-out prescription at diagnosis in every pancreatic multidisciplinary team, with dose titration by a dietitian; publication of the audit indicator by trust; and a pragmatic randomised or stepped-wedge trial of default prescribing against usual care with survival, weight and chemotherapy delivery as outcomes, since the survival association is observational and confounded by fitness. The UK figures and the audit's recommendations are on the UK and NHS page.","asOf":"2026-09-24","links":[{"label":"Roberts et al.: enzyme replacement and survival in pancreatic cancer (Pancreatology 2019)","url":"https://europepmc.org/article/MED/30385188"},{"label":"NICE NG85: pancreatic cancer in adults (2018)","url":"https://www.nice.org.uk/guidance/ng85"},{"label":"National Pancreatic Cancer Audit reports (NATCAN)","url":"https://www.natcan.org.uk/reports/?audit=pancreatic"}],"tags":["pancreatic-evidence"],"related":["idea-pdac-cachexia-trials-embedded-in-chemotherapy-trials","idea-pdac-uk-active-treatment-rate-audit-and-target"],"cancers":["pancreatic"],"sections":["supportive-care","nutrition-lifestyle"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["whipple"],"trials":[],"people":[],"bottlenecks":["b-cachexia-supportive","b-knowledge-diffusion","b-care-fragmentation"],"keyPapers":["paper-roberts-pert-survival-pancreatic-cancer-pancreatology-2019","paper-traverso-longmire-pylorus-preservation-pancreaticoduodenectomy-sgo-1978"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Default enzyme replacement at diagnosis raises the prescribing rate above 80 percent, and in a pragmatic randomised comparison against usual care improves weight maintenance and chemotherapy delivery, with a survival gain that is smaller than the observational estimate but real.","rationale":"The intervention is cheap, guideline-endorsed and safe; the gap is behavioural and organisational; the observational survival signal is large enough to warrant a trial and too confounded to act on alone.","test":"Stepped-wedge or cluster randomised trial of opt-out prescribing across pancreatic multidisciplinary teams, with the audit indicator as the process measure and weight, relative dose intensity and overall survival as outcomes.","maturity":"early-clinical","actor":"clinic","cost":"small","horizonYears":3},{"id":"idea-tr1-parallel-comorbidity-cohorts","kind":"idea","name":"Parallel real-world cohorts for sicker patients alongside every pivotal trial","aka":[],"tldr":"Instead of excluding sicker patients entirely, trials would run a side group for them, receiving the new drug with closer monitoring, so we learn how it behaves in the people who will actually get it.","summary":"Registrational trials open a non-randomised parallel cohort for patients who fail the main eligibility on performance status (ECOG 2), organ function, or comorbidity, treated with the experimental regimen under a pre-specified safety and dose-adjustment plan, with PK sampling. Data are analysed separately and included in the label as descriptive evidence. Precedent: NCI organ-dysfunction working group studies and some sponsor expansion cohorts.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Trials do not represent the people who get cancer): Loree et al., Disparity of race reporting and representation in trials leading to cancer drug approvals (JAMA Oncology 2019)","url":"https://doi.org/10.1001/jamaoncol.2019.1870"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["geriatric-assessment"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-diversity","b-aging-comorbidity"],"keyPapers":["paper-loree-jama-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Parallel cohorts will generate dosing and safety guidance for ECOG 2 and organ-impaired patients at approval in most programmes, and real-world toxicity in those groups will fall as clinicians use it.","rationale":"ECOG 2 patients are a substantial share of real-world recipients and are almost absent from trials; clinicians extrapolate from fitter patients with predictable harm.","test":"Sponsors open parallel cohorts in ten registrational trials; measure enrolment feasibility, the fraction generating label text, and subsequent real-world outcomes in the affected groups.","maturity":"early-clinical","actor":"industry","cost":"medium","horizonYears":3},{"id":"idea-fund-neglected-cancer-lottery","kind":"idea","name":"Partial lottery funding for good proposals in under-funded cancers","aka":[],"tldr":"Once a proposal in a neglected cancer passes a quality bar, pick winners by lottery instead of by tiny differences in review scores, which mostly reflect fashion.","summary":"Reviewer scores in the middle of the distribution are nearly random and are known to favour established fields and safe applicants. For pancreatic, oesophageal, glioblastoma, sarcoma, mesothelioma and other neglected cancers, a funder would run a two-stage process: a rigorous pass/fail quality gate, then random selection among passes. This removes fashion bias, lowers the cost of applying and reviewing, and makes it easier to enter a new field.","asOf":"2026-09-08","links":[{"label":"Health Research Council of New Zealand","url":"https://www.hrc.govt.nz/"}],"tags":[],"related":["idea-fund-fast-grants-oncology"],"cancers":["pancreatic","esophageal","glioblastoma","sarcoma","mesothelioma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-funding-allocation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Lottery-selected awards in neglected cancers produce outputs (papers, replications, follow-on funding, trials started) at least equal to score-ranked awards, while attracting a broader pool of applicants, more first-time entrants to the field and shorter proposals.","rationale":"The Swiss National Science Foundation, the Health Research Council of New Zealand and the Volkswagen Foundation have used partial lotteries with no measurable loss of quality; the Health Research Council found applicant time and reviewer load fell. Modified lotteries are now recommended by several meta-research groups.","test":"Randomised funder experiment: among proposals passing the gate, half are funded by score rank and half by lottery, then compare five-year outputs and applicant diversity.","maturity":"speculative","actor":"philanthropy","cost":"medium","horizonYears":3},{"id":"idea-cost-340b-pass-through","kind":"idea","name":"Pass 340B discounts on cancer drugs through to the patient's bill","aka":[],"tldr":"Hospitals in the 340B programme buy cancer drugs at steep discounts but usually bill patients and insurers the full price; requiring the discount to reach low-income patients would turn a hospital subsidy into patient relief.","summary":"The 340B programme lets qualifying hospitals buy outpatient drugs at discounts of 25% to 50% or more, with no requirement that the saving reach the patient. HRSA reported $66.3 billion of purchases at 340B prices in 2023. A pass-through rule would require covered entities to charge uninsured and under-insured patients no more than the 340B acquisition cost plus a dispensing fee for oncology drugs, with the hospital keeping the margin only on insured patients.","asOf":"2026-09-10","links":[{"label":"HRSA: 340B Drug Pricing Program","url":"https://www.hrsa.gov/opa"},{"label":"GAO-15-442: Medicare Part B drugs and 340B hospitals (2015)","url":"https://www.gao.gov/products/gao-15-442"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["340b-program","financial-toxicity"],"trials":[],"people":[],"bottlenecks":["b-drug-pricing","b-incentive-misalignment"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A pass-through requirement for uninsured and under-insured patients will reduce out-of-pocket oncology drug bills at 340B hospitals by more than half for those patients without reducing hospital participation in the programme.","rationale":"The programme's statutory purpose is to stretch scarce resources for vulnerable patients; the mechanism exists (some hospitals already do this voluntarily) but is not required.","test":"State-level pass-through laws in two or three states, evaluated against neighbouring states on patient charges, charity care and hospital participation.","maturity":"speculative","actor":"policy","cost":"medium","horizonYears":3},{"id":"idea-fund-value-based-patent-extension","kind":"idea","name":"Patent term extension scaled to proven survival gain","aka":[],"tldr":"A drug that adds years of life would earn extra years of market protection; one that adds a few weeks would earn none. Extensions would be lost if the promised benefit is not confirmed.","summary":"Supplementary protection or regulatory exclusivity would be granted in proportion to demonstrated overall survival or cure-rate gain over the best prior standard in a randomised trial (for example one additional year of exclusivity per six months of median overall survival gain, capped at five years, with bonuses for curative-intent settings). Approvals on surrogate endpoints receive provisional extension that is confirmed or revoked when survival data mature. Regulators already collect the necessary data; the change is to the reward, not the evidence standard.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Incentives reward me-too drugs and marginal gains): Upadhaya et al., PD1/PDL1 inhibitor clinical trial landscape (Nat Rev Drug Discov 2022)","url":"https://doi.org/10.1038/d41573-022-00030-4"}],"tags":[],"related":["idea-fund-benefit-indexed-exclusivity","idea-fund-cure-prize"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["os","pfs","accelerated-approval"],"trials":[],"people":[],"bottlenecks":["b-incentive-misalignment","b-trial-design"],"keyPapers":["paper-upadhaya-nat-rev-drug-discov"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Linking exclusivity to survival gain shifts industry portfolios: within a decade the share of pivotal trials with overall survival as a primary or co-primary endpoint rises substantially, and the average survival gain of approved drugs increases relative to the prior decade.","rationale":"Exclusivity is the main lever of pharmaceutical reward and is currently flat with respect to benefit; paediatric exclusivity extensions show that firms respond strongly to even six months of added protection. Value-based rewards are the explicit goal of ESMO-MCBS and ASCO value frameworks, which are advisory today.","test":"Use economic modelling with historical approvals to calibrate the schedule, then run a legislated pilot in one jurisdiction for new oncology approvals over five years, tracking endpoint choice and benefit magnitude of filings.","maturity":"speculative","actor":"policy","cost":"small","horizonYears":6},{"id":"idea-fund-open-source-repurposing-leads","kind":"idea","name":"Patent-free open-source development of repurposed and off-patent cancer drugs","aka":[],"tldr":"Fund trials of old, cheap drugs with anti-cancer signals without seeking patents, and have generic makers produce them, so cost, not profit, decides whether patients get them.","summary":"A philanthropic programme (building on the Anticancer Fund, Cures Within Reach and the Repurposing Drugs in Oncology project) selects repurposing candidates by strength of signal (for example propranolol in angiosarcoma, metformin in specific molecular subgroups, mebendazole, statins in defined contexts), funds definitive randomised trials through academic networks, and commits in advance to open, patent-free results with pre-agreed generic supply. Label changes are pursued through regulatory pathways that allow non-commercial sponsors, or through guideline inclusion where labelling is impractical. Pairing with the non-profit pharma and indication-exclusivity ideas makes the economics self-sustaining.","asOf":"2026-09-08","links":[{"label":"Anticancer Fund","url":"https://www.anticancerfund.org/"},{"label":"Cures Within Reach","url":"https://www.cureswithinreach.org/"}],"tags":[],"related":["idea-fund-repurposing-indication-exclusivity","idea-fund-nonprofit-pharma"],"cancers":["sarcoma","colorectal","prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-incentive-misalignment","b-generic-repurposing"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"An open repurposing programme funded at $30 million a year delivers at least three guideline-changing randomised results within seven years at under $10 million per trial, and the resulting treatments are available at generic prices in all participating countries within two years of publication.","rationale":"STAMPEDE showed that adding cheap generics (abiraterone was not generic then, but docetaxel and later celecoxib arms were) to standard care in a platform can change practice; the Add-Aspirin trial and the Anticancer Fund's portfolio demonstrate the pipeline exists. The barrier is sponsorship and a path to label, not science.","test":"Fund two randomised trials with committed generic supply and pre-registered guideline-inclusion plans; evaluate accrual, cost and guideline uptake at five years.","maturity":"early-clinical","actor":"philanthropy","cost":"medium","horizonYears":5},{"id":"idea-acc-pathologist-assistants-and-ai-triage","kind":"idea","name":"Pathologist assistants plus AI triage to multiply pathologist capacity","aka":[],"tldr":"Much of a pathologist's day is preparation, measuring and describing specimens. Trained assistants can do that, and AI can pre-screen slides, so each pathologist reports far more cancers.","summary":"Pathologists' assistants (a recognised profession in North America) perform gross examination and dissection, while AI tools can pre-screen slides for likely malignancy and prioritise them. Together these could double the throughput of a pathologist without lowering quality. Most health systems have neither role nor tool in routine use. The proposal is a combined workforce-and-technology package with a training route for assistants and validated AI triage.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Not enough oncologists, nurses, pathologists, physicists): Yang et al., Projected supply of and demand for oncologists and radiation oncologists through 2025 (JOP 2014)","url":"https://doi.org/10.1200/JOP.2013.001319"}],"tags":[],"related":["idea-acc-ai-first-pathology-common-cases"],"cancers":[],"sections":["diagnostics"],"technologies":["digital-pathology-ai"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-workforce","b-ai-validation"],"keyPapers":["paper-yang-j-oncol-pract"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Laboratories deploying assistants and AI triage will increase cancers reported per pathologist-hour by at least 80% and reduce median turnaround time by a third, with no increase in major discrepancies on audit.","rationale":"Grossing and screening are the time-consuming, protocol-driven parts of pathology; AI triage has shown high sensitivity in prostate and lymph node screening tasks.","test":"A controlled implementation in four laboratories with time-motion, turnaround, and discrepancy-rate measurement against matched laboratories.","maturity":"early-clinical","actor":"clinic","cost":"medium","horizonYears":3},{"id":"idea-acc-reflex-genomic-profiling-at-diagnosis","kind":"idea","name":"Pathologists order genomic profiling automatically at diagnosis of advanced cancer","aka":[],"tldr":"A substantial share of patients with advanced non-small-cell lung cancer start first-line treatment before their biomarker results arrive, or without full testing, and so miss targeted therapy. Letting the pathologist order the full genomic panel the moment a cancer of a defined type and stage is confirmed shortens time to result and makes testing complete.","summary":"Real-world data show that a substantial fraction of patients with advanced NSCLC begin first-line therapy before biomarker results are available or without full testing, forgoing targeted therapy. Reflex testing, ordered by the pathologist at diagnosis on defined tumour types and stages, shortens time to result and increases completeness. Tissue stewardship, funding, and a default panel need agreement. Some regions have adopted reflex testing; most have not.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Fragmented care and guideline gaps): Hanna et al., Mortality due to cancer treatment delay: systematic review and meta-analysis (BMJ 2020)","url":"https://doi.org/10.1136/bmj.m4087"}],"tags":[],"related":[],"cancers":["nsclc","colorectal"],"sections":[],"technologies":["cgp","companion-diagnostic"],"targets":[],"drugs":["foundationone-cdx"],"companies":[],"institutions":[],"pathways":[],"terms":["first-line","ngs"],"trials":[],"people":[],"bottlenecks":["b-care-fragmentation","b-biomarker-validation"],"keyPapers":["paper-hanna-bmj"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Reflex comprehensive profiling will increase the proportion of advanced NSCLC and colorectal cancer patients with complete guideline biomarker results before first-line treatment from under 60% to above 90%, and increase targeted-therapy use in eligible patients.","rationale":"Reflex HER2 and ER testing in breast cancer is universal and uncontroversial; extending the same logic to genomic panels removes an avoidable coordination failure.","test":"A regional switch to reflex ordering with pre-post measurement of completeness, turnaround, targeted-therapy uptake, and tissue-exhaustion rates.","maturity":"being-tested-at-scale","actor":"clinic","cost":"medium","horizonYears":2},{"id":"idea-moon-navigation-as-a-right","kind":"idea","name":"Patient navigation as a legal entitlement from the day of diagnosis","aka":[],"tldr":"Every person told they have cancer gets a named navigator, by law, who helps them understand options, book appointments, find trials and deal with money and work.","summary":"Navigation programmes (Harold Freeman model, Harlem) cut time-to-treatment and improve completion of therapy, and US Medicare began paying for Principal Illness Navigation in 2024. The proposal is to make navigation a statutory entitlement in every health system, funded per diagnosis, with a minimum service specification (first contact within 72 hours, written summary after each key consultation, a trial-eligibility check at each decision point) and public reporting of coverage.","asOf":"2026-09-08","links":[{"label":"Harold P. Freeman Patient Navigation Institute","url":"https://www.hpfreemanpni.org/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-patient-voice","b-care-fragmentation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Universal funded navigation reduces time from diagnosis to first treatment by at least 20% and raises trial enrolment and guideline-concordant care, with the largest gains in deprived and rural populations.","rationale":"Fragmented care is the norm and the patients who fall through gaps are the ones with the least literacy and time. Navigation is one of the few interventions with consistent effects on timeliness and equity, and lay navigators are cheap relative to oncology drugs.","test":"Stepped-wedge rollout across one region or national payer: compare diagnosis-to-treatment interval, emergency admissions, trial enrolment and patient-reported understanding before and after entitlement; cost per quality-adjusted life-year against standard care.","maturity":"being-tested-at-scale","actor":"policy","cost":"medium","horizonYears":3},{"id":"idea-moon-patient-designed-trials","kind":"idea","name":"Patient panels approve trial burden and endpoints as a condition of funding","aka":[],"tldr":"Before a trial is funded, patients who have had the disease sign off on how many visits, scans and blood draws it demands, and on whether the endpoints measure things that matter to them.","summary":"Trial protocols are written by sponsors and statisticians; visit burden, exclusion criteria and endpoints reflect regulatory habit rather than what participants can tolerate or value. Funders (public and charitable) would require a structured patient review of burden, eligibility and endpoints, with a published response to each recommendation, before release of funds. PCORI and some UK funders already require patient involvement; this makes it a gate with teeth and a measurable output.","asOf":"2026-09-08","links":[{"label":"PCORI","url":"https://www.pcori.org/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-patient-voice","b-trial-design"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Patient-gated protocols recruit faster and retain more participants (dropout down by a quarter) and include at least one patient-prioritised endpoint in over 80% of cases.","rationale":"Feasibility failures are the commonest reason trials close early. Patients are the best judges of what they will actually do for two years.","test":"Funder adopts the gate for half of its calls at random; compare accrual rate, dropout and endpoint composition between gated and ungated trials over three years.","maturity":"early-clinical","actor":"philanthropy","cost":"small","horizonYears":3},{"id":"idea-organoid-guided-adc","kind":"idea","name":"Patient-derived organoids to pick ADC payloads","aka":[],"tldr":"Grow the patient's tumour in a dish and test which ADC payload kills it before choosing among three TROP2 ADCs.","summary":"Grow the patient's tumour in a dish and test which ADC payload kills it before choosing among the TROP2 ADCs. Payload sensitivity to SN-38, DXd or MMAE varies by tumour and is not predicted by antigen level, while organoids retain drug sensitivity profiles and can be tested with free payloads within two to three weeks. Functional testing already correlates with response in colorectal and pancreatic cancer, and payload effect dominates ADC efficacy once delivery is adequate. The test is a prospective observational study in metastatic TNBC starting a TROP2 ADC, comparing organoid payload IC50 with RECIST response and PFS. With preclinical evidence, it addresses the bottlenecks Lab models that fail to predict what happens in patients and Too many combinations to test.","asOf":"2026-09-04","links":[],"tags":[],"related":[],"cancers":["tnbc","breast-hr-positive"],"sections":[],"technologies":["organoids","functional-drug-testing","adc"],"targets":[],"drugs":["sacituzumab-govitecan","datopotamab-deruxtecan"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Ex vivo payload sensitivity of organoids predicts clinical response to the corresponding ADC.","rationale":"Functional testing correlates with response in colorectal and pancreatic cancer; payload effect dominates ADC efficacy once delivery is adequate.","test":"Prospective observational study in metastatic TNBC starting a TROP2 ADC: organoid payload IC50 vs RECIST response and PFS.","maturity":"preclinical-evidence"},{"id":"idea-fund-portable-patient-consent","kind":"idea","name":"Patient-held portable consent for reusing samples and data across studies","aka":[],"tldr":"Patients would carry a digital consent that says how their trial samples and records may be reused, so their contribution is not locked to one company or study and they decide who benefits from it.","summary":"A patient-controlled dynamic consent record, interoperable across trial sponsors and health systems, in which patients specify permitted secondary uses (academic research, commercial research, specific diseases, return of results) and can update choices. Sponsors adopt the record in trial consent, and the data and biospecimen commons honour it. This shifts the legal basis for reuse from sponsor-controlled contracts to patient authorisation, unblocking most of the reuse that current bilateral contracts prevent, and gives patient groups negotiating power over how their collective contribution is used. Count Me In, the Metastatic Breast Cancer Project and the UK's Our Future Health show patients consent broadly when asked directly.","asOf":"2026-09-08","links":[{"label":"Count Me In","url":"https://joincountmein.org/"}],"tags":[],"related":["idea-fund-trial-biospecimen-commons","idea-fund-trial-data-trust","idea-fund-patient-burden-review-criterion"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-ip-collaboration","b-patient-voice","b-data-silos"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Where portable consent is offered, more than 80% of trial participants authorise broad research reuse, and secondary use of their samples and data (studies approved) is at least twice that of participants under conventional sponsor-specific consent.","rationale":"Direct-to-patient research projects consistently show high willingness to share broadly; the barrier to reuse is contractual and institutional, and consent that travels with the patient removes the sponsor as gatekeeper. Dynamic consent platforms have been piloted in genomics programmes.","test":"Deploy portable consent in three trials across two sponsors; measure authorisation rates, subsequent approved reuse and participant satisfaction against matched conventional trials.","maturity":"early-clinical","actor":"patients","cost":"medium","horizonYears":3},{"id":"idea-tr2-failed-trial-ipd-default","kind":"idea","name":"Patient-level data from failed trials becomes open by default after two years","aka":[],"tldr":"When a trial fails, the company has little commercial reason to keep the detailed data secret. Make sharing it the default rather than something researchers must beg for.","summary":"Platforms such as Vivli and YODA share individual participant data on request, but sponsors control access and failed trials are under-represented. Since a discontinued programme has little competitive value, a policy (via funders, journals and regulators) that participant-level data from terminated oncology programmes is deposited with open access after 24 months would unlock meta-analysis, biomarker work and methods research.","asOf":"2026-09-08","links":[{"label":"Vivli","url":"https://vivli.org/"},{"label":"YODA Project","url":"https://yoda.yale.edu/"}],"tags":[],"related":["idea-tr2-failed-trial-biobank"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-negative-results","b-data-silos"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Within three years, participant-level data from at least half of terminated phase 2 and 3 oncology programmes is available for download or streamlined access, up from a small minority today.","rationale":"Trial participants consented to advance knowledge; data locked after failure honours neither them nor the science. Trials with shared data generate multiple secondary publications.","test":"Adopt the policy at two major funders and one journal group; measure deposit rates and secondary analyses.","maturity":"early-clinical","actor":"policy","cost":"small","horizonYears":2},{"id":"idea-multimodal-foundation-model","kind":"idea","name":"Patient-level multimodal foundation models for treatment selection","aka":[],"tldr":"Train one AI on scans, pathology slides, genomics and treatment outcomes pooled across patients, including completed phase 3 trials, so it can predict which treatment will work for a new patient. Pathology and radiology models already exist separately; combining them with genomic and trial outcome data is the untested step.","summary":"Train one AI on scans, slides, genomics and outcomes pooled across patients, including completed phase 3 trials, so that it can predict, for a new patient, which treatment will work. Pathology and radiology foundation models exist separately; combining them with genomic and clinical data, as Tempus AI, Owkin and CanSim-style efforts are doing, is the next step, and ArteraAI showed that single-modality models can be predictive. Adding outcomes from randomised trials would allow causal treatment-effect estimation, for example TROP2 ADC versus chemotherapy. The test is to train on completed phase 3 datasets with sponsors, validate on held-out trials and then run a prospective biomarker-stratified trial. With preclinical evidence, it addresses the bottlenecks Data silos and AI that is built but not validated or deployed.","asOf":"2026-09-04","links":[{"label":"Chen et al., Towards a general-purpose foundation model for computational pathology (Nature Medicine 2024)","url":"https://doi.org/10.1038/s41591-024-02857-3"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["pathology-foundation-model","digital-pathology-ai","ai-trial-matching"],"targets":[],"drugs":["artera-ai-breast"],"companies":["artera","tempus","owkin"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-chen-nat-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A multimodal model trained on trial cohorts predicts benefit from a specific therapy (e.g., TROP2 ADC vs chemotherapy) with clinically useful discrimination beyond current biomarkers.","rationale":"ArteraAI showed single-modality models can be predictive; adding modalities and outcomes from randomised trials allows causal treatment-effect estimation.","test":"Train on completed phase 3 datasets (with sponsors), validate on held-out trials; prospective biomarker-stratified trial.","maturity":"preclinical-evidence"},{"id":"idea-moon-pro-ctcae-in-every-pivotal-trial","kind":"idea","name":"Patient-reported side-effects (PRO-CTCAE) collected and published in every registrational trial","aka":[],"tldr":"Doctors record only part of what patients suffer. Make it compulsory that patients report their own side-effects in every trial used to approve a drug, and that those data are published next to the doctor-graded ones.","summary":"Concordance between clinician-graded CTCAE and patient-reported symptoms is poor, with clinicians systematically under-reporting frequency and severity of fatigue, nausea, neuropathy and diarrhoea. The NCI PRO-CTCAE library provides validated items. The proposal is a regulatory requirement that registrational oncology trials collect a core PRO-CTCAE set with weekly frequency during treatment, and that results appear in the primary publication and public assessment report in a standard table.","asOf":"2026-09-08","links":[{"label":"NCI PRO-CTCAE","url":"https://healthcaredelivery.cancer.gov/pro-ctcae/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Mandated PRO-CTCAE reveals substantially higher symptomatic toxicity than CTCAE tables for most regimens and changes comparative judgements between regimens with similar efficacy.","rationale":"Selective reporting persists because it is allowed. Standardised collection with a publication requirement is the cheapest fix and has precedent in CONSORT-PRO.","test":"Audit the PRO-CTCAE to CTCAE discordance across the first twenty trials under the rule; survey guideline committees on whether the data changed recommendations.","maturity":"being-tested-at-scale","actor":"regulator","cost":"small","horizonYears":2},{"id":"idea-data-pro-as-structured-standard","kind":"idea","name":"Patient-reported symptoms captured as standard structured data in every clinic","aka":[],"tldr":"Every cancer clinic would collect patients' own reports of symptoms and quality of life through a standard questionnaire that feeds straight into the record and into research datasets.","summary":"Electronic patient-reported outcomes (ePRO) improved survival in a randomised trial (Basch et al., 2017) yet remain absent from most routine records and from almost all real-world datasets. The proposal standardises a minimal PRO set (PRO-CTCAE core items, EQ-5D-5L) as an mCODE profile, requires it in oncology EHR certification, and funds the clinic workflow. Toxicity and quality of life would then be available as a real-world endpoint at scale.","asOf":"2026-09-08","links":[{"label":"Basch et al., JAMA 2017 (ePRO and survival)","url":"https://jamanetwork.com/journals/jama/fullarticle/2630810"}],"tags":[],"related":[],"cancers":[],"sections":["ai-computation","supportive-care"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["real-world-evidence"],"trials":[],"people":[],"bottlenecks":["b-data-silos","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Standardised ePRO capture in more than 50 percent of oncology visits will make real-world toxicity comparisons between drugs possible and reveal quality-of-life differences invisible in registries.","rationale":"Symptom monitoring has trial-proven benefit for patients; the data infrastructure payoff is additional. Standardisation is what makes the data pool.","test":"Implement the standard PRO set at ten centres and compare response rates and data completeness with centres using bespoke tools; produce a first cross-centre real-world toxicity comparison for two competing regimens.","maturity":"being-tested-at-scale","actor":"clinic","cost":"medium","horizonYears":3},{"id":"idea-moon-trial-eligibility-at-every-decision","kind":"idea","name":"Patients are told which trials they qualify for at every treatment decision, in writing","aka":[],"tldr":"At each point where treatment is chosen, software checks the patient's record against open trials and the clinician must note which were discussed, so trials stop being something only some people hear about.","summary":"Fewer than one in ten adults with cancer enter trials, partly because eligibility is never checked. Structured records (mCODE) and trial registries with structured eligibility now allow automated pre-screening. The proposal is a documented eligibility check at each decision point, including trials at other centres, with the result shown to the patient in plain language and a referral pathway funded by the payer.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Patients lack understanding, navigation and agency): Basch et al., Overall survival results of a trial assessing patient-reported outcomes for symptom monitoring during routine cancer treatment (JAMA 2017)","url":"https://doi.org/10.1001/jama.2017.7156"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["ai-trial-matching"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-patient-voice","b-trial-enrolment"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Documented matching raises trial discussion rates to over 80% of decision points and doubles enrolment, with proportionally larger gains for minority and community patients.","rationale":"Trial offer is the single strongest determinant of enrolment; inequity in offer, not refusal, explains much under-representation.","test":"Cluster-randomised implementation in community oncology practices with matching software; endpoints trial discussion documentation, referral and enrolment by demographic group.","maturity":"early-clinical","actor":"engineering","cost":"medium","horizonYears":3},{"id":"idea-data-patient-facing-model-cards","kind":"idea","name":"Patients told which AI is used in their care, in plain language","aka":[],"tldr":"Every patient would be able to see which AI tools were used in their diagnosis or treatment plan, what they do, how well they work and how to question them.","summary":"Patients are rarely informed when AI has contributed to their diagnosis or plan. The proposal requires a patient-facing model card, drawn from the model registry, attached to the patient's record whenever an AI tool influences care: what the tool did, its validated performance in plain terms, the version, and how to request human review. This supports informed consent, builds trust and creates a feedback channel for errors.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (AI that is built but not validated or deployed): Wu et al., How medical AI devices are evaluated: limitations and recommendations from an analysis of FDA approvals (Nature Medicine 2021)","url":"https://doi.org/10.1038/s41591-021-01312-x"}],"tags":[],"related":["idea-data-clinical-ai-model-registry"],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-ai-validation","b-patient-voice"],"keyPapers":["paper-wu-nat-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Disclosure will not reduce acceptance of validated AI tools and will increase patient trust and reporting of suspected errors, providing a new post-market signal.","rationale":"Transparency about automated decisions is required in other domains (credit, employment) and surveys show patients want to know; disclosure is also a precondition for meaningful consent.","test":"Implement disclosure at three centres for one year; survey patient trust and acceptance versus centres without disclosure; count error reports attributable to patients.","maturity":"speculative","actor":"patients","cost":"small","horizonYears":2},{"id":"idea-bio1-drug-holiday-resensitisation","kind":"idea","name":"Pause a failed drug so the tumour becomes sensitive to it again","aka":[],"tldr":"Resistant cancer cells can become dependent on the drug they resisted, as shown for BRAF-inhibitor-resistant melanoma in mice. Stopping the drug for a defined washout and then rechallenging, while tracking the resistance allele in blood tumour DNA, could make the tumour vulnerable to it once more.","summary":"Drug addiction has been demonstrated for BRAF-inhibitor-resistant melanoma in mice and reported anecdotally in patients rechallenged after a break. Intermittent dosing prevented resistance in those models. A prospective trial would formalise rechallenge: after progression and a defined washout with an intervening therapy, patients are rechallenged with the original agent and monitored with ctDNA for the resistance allele's decline during the holiday.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Acquired resistance to every therapy): Soria et al., Osimertinib in untreated EGFR-mutated NSCLC (FLAURA, NEJM 2018)","url":"https://doi.org/10.1056/NEJMoa1713137"}],"tags":[],"related":[],"cancers":["melanoma","nsclc"],"sections":[],"technologies":["liquid-biopsy"],"targets":[],"drugs":["encorafenib","osimertinib"],"companies":[],"institutions":[],"pathways":[],"terms":["resistance"],"trials":[],"people":[],"bottlenecks":["b-resistance","b-tumor-heterogeneity"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"The resistant clone fraction measured in plasma falls during a drug holiday, and rechallenge after a defined interval produces objective responses in a clinically meaningful minority of patients.","rationale":"The fitness cost of resistance mutations is a general evolutionary principle and is directly measurable in plasma, which makes the holiday duration optimisable rather than arbitrary.","test":"Phase 2 rechallenge study with serial ctDNA during the holiday in BRAF-mutant melanoma or EGFR-mutant lung cancer; endpoints response rate on rechallenge and correlation with clone decay kinetics.","maturity":"early-clinical","actor":"clinic","cost":"medium","horizonYears":4},{"id":"idea-reg-indication-specific-pricing","kind":"idea","name":"Pay a different price for the same cancer drug depending on the indication","aka":[],"tldr":"One immunotherapy may add years of life in one cancer and weeks in another, yet costs the same. Prices should track the benefit in each use.","summary":"Multi-indication oncology drugs are priced at a single level, so payers either overpay for low-value indications or refuse them entirely. Indication-based pricing has been implemented through Italy's AIFA web-based registries and, in effect, through confidential indication-level rebates in some markets; the barrier elsewhere is that claims do not reliably record the indication. The proposal is mandatory indication coding at dispensing (linking the diagnosis code and line of therapy to the drug claim) and indication-level net prices set from value frameworks such as ESMO-MCBS or ICER thresholds.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Prices and value): Prasad, De Jesús & Mailankody, The high price of anticancer drugs: origins, implications, barriers, solutions (Nat Rev Clin Oncol 2017)","url":"https://doi.org/10.1038/nrclinonc.2017.31"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":["pembrolizumab","olaparib"],"companies":[],"institutions":["esmo"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-drug-pricing"],"keyPapers":["paper-prasad-nat-rev-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Indication-specific pricing increases the number of reimbursed indications per multi-indication oncology drug and reduces average spend per quality-adjusted life year gained by at least 20% compared with uniform pricing.","rationale":"Value-based pricing is meaningless if value varies fivefold across uses and the price does not. Indication coding is a data problem that electronic prescribing has largely solved.","test":"Implement indication coding in one national or large regional payer for checkpoint inhibitors and PARP inhibitors, negotiate indication-level prices for two years, and compare reimbursed indications and spend per QALY with the prior period.","maturity":"early-clinical","actor":"payer","cost":"small","horizonYears":3},{"id":"idea-cost-asp-flat-fee","kind":"idea","name":"Pay a flat fee for giving a Part B drug instead of 6% of its price","aka":[],"tldr":"Medicare pays clinics the drug's average sales price plus 6%, so a dearer drug earns the clinic more; replacing the percentage with a flat handling fee removes the incentive to pick the expensive option.","summary":"Under Part B, clinician-administered drugs are reimbursed at the average sales price plus 6% (reduced by sequestration). The add-on scales with price, so two equally effective drugs earn a practice very different margins. A flat per-administration fee, set to cover handling and inventory cost, would make the choice between a biosimilar and its reference product, or between two similar checkpoint inhibitors, financially neutral for the prescriber. MedPAC has recommended variants of this for a decade.","asOf":"2026-09-10","links":[{"label":"CMS: Part B drug payment (ASP pricing files)","url":"https://www.cms.gov/medicare/payment/part-b-drugs/asp-pricing-files"},{"label":"MedPAC reports to Congress","url":"https://www.medpac.gov/document-type/report/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["nci"],"pathways":[],"terms":["biosimilar","340b-program"],"trials":[],"people":[],"bottlenecks":["b-drug-pricing","b-incentive-misalignment"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Switching the Part B add-on to a flat fee will raise biosimilar share in oncology by at least ten percentage points within two years and lower Part B oncology drug spending per patient without reducing the number of patients treated.","rationale":"The 340B and biosimilar literature shows prescribers respond to margins. Removing the margin difference is a cheaper lever than negotiating every price.","test":"A CMS Innovation Center model in a set of regions with a flat fee, comparing biosimilar share, drug spend and treatment volumes against matched control regions over two years.","maturity":"speculative","actor":"policy","cost":"medium","horizonYears":3},{"id":"idea-bio2-rare-cancer-prize-fund","kind":"idea","name":"Pay a prize for rare cancer drugs instead of hoping for a market","aka":[],"tldr":"No company can profit from a drug for a cancer that affects a few hundred people. A guaranteed payment for success would change that calculation.","summary":"Rare and paediatric cancers lack markets, and existing incentives (orphan designation, priority review vouchers, the proposed transferable exclusivity vouchers) are criticised for poor targeting and high cost to payers. A directly funded prize or advance market commitment, paid on achieving a pre-specified clinical benefit in a named rare indication, targets the payment to the outcome and avoids distorting prices elsewhere.","asOf":"2026-09-08","links":[{"label":"EMA orphan designation","url":"https://www.ema.europa.eu/en/human-regulatory-overview/orphan-designation-overview"}],"tags":[],"related":[],"cancers":["sarcoma","neuroblastoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["nci"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-rare-cancers","b-incentive-misalignment","b-funding-allocation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A pooled prize fund of a few hundred million dollars, with clearly specified indication targets and evidence thresholds, attracts at least five serious development programmes into rare cancers within five years, at lower total public cost than voucher schemes.","rationale":"Advance market commitments worked for pneumococcal vaccines, and prize mechanisms have produced results in other fields. Vouchers transfer cost opaquely to payers of unrelated drugs, whereas a prize is explicit and can be targeted at the exact unmet need.","test":"Model the cost of existing voucher schemes against an equivalent prize fund, then have one government or philanthropic consortium commit a single named prize for one rare indication and observe how many programmes enter.","maturity":"speculative","actor":"policy","cost":"large","horizonYears":8},{"id":"idea-cost-hypofractionation-payment","kind":"idea","name":"Pay for a course of radiotherapy, not for each fraction","aka":[],"tldr":"One week of breast radiotherapy in five doses works as well as three weeks in fifteen, but clinics paid per dose lose money by switching; paying one price per course removes the penalty.","summary":"FAST-Forward (Lancet 2020) showed 26 Gy in five fractions over one week was non-inferior to 40 Gy in fifteen fractions for local recurrence after breast surgery. Prostate, rectal, lung and palliative bone regimens have similar evidence. Fee-for-fraction payment makes the shorter course a revenue loss for the centre. Medicare's Radiation Oncology Model proposed episode payments; a simpler per-course rate for the common sites would align the incentive with the evidence.","asOf":"2026-09-10","links":[{"label":"Brunt et al., Lancet 2020: FAST-Forward","url":"https://doi.org/10.1016/S0140-6736(20)30932-6"}],"tags":[],"related":[],"cancers":["breast-hr-positive","prostate"],"sections":["radiation"],"technologies":["imrt-igrt","sbrt"],"targets":[],"drugs":[],"companies":[],"institutions":["astro"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-surgery-radiation-innovation","b-incentive-misalignment","b-knowledge-diffusion"],"keyPapers":["paper-murray-brunt-lancet"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Per-course payment will raise the share of eligible breast and prostate patients treated with five or fewer fractions to above 70% within two years, with lower total cost and equal control rates.","rationale":"Where payment is per patient rather than per fraction (the NHS, Canadian provinces) ultra-hypofractionation became standard within a few years of the trials.","test":"A payer pilot with per-course payment in selected regions, comparing fraction numbers, costs, patient travel and local control against fee-for-fraction regions.","maturity":"being-tested-at-scale","actor":"payer","cost":"small","horizonYears":2},{"id":"idea-data-ai-reimbursement-tied-to-outcomes","kind":"idea","name":"Pay for cancer AI only when it has outcome evidence, then pay properly","aka":[],"tldr":"Health systems would pay for AI tools that have shown in trials that they help patients, and pay nothing for tools that have not, giving makers a reason to run the trials.","summary":"Reimbursement for AI is haphazard: a few tools have billing codes on weak evidence, most have none, so vendors sell on workflow rather than outcomes. The proposal is a payer policy: a temporary payment for AI under coverage with evidence development while a prospective trial runs, converting to durable payment if outcome evidence is positive and ending if not, with payment levels reflecting demonstrated value. Medicare's coverage decisions for a handful of AI devices are a starting point.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (AI that is built but not validated or deployed): Wu et al., How medical AI devices are evaluated: limitations and recommendations from an analysis of FDA approvals (Nature Medicine 2021)","url":"https://doi.org/10.1038/s41591-021-01312-x"}],"tags":[],"related":["idea-data-prospective-ai-trials-fund"],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-ai-validation","b-incentive-misalignment"],"keyPapers":["paper-wu-nat-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Outcome-conditional reimbursement will increase the number of prospective AI trials started per year and shift the market toward tools with demonstrated benefit.","rationale":"Payment is the strongest signal to developers; where payers required evidence (e.g., for genomic tests via Medicare's MolDX), evidence generation followed.","test":"One national payer adopts the policy for two years; count AI trials initiated and tools reaching durable coverage versus the prior period.","maturity":"speculative","actor":"payer","cost":"medium","horizonYears":3},{"id":"idea-tr2-biomarker-cwe","kind":"idea","name":"Pay for new biomarker tests only while evidence of clinical utility is being collected","aka":[],"tldr":"Most genomic and liquid biopsy tests are reimbursed on analytical validity and association with outcome, not on proof that they improve care. Paying for new oncology biomarker tests only inside registries or randomised studies, as Medicare did for PET, would sort the useful from the useless.","summary":"Most genomic and liquid biopsy tests are reimbursed on analytical validity and association with outcome, not on demonstrated clinical utility. Coverage with evidence development, used by Medicare for PET and for some genomic tests, ties payment to enrolment in a registry or randomised study. Applying it systematically to new oncology biomarker tests would generate utility evidence at the scale of routine practice and remove payment for tests that fail.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Biomarkers are not validated or standardised): Fernandez et al., Examination of low ERBB2 protein expression in breast cancer tissue (JAMA Oncology 2022)","url":"https://doi.org/10.1001/jamaoncol.2021.7239"}],"tags":[],"related":["idea-tr2-payer-combo-cwe"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["real-world-evidence","companion-diagnostic-term"],"trials":[],"people":[],"bottlenecks":["b-biomarker-validation","b-drug-pricing"],"keyPapers":["paper-fernandez-jama-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Tests entered into coverage-with-evidence programmes will reach a definitive utility answer within four years in at least half of cases, and at least a quarter will lose coverage on the evidence.","rationale":"The National Oncologic PET Registry produced evidence that changed coverage for FDG PET; the model has been under-used for molecular tests.","test":"Apply the programme to three new tests in one payer; measure time to evidence and coverage decisions.","maturity":"early-clinical","actor":"payer","cost":"medium","horizonYears":3},{"id":"idea-reg-annuity-payment-durable-therapies","kind":"idea","name":"Pay for one-time curative therapies as an annuity that stops at relapse","aka":[],"tldr":"A single cell therapy can cost more than a house. Paying in yearly instalments, only while the patient stays well, spreads the cost and shares the risk.","summary":"Single-administration therapies with durable but uncertain benefit strain annual budgets and shift all risk of relapse to the payer. Annuity or performance-linked instalment models have been implemented for gene therapies for rare diseases in the US and Europe (for example for spinal muscular atrophy and haemophilia), with payments contingent on continued response. The proposal is to make annuity contracts standard for oncology cell therapies with curative intent: a fixed payment at infusion covering manufacturing, then annual payments for up to five years while the patient remains in remission, adjudicated through the treatment registry.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Prices and value): Prasad, De Jesús & Mailankody, The high price of anticancer drugs: origins, implications, barriers, solutions (Nat Rev Clin Oncol 2017)","url":"https://doi.org/10.1038/nrclinonc.2017.31"}],"tags":[],"related":["idea-reg-cart-outcomes-refund"],"cancers":[],"sections":[],"technologies":["car-t"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-drug-pricing","b-manufacturing-cell-therapy"],"keyPapers":["paper-prasad-nat-rev-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Annuity contracts increase the number of centres and payers offering CAR-T (especially smaller insurers and middle-income systems) and reduce payer spend on patients who relapse early by more than 50%.","rationale":"Aligning cash flows with realised benefit removes both the budget-impact barrier and the risk barrier that keep durable therapies out of many systems; registries make remission status verifiable at low cost.","test":"Pilot annuity contracts for CAR-T in lymphoma with two payers and one or two manufacturers for three years; compare uptake and spend per durable remission with fixed-price contracts.","maturity":"early-clinical","actor":"payer","cost":"small","horizonYears":3},{"id":"idea-acc-linac-uptime-contracts","kind":"idea","name":"Pay for radiotherapy machine uptime, not for the machine","aka":[],"tldr":"Governments and donors should buy guaranteed working hours from radiotherapy vendors, with remote monitoring and regional spare-parts depots, instead of buying machines that then sit broken.","summary":"Radiotherapy machines in low- and middle-income countries are frequently non-operational for months awaiting a part or a visiting engineer. A regional shared-service model would bundle continuous remote diagnostics, an in-region spare-parts depot, and locally trained engineers into a multi-country service contract with penalties for downtime. Vendors already run remote monitoring in high-income markets; the change is contractual, not technical.","asOf":"2026-09-08","links":[{"label":"IAEA Rays of Hope","url":"https://www.iaea.org/services/rays-of-hope"}],"tags":[],"related":[],"cancers":[],"sections":["radiation"],"technologies":[],"targets":[],"drugs":[],"companies":["varian","elekta"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-global-access","b-surgery-radiation-innovation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Uptime-linked service contracts covering a regional cluster of at least ten machines will raise annual scheduled-hours delivered by at least 30% within two years compared with machines under standard warranty terms.","rationale":"Availability-based contracting transformed aircraft-engine and hospital-imaging maintenance economics. Concentrating demand across countries makes an in-region engineer and parts depot affordable.","test":"A donor-backed pilot across one region (e.g., East Africa) comparing uptime, mean time to repair, and patients treated per machine between contracted and non-contracted sites, reported quarterly and published.","maturity":"early-clinical","actor":"policy","cost":"medium","horizonYears":3},{"id":"idea-bio2-mrd-coverage-with-evidence","kind":"idea","name":"Pay for residual disease tests only inside a trial or registry","aka":[],"tldr":"Leftover-cancer blood tests are being sold faster than evidence that acting on them helps. Paying for them only when the result is recorded would generate the missing evidence.","summary":"MRD testing is spreading through routine care ahead of randomised evidence that intervention on a positive result improves survival. Coverage with evidence development (reimbursement conditional on enrolment in a registry or trial with mandatory outcome submission) turns uncontrolled adoption into a data-generating engine, as it has for some devices and PET indications.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Dormant cells and minimal residual disease): Tie et al., ctDNA analysis guiding adjuvant therapy in stage II colon cancer (NEJM 2022)","url":"https://doi.org/10.1056/NEJMoa2200075"}],"tags":[],"related":["seer","clinicaltrials-gov"],"cancers":[],"sections":[],"technologies":["mrd-testing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["real-world-evidence"],"trials":[],"people":[],"bottlenecks":["b-dormancy-mrd","b-real-world-evidence","b-incentive-misalignment"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Conditional coverage produces an analysable dataset of over 50,000 tested patients with linked outcomes within three years, and identifies at least one tumour setting where MRD-guided intervention does not help.","rationale":"The National Oncologic PET Registry showed that conditional coverage can produce practice-changing evidence quickly at low cost. The alternative, unconditional payment, has repeatedly left the field with widespread use and no answer.","test":"One national payer or insurer pilots conditional coverage for one tumour type, publishing enrolment, completeness of outcome capture and cost per patient after 18 months.","maturity":"speculative","actor":"payer","cost":"small","horizonYears":3},{"id":"idea-bio2-exercise-reimbursement","kind":"idea","name":"Pay for supervised exercise the way we pay for drugs","aka":[],"tldr":"A large trial showed a structured exercise programme improved survival after bowel cancer. Almost no health system pays for it, so almost no patient gets it.","summary":"A randomised trial of a three-year structured exercise programme after colon cancer chemotherapy reported improved disease-free survival, an effect size comparable with some adjuvant drugs at a small fraction of the cost. Reimbursement codes, referral pathways and trained providers are the barriers. Cardiac rehabilitation is the working template for how a supervised exercise service can be funded and audited at scale.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Cachexia, toxicity and the limits of the patient): Fearon et al., Definition and classification of cancer cachexia (Lancet Oncology 2011)","url":"https://doi.org/10.1016/S1470-2045(10)70218-7"}],"tags":[],"related":["idea-exercise-as-adjuvant"],"cancers":["colorectal","breast-hr-positive","prostate"],"sections":[],"technologies":["exercise-oncology"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-cachexia-supportive","b-survivorship","b-incentive-misalignment"],"keyPapers":["paper-fearon-lancet-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Introducing a reimbursed structured exercise benefit for curative-intent cancer patients achieves at least 40% uptake and is cost-saving within five years through reduced recurrence and hospital use.","rationale":"Cardiac rehabilitation moved from trial evidence to funded service with measurable population benefit, and the delivery model transfers directly. Exercise also improves treatment tolerance, which supports dose intensity.","test":"A payer pilot in one region with a defined benefit and mandatory registry; measure uptake, adherence, treatment completion rates and total cost of care against matched controls.","maturity":"early-clinical","actor":"payer","cost":"medium","horizonYears":4},{"id":"idea-prev-pay-for-prevention-outcomes","kind":"idea","name":"Pay insurers and health systems for cancers prevented and caught early","aka":[],"tldr":"Health systems earn from treating cancer, not preventing it. Paying them for lower cancer incidence and earlier stage in their population would flip the incentive.","summary":"Health systems earn from treating cancer rather than preventing it, so this idea pays capitated insurers and health systems for cancers prevented and caught early, through outcome payments tied to population stage distribution, HPV vaccination coverage and smoking prevalence, adjusted for risk. Fee-for-service rewards volume, whereas outcome-based contracts change practice in other areas of care. The aim is higher screening and vaccination coverage and a stage shift towards stage I-II. The test is a payer pilot of a prevention outcomes bundle in a capitated system such as a Medicare Advantage plan or an NHS integrated care board. Speculative in maturity, it addresses the bottlenecks Prevention we already have is not deployed and Incentives reward me-too drugs and marginal gains.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Prevention we already have is not deployed): Islami et al., Proportion of cancer attributable to modifiable risk factors (CA 2018)","url":"https://doi.org/10.3322/caac.21440"}],"tags":[],"related":[],"cancers":[],"sections":["prevention"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["stage-shift"],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption","b-incentive-misalignment"],"keyPapers":["paper-islami-ca-cancer-j-clin"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Outcome payments raise screening and vaccination coverage by at least 10 points and shift stage at diagnosis toward stage I-II by at least 5 points within five years.","rationale":"Fee-for-service rewards volume; outcome-based contracts change behaviour in other areas of care.","test":"Pilot in a capitated system (a Medicare Advantage plan or NHS integrated care board).","maturity":"speculative","actor":"payer","cost":"medium","horizonYears":5},{"id":"idea-fund-trial-completion-bonus","kind":"idea","name":"Pay investigators for finishing and publishing trials, not for enrolling patients","aka":[],"tldr":"Trial sites are paid per patient recruited, so nobody is paid to finish the study or report the answer. Shift part of the payment to completion and publication within a year.","summary":"Sponsors and public funders restructure site and investigator payments so that a meaningful share (for example 25%) is held back and paid on completion of follow-up, database lock and public results posting within twelve months of the primary completion date, with a further bonus for peer-reviewed publication of negative results. Academic centres pass this through to investigator research accounts. Trial non-reporting remains common years after completion, and academic trials in particular stall in analysis and writing because the incentive ends with the last patient.","asOf":"2026-09-08","links":[{"label":"EU Trials Tracker","url":"https://eu.trialstracker.net/"}],"tags":[],"related":["clinicaltrials-gov","eudract-ctis","idea-fund-academic-promotion-reform","idea-fund-programme-officer-incentives"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-incentive-misalignment","b-negative-results","b-trial-enrolment"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Completion- and reporting-linked payments raise the share of trials with results posted within twelve months of primary completion from the current minority to above 80% at participating sites, and reduce the analysis-to-publication interval by at least six months.","rationale":"Results reporting rose sharply where enforcement existed (the FDA Amendments Act compliance improved once penalties were publicised; the EU trials tracker shamed institutions into action). Money attached to the milestone is a stronger and cheaper lever than penalties.","test":"A public funder applies the payment structure to all trials in one funding round and compares reporting timeliness with the previous round.","maturity":"speculative","actor":"clinic","cost":"small","horizonYears":2},{"id":"idea-tr1-protected-physician-time-for-enrolment","kind":"idea","name":"Pay oncologists for the time it takes to enrol a patient","aka":[],"tldr":"Discussing and enrolling a patient in a trial takes an oncologist far longer than prescribing the usual treatment, and they are not paid for it. Paying for that time would remove a quiet disincentive.","summary":"Health systems and payers create a reimbursable code or protected-time allocation for trial discussion and enrolment (analogous to advance-care-planning codes), and sponsors' per-patient budgets include physician time explicitly rather than folding it into overhead. Academic promotion criteria count enrolment.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Trials enrol too few, too slowly): Unger et al., Systematic review of barriers to cancer trial participation (JNCI 2019)","url":"https://doi.org/10.1093/jnci/djy221"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["asco"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-enrolment","b-incentive-misalignment"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Practices where physician enrolment time is paid or protected will have higher enrolment per oncologist than matched practices without it.","rationale":"Physician recommendation is the strongest predictor of enrolment, and time pressure is the most cited reason oncologists do not offer trials. Payment for cognitive services changes behaviour in other settings.","test":"A health system introduces a trial-discussion payment for half its oncology practices for 18 months and compares enrolment per physician.","maturity":"speculative","actor":"payer","cost":"medium","horizonYears":2},{"id":"idea-fund-course-based-radiotherapy-payment","kind":"idea","name":"Pay per course of radiotherapy, not per session, so short courses are not penalised","aka":[],"tldr":"Hospitals are paid for each radiotherapy session, so a proven five-session course earns less than an unproven twenty-five-session one. Paying per course removes the reason to give more treatment than needed.","summary":"Payers move from per-fraction to episode-based or per-course payment for radiotherapy, with the price set by indication and independent of fraction number, and with a quality bonus for adherence to evidence-based fractionation guidelines. Randomised trials (FAST-Forward, CHHiP, PACE-B, the Dutch and Canadian hypofractionation trials) have shown that shorter courses are equivalent for breast and prostate cancer, yet uptake lags for years in fee-for-service systems. The US Radiation Oncology Model was designed on this principle; implementing it widely, and in other countries, aligns payment with evidence and frees capacity.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Surgery and radiotherapy cure most, get least): Sullivan et al., Global cancer surgery (Lancet Oncology Commission 2015)","url":"https://doi.org/10.1016/S1470-2045(15)00223-5"}],"tags":[],"related":["idea-fund-radiotherapy-trials-infrastructure","idea-fund-payer-funded-pragmatic-trials"],"cancers":["breast-hr-positive","prostate"],"sections":[],"technologies":["imrt-igrt","sbrt"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-surgery-radiation-innovation","b-incentive-misalignment"],"keyPapers":["paper-sullivan-lancet-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Course-based payment raises the use of guideline-concordant hypofractionation for breast and prostate cancer by at least 20 percentage points within two years in affected systems, with no measurable change in outcomes or toxicity.","rationale":"Uptake of hypofractionation is far higher in capitated or salaried systems (UK, Canada) than in fee-for-service settings, indicating payment, not evidence, drives practice. Episode payment is a standard tool for aligning incentives and requires no new evidence.","test":"Compare hypofractionation rates and outcomes before and after episode-based payment in a payer region against a matched fee-for-service region.","maturity":"being-tested-at-scale","actor":"payer","cost":"small","horizonYears":2},{"id":"idea-cost-site-neutral-infusion","kind":"idea","name":"Pay the same for an infusion whether it is given in a hospital or a clinic","aka":[],"tldr":"The same chemotherapy infusion costs payers and patients more in a hospital outpatient department than in a doctor's office; paying one rate would stop hospitals buying clinics to charge the higher price.","summary":"Hospital outpatient departments are paid under a separate, higher fee schedule and can add facility fees. As hospitals have acquired community oncology practices, infusions have moved to the dearer setting without any change in what is given. Site-neutral payment sets one price for the same service; Medicare applied it to clinic visits in 2019 and Congress has repeatedly considered extending it to drug administration.","asOf":"2026-09-10","links":[{"label":"CMS: Hospital Outpatient Prospective Payment System","url":"https://www.cms.gov/medicare/payment/prospective-payment-systems/hospital-outpatient"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["340b-program","financial-toxicity"],"trials":[],"people":[],"bottlenecks":["b-drug-pricing","b-incentive-misalignment","b-care-fragmentation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Site-neutral payment for chemotherapy administration and imaging will cut Medicare and patient spending for those services by at least a fifth in hospital-owned sites without measurable change in safety or access.","rationale":"The clinical service is identical; the price difference is a payment rule. Medicare's 2019 clinic-visit change reduced spending as modelled.","test":"Phase in site-neutral rates for infusion codes in Medicare and track spending, patient coinsurance, infusion volumes and hospital acquisitions of practices against the prior trend.","maturity":"being-tested-at-scale","actor":"policy","cost":"medium","horizonYears":3},{"id":"idea-tr1-pay-participants-for-time","kind":"idea","name":"Pay trial participants for their time, not only their expenses","aka":[],"tldr":"Trial visits take hours and cost people wages. Paying a fair hourly rate for time spent beyond normal care would make trials possible for those who cannot afford unpaid days off.","summary":"Participants receive a wage-equivalent payment for research-only time (extra visits, procedures, questionnaires), set to a local living wage, disclosed in consent, and paid regardless of completion to avoid coercion to continue. Ethics guidance would treat payment for time as ethically required rather than suspect. Test whether it shifts who enrols.","asOf":"2026-09-08","links":[{"label":"FDA: Payment and Reimbursement to Research Subjects","url":"https://www.fda.gov/regulatory-information/search-fda-guidance-documents/payment-and-reimbursement-research-subjects"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-enrolment","b-trial-diversity"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Offering wage-equivalent payment for time increases enrolment of working-age and lower-income patients without increasing early withdrawal or misreporting of eligibility.","rationale":"Healthy-volunteer trials pay for time routinely; the refusal to pay cancer patients rests on a concern about undue influence that empirical studies have not supported. Lost wages are cited as a barrier as often as travel.","test":"Randomise sites within a large trial to offer or not offer time payment; compare enrolment demographics, refusal reasons and retention.","maturity":"speculative","actor":"policy","cost":"medium","horizonYears":2},{"id":"idea-moon-pay-for-cure-contracts","kind":"idea","name":"Pay-for-cure contracts: instalment payments for curative therapies contingent on durable remission","aka":[],"tldr":"For very expensive one-time treatments such as CAR-T, pay in instalments over years and stop paying if the cancer comes back, so price tracks the cure actually delivered.","summary":"One-time curative-intent therapies (CAR-T, gene therapies, potentially in vivo cell therapy) carry prices that health systems struggle to absorb up front and that are not tied to durability. Outcome-based agreements exist in a few countries. The proposal is a standard contract framework: payments spread over five years, annual instalments contingent on registry-verified remission, portability across payers when patients move, and public reporting of durability, with the same framework offered in middle-income countries at tiered prices.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Prices and value): Prasad, De Jesús & Mailankody, The high price of anticancer drugs: origins, implications, barriers, solutions (Nat Rev Clin Oncol 2017)","url":"https://doi.org/10.1038/nrclinonc.2017.31"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["car-t"],"targets":[],"drugs":["axicabtagene-ciloleucel","ciltacabtagene-autoleucel"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-drug-pricing","b-incentive-misalignment"],"keyPapers":["paper-prasad-nat-rev-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Pay-for-cure contracts increase the number of patients treated with curative therapies by a third at the same budget and shift manufacturer investment toward durability of response.","rationale":"Aligning payment with the outcome that matters removes the payer's risk on unproven durability and rewards manufacturers for cures rather than infusions.","test":"Implement for CAR-T in two national payers; compare patients treated, budget impact and durability data quality against payers using up-front payment.","maturity":"early-clinical","actor":"payer","cost":"medium","horizonYears":4},{"id":"idea-fund-omission-deescalation-trials","kind":"idea","name":"Payer-funded trials that omit surgery or radiotherapy in low-risk patients","aka":[],"tldr":"Low-risk patients often receive operations and radiotherapy they may not need, for example sentinel node biopsy in older women with favourable breast cancer or radiotherapy after breast-conserving surgery in genomically low-risk disease. Because no company will sponsor trials of leaving treatment out, health systems should fund them and keep the savings.","summary":"Payers and public funders sponsor randomised trials of omission or de-escalation of local therapy: omitting sentinel node biopsy in older women with favourable breast cancer (as SOUND and INSEMA tested), omitting radiotherapy after breast-conserving surgery in genomically low-risk disease, active surveillance instead of surgery in low-risk thyroid and prostate cancer, and shorter or lower-dose regimens. These trials save money, reduce harm and address overdiagnosis, but have no commercial sponsor. Genomic and imaging biomarkers now allow risk-adapted selection that makes omission trials ethically and statistically feasible.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Surgery and radiotherapy cure most, get least): Sullivan et al., Global cancer surgery (Lancet Oncology Commission 2015)","url":"https://doi.org/10.1016/S1470-2045(15)00223-5"}],"tags":[],"related":["idea-fund-organ-preservation-programme","idea-fund-payer-funded-pragmatic-trials","idea-til-guided-deescalation"],"cancers":["breast-hr-positive","thyroid","prostate"],"sections":[],"technologies":["sentinel-node","imrt-igrt"],"targets":[],"drugs":["oncotype-dx"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-surgery-radiation-innovation","b-toxicity-qol","b-overdiagnosis"],"keyPapers":["paper-sullivan-lancet-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A payer-funded omission programme produces at least four practice-changing results within six years, each reducing the number of procedures or radiotherapy courses in the target population by a fifth or more with non-inferior recurrence.","rationale":"SOUND, INSEMA, PRIME II and the low-risk DCIS trials have shown omission is safe in defined groups and changed guidelines; each was funded with difficulty by academic grants. Payers are the natural sponsors because the savings accrue to them directly.","test":"A payer trials fund launches two omission trials and pre-registers projected savings; audit realised savings and outcome non-inferiority at trial completion.","maturity":"being-tested-at-scale","actor":"payer","cost":"medium","horizonYears":4},{"id":"idea-tr2-payer-combo-cwe","kind":"idea","name":"Payers cover off-label combinations only inside registry-randomised trials","aka":[],"tldr":"Insurers already pay for off-label drug combinations that have never been randomised. Paying only when the patient joins a registry-based randomised comparison, as Medicare did for devices and the Cancer Drugs Fund did for cancer drugs, would turn that spending into evidence at no new drug cost.","summary":"Coverage with evidence development has been used by Medicare for devices and by NICE for cancer drugs through the Cancer Drugs Fund. Applying it to off-label combinations would fund a large pragmatic randomised programme with no new drug costs, since the drugs would be paid for anyway, and would end reimbursement of combinations that fail.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Too many combinations to test): Palmer & Sorger, Combination cancer therapy can confer benefit via patient-to-patient variability without drug additivity or synergy (Cell 2017)","url":"https://doi.org/10.1016/j.cell.2017.11.009"}],"tags":[],"related":["idea-tr2-pragmatic-sequence-randomisation"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["real-world-evidence"],"trials":[],"people":[],"bottlenecks":["b-combination-space","b-drug-pricing"],"keyPapers":["paper-palmer-cell"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A coverage-with-evidence programme for off-label combinations will randomise at least 5,000 patients per year in one large payer and produce a definitive result for at least two combinations within four years.","rationale":"The Cancer Drugs Fund's managed access showed payers can collect evidence as a condition of payment; randomisation is the missing step.","test":"Pilot with one payer and two common off-label combinations with documented equipoise; measure enrolment, cost neutrality and time to answer.","maturity":"speculative","actor":"payer","cost":"medium","horizonYears":4},{"id":"idea-data-coverage-with-evidence-development","kind":"idea","name":"Payers fund cancer drugs conditionally on a registry with a pre-specified analysis","aka":[],"tldr":"When a health system pays for a new, uncertain cancer drug, it would require that every patient's outcome is recorded and that a pre-agreed analysis decides whether payment continues.","summary":"Coverage with evidence development exists (the English Cancer Drugs Fund, Medicare CED, Italy's AIFA registries) but analyses are often weak, late or never published. The proposal standardises the model: a pre-registered statistical analysis plan agreed at listing, mandatory structured data capture, an independent analysis body, a fixed decision date, and publication of results whatever the outcome.","asOf":"2026-09-08","links":[{"label":"NICE Cancer Drugs Fund","url":"https://www.england.nhs.uk/cancer/cdf/"}],"tags":[],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["real-world-evidence"],"trials":[],"people":[],"bottlenecks":["b-real-world-evidence","b-drug-pricing"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Standardised CED with pre-specified analyses will produce a reimbursement decision for more than 90 percent of conditionally funded indications within three years, and will lead to withdrawal or price reduction in a meaningful share.","rationale":"The reformed Cancer Drugs Fund (2016) cleared its backlog by fixing decision dates and data collection; AIFA registries have supported outcome-based rebates. Standardising the analytic component is the missing piece.","test":"Audit all CED decisions in three systems over five years for timeliness and publication; introduce the standardised model in one and compare.","maturity":"being-tested-at-scale","actor":"payer","cost":"medium","horizonYears":3},{"id":"idea-fund-payer-funded-pragmatic-trials","kind":"idea","name":"Payers fund trials of cheaper, shorter or lower-dose versions of expensive treatments","aka":[],"tldr":"Health insurers and national health systems have every reason to find out whether half the dose or half the duration of a costly drug works as well. They would fund those trials directly and keep the savings.","summary":"Payers commission pragmatic randomised trials of dose reduction, shorter duration, extended dosing intervals, stopping rules and cheaper alternatives for high-cost oncology drugs, embedded in routine care with registry endpoints. No manufacturer will run these; academic groups lack money. Precedents include the UK's REFINE-Lung (reduced-frequency pembrolizumab), the Netherlands' payer-supported trials of lower-dose abiraterone and dose-reduced ibrutinib, and the Dutch SONIA trial on CDK4/6 sequencing, whose savings dwarfed its cost. A standing payer trials fund with a savings-reinvestment rule would make this systematic.","asOf":"2026-09-08","links":[{"label":"FDA Project Optimus","url":"https://www.fda.gov/about-fda/oncology-center-excellence/project-optimus"}],"tags":[],"related":["idea-fund-implementation-quota","idea-fund-duration-trial-exclusivity","idea-fund-older-patients-trial-fund"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":["pembrolizumab","palbociclib","ribociclib"],"companies":[],"institutions":["nki"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-incentive-misalignment","b-dose-optimisation","b-drug-pricing"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A payer trials fund of $50 million a year yields treatment-modification results whose first-year savings exceed the fund's total cost, without loss of efficacy in non-inferiority designs, for at least two of the first five trials.","rationale":"SONIA showed that deferring CDK4/6 inhibitors saved months of toxicity and large costs with no survival difference; dose-optimisation trials of abiraterone with food and of ibrutinib have shown equivalence at a fraction of the dose. Payer-funded research is standard in some countries (ZonMw in the Netherlands, NIHR HTA in the UK) but rare in oncology elsewhere.","test":"Establish the fund in one system, run five pragmatic trials with pre-specified savings estimates, and audit realised savings versus fund cost after four years.","maturity":"early-clinical","actor":"payer","cost":"medium","horizonYears":4},{"id":"idea-reg-payer-coverage-off-label-generic-commitment","kind":"idea","name":"Payers pre-commit to cover off-label generics when a definitive trial is positive","aka":[],"tldr":"Even when a trial proves a cheap old drug helps, insurers may refuse to pay because it is not licensed for cancer. A standing promise to pay would remove that fear.","summary":"Uncertainty about reimbursement discourages trialists and clinicians and leaves proven repurposed treatments unused. The proposal is a formal coverage policy, adopted by public payers and large insurers, stating that any off-patent drug shown in a registration-quality randomised trial to improve survival or a validated patient-relevant endpoint in cancer will be covered for that use within six months of publication, subject to an independent evidence review, regardless of label status. The policy is published in advance so trial funders can rely on it.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (No incentive to repurpose cheap drugs): Pantziarka et al., The Repurposing Drugs in Oncology (ReDO) Project (ecancer 2014)","url":"https://doi.org/10.3332/ecancer.2014.442"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-generic-repurposing","b-incentive-misalignment"],"keyPapers":["paper-pantziarka-ecancermedicalscience"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Payers adopting the policy see faster uptake of proven repurposed interventions and the policy is cited by funders as a reason for funding new repurposing trials.","rationale":"Coverage is the endpoint that matters for a generic drug; guaranteeing it in advance turns a speculative trial into a fundable one and removes the last excuse for non-use after a positive result.","test":"Adopt the policy in two public payers; measure time from publication to coverage for the next positive repurposing trials and survey funders about its influence.","maturity":"speculative","actor":"payer","cost":"small","horizonYears":2},{"id":"idea-moon-quality-adjusted-pricing","kind":"idea","name":"Payers price drugs on quality-adjusted benefit, so toxicity costs the manufacturer","aka":[],"tldr":"If two drugs extend life equally but one makes patients much sicker, the health system should pay less for the sicker one. Build that into how prices are set.","summary":"Health technology assessment uses quality-adjusted life-years in principle, but in oncology practice utilities are poorly measured and toxicity rarely moves the price. The proposal is an explicit tolerability adjustment in pricing and reimbursement: standardised patient-reported tolerability data from trials feed a published formula that discounts the price for excess symptomatic toxicity and time toxicity relative to comparators, with the discount revisited as real-world PRO data accrue.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Toxicity and quality of life are undervalued): Di Maio et al., Symptomatic toxicities experienced during anticancer treatment: agreement between patient and physician reporting (JCO 2015)","url":"https://doi.org/10.1200/JCO.2014.57.9334"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol","b-drug-pricing"],"keyPapers":["paper-di-maio-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A transparent toxicity price adjustment shifts industry investment toward better-tolerated agents and dosing within one product cycle, measurable as declining grade 3+ and PRO-CTCAE severe rates in newly approved drugs.","rationale":"Manufacturers respond to price signals more reliably than to guidance; today the signal on toxicity is close to zero.","test":"A national payer publishes and applies the adjustment for two years; compare submitted tolerability data quality and pipeline dose-optimisation activity against payers without it.","maturity":"speculative","actor":"payer","cost":"small","horizonYears":3},{"id":"idea-payload-switching","kind":"idea","name":"Payload-class switching as the rule for ADC sequencing","aka":[],"tldr":"When one ADC fails, the next should carry a different kind of poison, not just aim at a different protein.","summary":"When one ADC fails, the next should carry a different kind of payload rather than simply aim at a different antigen. Patients progressing on a TOP1-payload ADC are expected to do better on a following ADC with a tubulin, DNA-crosslinker or degrader payload than on a second TOP1 ADC regardless of target, because SLFN11 loss, TOP1 mutations and ABCG2 upregulation are payload-level resistance mechanisms shared by DXd, SN-38 and exatecan derivatives. A randomised sequencing trial in HER2-low or TNBC after T-DXd or sacituzumab govitecan would compare the two strategies and measure SLFN11 and TOP1 status on progression biopsies. With preclinical evidence so far, it addresses the bottlenecks Acquired resistance to every therapy and Too many combinations to test.","asOf":"2026-09-04","links":[{"label":"ASCENT: sacituzumab govitecan doubles survival in heavily pretreated metastatic triple-negative breast cancer (New England Journal of Medicine 2021)","url":"https://doi.org/10.1056/NEJMoa2028485"},{"label":"DESTINY-Breast03: trastuzumab deruxtecan beats T-DM1 as second-line treatment of HER2-positive metastatic breast cancer (New England Journal of Medicine 2022)","url":"https://doi.org/10.1056/NEJMoa2115022"}],"tags":[],"related":["adc-after-adc-caution"],"cancers":["tnbc","breast-hr-positive"],"sections":[],"technologies":["adc","dual-payload-adc","topoisomerase-inhibitors"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["adc-sequencing","efflux-pump"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"In patients progressing on a TOP1-payload ADC, a next ADC with a non-TOP1 payload yields longer PFS than a second TOP1-payload ADC regardless of antigen.","rationale":"SLFN11 loss, TOP1 mutations, and ABCG2 upregulation are payload-level resistance mechanisms shared by DXd, SN-38, and exatecan derivatives.","test":"A randomised sequencing trial in HER2-low/TNBC after T-DXd or sacituzumab: MMAE- or non-TOP1-payload ADC vs alternate TOP1 ADC; measure SLFN11 and TOP1 status on progression biopsies as predictive biomarkers.","maturity":"preclinical-evidence"},{"id":"idea-reg-perioperative-propranolol-etodolac","kind":"idea","name":"Perioperative beta-blocker plus COX-2 inhibitor to reduce metastasis after surgery","aka":[],"tldr":"Surgical stress releases catecholamines and prostaglandins that suppress anti-tumour immunity and help metastatic cells seed. Phase 2 trials of a five-day course of propranolol plus etodolac around breast and colorectal surgery shifted tumour markers of metastasis and immune suppression in the right direction; both drugs cost cents, and a publicly funded phase 3 is the missing step.","summary":"Surgical stress releases catecholamines and prostaglandins that suppress anti-tumour immunity and promote metastatic seeding in animal models. Phase 2 trials of propranolol plus etodolac around surgery in breast and colorectal cancer (Ben-Eliyahu and colleagues) showed favourable changes in tumour transcriptomic markers of metastasis and immune suppression, and a small colorectal trial suggested reduced recurrence. Both drugs cost cents. The proposal is a publicly funded, multinational phase 3 in colorectal and breast cancer with disease-free survival as the primary endpoint.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (No incentive to repurpose cheap drugs): Pantziarka et al., The Repurposing Drugs in Oncology (ReDO) Project (ecancer 2014)","url":"https://doi.org/10.3332/ecancer.2014.442"}],"tags":[],"related":[],"cancers":["colorectal","breast-hr-positive"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-generic-repurposing","b-metastasis-biology"],"keyPapers":["paper-pantziarka-ecancermedicalscience"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Perioperative propranolol and etodolac for about five days improve 5-year disease-free survival by an absolute 5 percentage points or more in stage II-III colorectal cancer compared with placebo.","rationale":"The biology is well characterised, the intervention is short, and the perioperative window is a plausible point of vulnerability for micrometastatic disease that no expensive therapy targets.","test":"Phase 3 randomised placebo-controlled trial of roughly 1,500 patients in colorectal cancer with DFS primary endpoint and recurrence transcriptomic biomarkers in a sub-study.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":6},{"id":"idea-peritoneal-directed-gastric","kind":"idea","name":"Peritoneal-directed therapy for gastric cancer","aka":[],"tldr":"Stomach cancer usually comes back on the abdominal lining, where drugs barely reach. Deliver treatment directly into the abdomen.","summary":"Gastric cancer most often recurs on the peritoneum, where systemic drugs barely reach, so this idea proposes delivering treatment directly into the abdomen. Candidates include intraperitoneal paclitaxel with systemic chemotherapy, which PHOENIX-GC narrowly missed and Japanese trials are pursuing, PIPAC, and regionally delivered CLDN18.2 CAR-T such as satricabtagene autoleucel. The rationale is the pharmacokinetic advantage of intraperitoneal delivery and the fact that peritoneal-only disease is a distinct, chemoresistant compartment that staging laparoscopy can identify early. The proposed test is a randomised phase 3 restricted to peritoneal-only disease, and at an early clinical stage it addresses the bottleneck that metastasis is understood least and studied last.","asOf":"2026-09-07","links":[{"label":"PHOENIX-GC: intraperitoneal plus intravenous paclitaxel with S-1 versus standard chemotherapy in gastric cancer with peritoneal metastasis (Journal of Clinical Oncology 2018)","url":"https://doi.org/10.1200/JCO.2018.77.8613"}],"tags":[],"related":[],"cancers":["gastric"],"sections":[],"technologies":["hipec"],"targets":[],"drugs":["paclitaxel","satricabtagene-autoleucel"],"companies":[],"institutions":[],"pathways":[],"terms":["peritoneal-metastasis"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-ishigami-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Adding intraperitoneal paclitaxel to systemic chemotherapy-immunotherapy improves OS in patients with peritoneal-only metastases.","rationale":"Pharmacokinetic advantage of intraperitoneal delivery; peritoneal-only disease is a distinct, chemoresistant compartment.","test":"Randomised phase 3 restricted to peritoneal-only disease by laparoscopy; OS primary.","maturity":"early-clinical"},{"id":"idea-moon-neoantigen-vaccines-at-scale","kind":"idea","name":"Personalised cancer vaccines at commodity cost through fully automated manufacturing","aka":[],"tldr":"Vaccines tailored to each patient's tumour mutations are showing real benefit but cost a fortune to make. Automate the whole process so a personalised vaccine costs about as much as a course of chemotherapy.","summary":"Individualised neoantigen mRNA vaccines have shown reduced recurrence in melanoma with pembrolizumab (phase 2b, with phase 3 ongoing) and immune responses in pancreatic cancer, but require bespoke sequencing, epitope selection and GMP manufacture per patient at very high cost. The proposal is an engineering programme for end-to-end automation: standardised sample-to-sequence pipelines, validated epitope prediction, continuous-flow mRNA synthesis and formulation in closed robotic units sited regionally, and regulatory acceptance of platform-based release testing, targeting a manufactured cost under a few thousand dollars and turnaround under three weeks.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Prices and value): Prasad, De Jesús & Mailankody, The high price of anticancer drugs: origins, implications, barriers, solutions (Nat Rev Clin Oncol 2017)","url":"https://doi.org/10.1038/nrclinonc.2017.31"}],"tags":[],"related":[],"cancers":["melanoma","pancreatic"],"sections":[],"technologies":["neoantigen-mrna-vaccine"],"targets":[],"drugs":["intismeran-autogene","autogene-cevumeran"],"companies":["moderna","biontech"],"institutions":[],"pathways":[],"terms":["neoantigen"],"trials":[],"people":[],"bottlenecks":["b-drug-pricing","b-immunotherapy-response","b-dormancy-mrd"],"keyPapers":["paper-prasad-nat-rev-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Automated regional manufacturing reduces per-patient vaccine cost by over 90% and turnaround to under three weeks without loss of immunogenicity, making adjuvant personalised vaccination affordable for common cancers if phase 3 trials confirm efficacy.","rationale":"The science of neoantigen vaccination is maturing; if it works, access will be decided by manufacturing cost. The COVID-19 mRNA scale-up showed the platform can be industrialised.","test":"Build one automated regional unit and demonstrate cost, turnaround and product equivalence against conventional manufacture in an ongoing adjuvant vaccine trial.","maturity":"early-clinical","actor":"industry","cost":"large","horizonYears":6},{"id":"idea-prev-fit-risk-adapted-thresholds","kind":"idea","name":"Personalised stool-test cut-offs by age, sex and prior results","aka":[],"tldr":"Bowel screening uses one blood-in-stool threshold for everyone. Setting it by age, sex and the person's previous results would find more cancers with the same number of colonoscopies.","summary":"Bowel screening applies one blood-in-stool threshold to everyone, so this idea sets FIT cut-offs and intervals by age, sex and prior results: people with low prior FIT move to three-yearly screening and those with high sub-threshold values are recalled in a year. FIT haemoglobin concentration and previous FIT values strongly predict future advanced neoplasia, and colonoscopy capacity rather than FIT cost is the binding constraint, so risk adaptation should find more cancers with the same number of colonoscopies. The test is a randomised evaluation within a national programme such as the Netherlands with a four-year endpoint. At early-clinical maturity it addresses the bottlenecks The hardest cancers are found late and Overdiagnosis and false alarms.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The hardest cancers are found late): Crosby et al., Early detection of cancer (Science 2022)","url":"https://doi.org/10.1126/science.aay9040"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":["early-detection"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-early-detection","b-overdiagnosis"],"keyPapers":["paper-crosby-science"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Risk-adapted FIT increases advanced neoplasia detected per colonoscopy by at least 20% and reduces interval cancers by at least 15% at constant colonoscopy capacity.","rationale":"Colonoscopy capacity, not FIT cost, is the binding constraint; modelling from the Dutch and Scottish programmes supports it.","test":"Randomised evaluation within a national programme (e.g. the Netherlands) with a four-year endpoint.","maturity":"early-clinical","actor":"policy","cost":"small","horizonYears":4},{"id":"idea-bio2-mrd-triggered-neoantigen-vaccine","kind":"idea","name":"Personalised vaccines given only when the blood test turns positive","aka":[],"tldr":"Individualised mRNA cancer vaccines take weeks to manufacture and work best against minimal residual disease. Making the vaccine at surgery and giving it only when a blood tumour DNA test turns positive matches both facts and concentrates the cost on the minority who will relapse.","summary":"An individualised mRNA neoantigen vaccine produced immune responses and prolonged recurrence-free survival in a randomised phase 2 in ctDNA-positive resected pancreatic and colorectal cohorts, and adjuvant melanoma data support the setting. Manufacturing time is the practical constraint, which a manufacture-at-surgery, deploy-on-ctDNA-positivity design resolves, and it concentrates cost on the minority who will relapse.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Dormant cells and minimal residual disease): Tie et al., ctDNA analysis guiding adjuvant therapy in stage II colon cancer (NEJM 2022)","url":"https://doi.org/10.1056/NEJMoa2200075"}],"tags":[],"related":[],"cancers":["pancreatic","colorectal","melanoma"],"sections":[],"technologies":["neoantigen-mrna-vaccine","mrd-testing"],"targets":[],"drugs":["autogene-cevumeran","intismeran-autogene"],"companies":["biontech","moderna"],"institutions":[],"pathways":[],"terms":["neoantigen","mrd"],"trials":[],"people":[],"bottlenecks":["b-dormancy-mrd","b-drug-pricing","b-manufacturing-cell-therapy"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Vaccine manufactured at surgery and administered on first ctDNA positivity produces higher ctDNA clearance and longer relapse-free survival than vaccination of all resected patients, at a third of the cost per patient treated.","rationale":"Vaccine efficacy depends on low antigen burden and an intact immune system, both of which hold at the moment of molecular relapse. Deferring administration also avoids vaccinating the majority who are already cured.","test":"A three-arm randomised trial: vaccinate all, vaccinate on ctDNA positivity, or observe with standard care; endpoints are relapse-free survival, ctDNA clearance and cost per relapse prevented.","maturity":"early-clinical","actor":"industry","cost":"large","horizonYears":6},{"id":"idea-bio1-comparative-oncology-dogs","kind":"idea","name":"Pet dogs with spontaneous cancer as a bridge before human trials","aka":[],"tldr":"Dogs get cancers that closely resemble human ones, with real immune systems and years of natural history. Treating them, with owner consent, can test drugs in a way mice cannot.","summary":"Comparative oncology trials in client-owned dogs with spontaneous osteosarcoma, lymphoma, bladder cancer and glioma provide outbred, immunocompetent, spontaneously arising tumours with intact microenvironments. The NCI Comparative Oncology Trials Consortium has run such studies and informed human dosing for several agents. Capacity, standardisation and regulatory recognition, rather than concept, limit its use.","asOf":"2026-09-08","links":[{"label":"NCI Comparative Oncology Program","url":"https://ccr.cancer.gov/comparative-oncology-program"}],"tags":[],"related":[],"cancers":["sarcoma","glioblastoma","dlbcl"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["nci"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-preclinical-models","b-translational-valley"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Agents tested in a standardised canine trial before human phase 1 show better prediction of dose-limiting toxicity and biological activity than mouse data alone, reducing early clinical failures.","rationale":"Spontaneous canine tumours share genomics and metastatic behaviour with human counterparts and progress on a compressed timescale, giving survival readouts within one to two years.","test":"Run parallel canine and murine studies for five agents entering human development and compare which better predicted human toxicity and pharmacodynamics.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":5},{"id":"idea-acc-pharmacist-interaction-review-oral-anticancer","kind":"idea","name":"Pharmacist interaction check before every oral cancer-drug prescription","aka":[],"tldr":"Oral kinase inhibitors, CDK4/6 inhibitors and hormonal agents interact with proton pump inhibitors, anticoagulants, statins and antiarrhythmics, and are increasingly prescribed to older patients taking all of them. A mandatory oncology pharmacist review at initiation, dose change and refill, with a structured monitoring plan, would catch these interactions systematically.","summary":"Oral kinase inhibitors, CDK4/6 inhibitors, and hormonal agents have clinically significant interactions with proton pump inhibitors, anticoagulants, statins, and antiarrhythmics, and are increasingly prescribed to older multimorbid patients. Studies find potential interactions in a large proportion of such patients. A mandatory oncology pharmacist review at initiation and dose change, with a structured monitoring plan, would catch these systematically.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Older and multimorbid patients are excluded and undertreated): Mohile et al., Evaluation of geriatric assessment and management on toxic effects of cancer treatment (GAP70+, Lancet 2021)","url":"https://doi.org/10.1016/S0140-6736(21)01789-X"}],"tags":[],"related":["idea-acc-structured-deprescribing-at-diagnosis"],"cancers":[],"sections":[],"technologies":["kinase-inhibitors","cdk46-inhibitor"],"targets":[],"drugs":["palbociclib","osimertinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-aging-comorbidity","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Mandatory pharmacist review will reduce clinically significant drug interactions at initiation by at least 70% and reduce interaction-related adverse events and dose interruptions.","rationale":"Pharmacist review is the established safeguard for intravenous chemotherapy; oral agents escaped it because they are dispensed like ordinary prescriptions.","test":"A before-and-after study across five centres with interaction rates, adverse events, and dose interruptions as endpoints.","maturity":"early-clinical","actor":"clinic","cost":"small","horizonYears":1},{"id":"idea-moon-mucositis-taste-programme","kind":"idea","name":"Photobiomodulation and a taste and swallowing programme for mouth and throat toxicity","aka":[],"tldr":"Mouth ulcers and loss of taste from chemo and radiotherapy stop people eating. Low-level light therapy and structured swallowing and taste rehabilitation can help; make them standard.","summary":"Oral mucositis affects most patients receiving head and neck radiotherapy and many on intensive chemotherapy; photobiomodulation (low-level laser) is recommended by MASCC/ISOO for prevention in defined settings but is rarely available. Taste alteration and dysphagia are under-treated and drive malnutrition. The proposal is a bundled programme: photobiomodulation in eligible patients, prophylactic swallowing exercises, dietetic taste rehabilitation, and standard PRO measurement, implemented in radiotherapy and transplant units.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Toxicity and quality of life are undervalued): Di Maio et al., Symptomatic toxicities experienced during anticancer treatment: agreement between patient and physician reporting (JCO 2015)","url":"https://doi.org/10.1200/JCO.2014.57.9334"}],"tags":[],"related":[],"cancers":["head-and-neck"],"sections":[],"technologies":["imrt-igrt","photobiomodulation-mucositis"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol"],"keyPapers":["paper-di-maio-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"The bundle reduces severe mucositis by a third, reduces feeding tube dependence at six months, and improves weight maintenance during head and neck radiotherapy.","rationale":"Each component has randomised support; delivery as a bundle with measurement is the missing piece.","test":"Cluster-randomised implementation across radiotherapy units; primary endpoint severe mucositis incidence and feeding tube dependence at six months.","maturity":"early-clinical","actor":"research","cost":"small","horizonYears":3},{"id":"idea-photoimmunotherapy-plus-pd1","kind":"idea","name":"Photoimmunotherapy as an in situ vaccine with PD-1 blockade","aka":[],"tldr":"Bursting tumour cells with light releases their contents to the immune system; adding immunotherapy might turn a local treatment into a body-wide one.","summary":"The idea is to pair photoimmunotherapy with cetuximab sarotalocan and pembrolizumab in recurrent or metastatic head and neck squamous cell carcinoma, turning a local light-activated treatment into an in situ vaccine. Rapid necrotic-type death releases tumour antigens and danger signals while leaving immune cells intact, EGFR targeting spares dendritic cells, and animal models show abscopal responses with checkpoint blockade. The hypothesis is that illuminated lesions plus pembrolizumab produce responses in non-illuminated lesions more often than pembrolizumab alone; a phase 2 has already been run in the US. The test is a randomised phase 2 in patients with an illuminable and a distant lesion, with distant-lesion response as endpoint; it addresses the cold-tumour bottleneck.","asOf":"2026-09-07","links":[{"label":"Mitsunaga et al., Cancer cell-selective in vivo near-infrared photoimmunotherapy (Nature Medicine 2011)","url":"https://doi.org/10.1038/nm.2554"}],"tags":[],"related":[],"cancers":["head-and-neck"],"sections":[],"technologies":["photoimmunotherapy","checkpoint-inhibitor"],"targets":[],"drugs":["cetuximab-sarotalocan","pembrolizumab"],"companies":[],"institutions":[],"pathways":[],"terms":["abscopal-effect","immunogenic-cell-death"],"trials":["keynote-048","keynote-412","keynote-689","nct06699212","nct07276399"],"people":[],"bottlenecks":[],"keyPapers":["paper-mitsunaga-nat-med","paper-keynote-048-lancet-2019","paper-jean-pascal-machiels-lancet-2019","paper-pembrolizumab-head-and-neck-j-clin-oncol-2017"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Photoimmunotherapy of accessible lesions plus pembrolizumab produces responses in non-illuminated lesions at a higher rate than pembrolizumab alone.","rationale":"Rapid necrotic-type death releases antigens and DAMPs while leaving immune cells intact; EGFR-targeting spares dendritic cells.","test":"Randomised phase 2 in recurrent/metastatic HNSCC with ≥1 illuminable and ≥1 distant lesion; endpoint distant-lesion response.","maturity":"early-clinical"},{"id":"idea-bio1-model-patient-matching","kind":"idea","name":"Pick the laboratory model that matches the patient, not the one to hand","aka":[],"tldr":"Labs usually use whichever tumour models they already have. A searchable index that finds the model closest to a specific patient's tumour would make experiments more relevant.","summary":"Thousands of characterised models exist across DepMap, the Human Cancer Models Initiative, PDX repositories and institutional banks, but selection is driven by availability and habit. A matching engine indexing molecular profiles, ancestry, treatment history and microenvironment features would return the closest available models for a given tumour profile, and quantify how much of the clinical population has any representative model at all.","asOf":"2026-09-08","links":[{"label":"DepMap portal","url":"https://depmap.org/portal/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["organoids","pdx-models","cgp"],"targets":[],"drugs":[],"companies":[],"institutions":["broad-institute","nci"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-preclinical-models","b-trial-diversity","b-data-silos"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Formal matching shows that a substantial share of common tumour molecular subtypes and non-European ancestries have no closely matched model, and directs derivation effort toward those gaps.","rationale":"Model collections over-represent easily grown, historically sampled tumours from a narrow population, which is a plausible and testable contributor to translational failure and to inequitable drug performance.","test":"Build the index across public repositories, compute coverage of clinical genomic cohorts by subtype and ancestry, and publish the gap map as a derivation priority list.","maturity":"speculative","actor":"data","cost":"small","horizonYears":2},{"id":"idea-bio2-radiotherapy-sting-fractionation","kind":"idea","name":"Pick the radiation dose that switches the immune alarm on, not off","aka":[],"tldr":"Radiation can alert the immune system through the cGAS-STING pathway, but single doses above roughly 12 to 18 Gy switch on the enzyme TREX1, which destroys the alarm signal. Choosing fractionated schedules around 8 Gy times three for immune priming may add benefit at no extra cost.","summary":"Single fractions above roughly 12-18 Gy induce the DNA exonuclease TREX1, which degrades cytoplasmic DNA and prevents cGAS-STING activation, whereas fractionated schedules around 8 Gy times three maximise interferon signalling in mouse models. Radiotherapy plus immunotherapy trials have used dose and fractionation chosen for tumour control or convenience, not for immune priming, which may explain inconsistent abscopal results.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Cold tumours and the immunosuppressive microenvironment): Haslam & Prasad, Estimation of the percentage of US patients eligible for and responding to checkpoint inhibitors (JAMA Netw Open 2019)","url":"https://doi.org/10.1001/jamanetworkopen.2019.2535"}],"tags":[],"related":["radiation-plus-io"],"cancers":[],"sections":[],"technologies":["sbrt","checkpoint-inhibitor","flash-rt"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["cgas-sting"],"terms":["abscopal-effect","immunogenic-cell-death"],"trials":[],"people":[],"bottlenecks":["b-tme-immunosuppression","b-surgery-radiation-innovation","b-immunotherapy-response"],"keyPapers":["paper-haslam-jama-netw-open"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Immune-optimised fractionation produces higher intratumoural interferon signatures and more abscopal responses than a single high-dose fraction in patients receiving concurrent checkpoint blockade, at equal local control.","rationale":"The TREX1 threshold effect is one of the few quantitative dose-response rules in immuno-radiobiology, and it is directly testable in humans with biopsy transcriptomics. Radiotherapy schedules cost nothing to change.","test":"A randomised biomarker trial of single high-dose versus immune-optimised fractionation to an index lesion with concurrent checkpoint blockade; primary endpoint the interferon-stimulated gene signature in a non-irradiated lesion.","maturity":"preclinical-evidence","actor":"clinic","cost":"medium","horizonYears":5},{"id":"idea-tr1-lmic-sites-in-pivotal-trials","kind":"idea","name":"Pivotal trials include sites in Africa, South Asia and Latin America, sponsor-funded","aka":[],"tldr":"Most of the world's cancer patients live in countries that host almost no registrational trials. Including sites there, and paying to build them up, would make results apply globally and speed local access.","summary":"Regulators and funders expect global pivotal trials to include a minimum share of sites in low- and middle-income countries, with sponsors funding site capacity (training, pharmacy, imaging, data systems) that persists after the trial. Post-trial access to the drug in participating countries is a condition. Latin American and Indian networks have demonstrated high-quality accrual; African oncology trial infrastructure is the least developed and would be prioritised.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Trials do not represent the people who get cancer): Loree et al., Disparity of race reporting and representation in trials leading to cancer drug approvals (JAMA Oncology 2019)","url":"https://doi.org/10.1001/jamaoncol.2019.1870"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["tata-memorial","iarc"],"pathways":[],"terms":[],"trials":[],"people":["barrios-carlos","gupta-sudeep","ilbawi-andre"],"bottlenecks":["b-trial-diversity","b-global-access"],"keyPapers":["paper-loree-jama-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Trials with LMIC sites will enrol faster overall, will produce efficacy and safety data generalisable to those populations, and drugs will be registered and reimbursed in participating countries sooner than in comparable non-participating countries.","rationale":"HIV and malaria trials built durable research infrastructure in Africa; oncology has not. Regulatory approval in LMICs often lags years partly because there is no local data.","test":"Track time to local registration and pricing agreements for drugs whose pivotal trials included LMIC sites versus those that did not, adjusting for company and indication.","maturity":"early-clinical","actor":"industry","cost":"large","horizonYears":5},{"id":"idea-moon-results-back-to-participants","kind":"idea","name":"Plain-language trial results returned to every participant within a year","aka":[],"tldr":"If you join a cancer trial you should be told what it found, in plain words, within twelve months of the results, including if the treatment did not work.","summary":"Most trial participants never learn the results. The EU Clinical Trials Regulation requires lay summaries; enforcement and quality are patchy, and most other jurisdictions have no requirement. The proposal is a global norm: lay summary within 12 months of primary completion, delivered directly to participants, with negative results treated identically, and posting in registries as a condition of publication.","asOf":"2026-09-08","links":[{"label":"ClinicalTrials.gov","url":"https://clinicaltrials.gov/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-patient-voice","b-negative-results"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Returning results increases willingness to enrol in future trials among participants and their networks and increases timely reporting of negative trials.","rationale":"Reciprocity is the moral basis of research participation; participants who receive results are more likely to recommend trials, and the requirement creates a deadline that also forces disclosure of negative findings.","test":"Compare enrolment attitudes and re-participation in cohorts who did and did not receive summaries; audit registry completeness where the rule is enforced versus not.","maturity":"being-tested-at-scale","actor":"regulator","cost":"small","horizonYears":2},{"id":"idea-bio1-adaptive-car-antigen-switch","kind":"idea","name":"Plan the second CAR-T target before the first one is lost","aka":[],"tldr":"Cell therapies fail when the tumour stops showing the marker they were built to find. Preparing an alternative product in advance would let doctors switch quickly.","summary":"Antigen-negative relapse accounts for a substantial share of CAR-T failures in B-cell malignancies and is emerging in multiple myeloma. Strategies include dual-target and tandem CARs, sequential products, and adaptor or universal CAR platforms whose specificity is set by a separately dosed molecule. A pragmatic programme would monitor antigen density after infusion and have the alternative product manufactured or an adaptor available before relapse.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Acquired resistance to every therapy): Soria et al., Osimertinib in untreated EGFR-mutated NSCLC (FLAURA, NEJM 2018)","url":"https://doi.org/10.1056/NEJMoa1713137"}],"tags":[],"related":[],"cancers":["dlbcl","multiple-myeloma","all-leukemia"],"sections":[],"technologies":["car-t","allogeneic-cell-therapy","mrd-testing"],"targets":["cd19","cd20","bcma","gprc5d"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["mrd"],"trials":[],"people":[],"bottlenecks":["b-resistance","b-manufacturing-cell-therapy"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Pre-planned antigen switching, triggered by falling antigen density or early molecular relapse rather than by overt relapse, improves durable remission rates compared with reactive switching at relapse.","rationale":"Antigen loss is detectable before clinical relapse using flow cytometry and MRD assays; the delay in manufacturing a second product is usually what makes switching too late.","test":"Single-arm study of antigen-density and MRD-triggered pre-emptive switching in relapsed B-cell malignancy, with durable remission at two years compared with historical reactive management.","maturity":"early-clinical","actor":"clinic","cost":"medium","horizonYears":5},{"id":"idea-reg-adc-platform-designation","kind":"idea","name":"Platform designation for ADC linker-payloads so manufacturing data carry across","aka":[],"tldr":"Antibody-drug conjugates built on the same linker and payload, such as deruxtecan or vedotin, share the same conjugation process, payload synthesis, impurity profile and much of the toxicology. FDA, EMA and PMDA should designate these linker-payloads as platforms so a new ADC files only antibody-specific manufacturing and toxicology data.","summary":"FDA's platform technology designation programme (draft guidance 2024, from the 2022 omnibus legislation) allows a well-characterised technology used in an approved product to be referenced in later applications. ADC linker-payloads (deruxtecan, vedotin, site-specific enzymatic conjugation from Synaffix or Araris) are natural platforms: the conjugation process, payload synthesis, impurity profile and much of the non-clinical toxicology are antibody-independent. The proposal is for FDA, EMA and PMDA to jointly designate ADC linker-payload platforms and publish what data may be referenced, so a new ADC on a designated platform files only antibody-specific CMC and toxicology.","asOf":"2026-09-08","links":[{"label":"FDA platform technology designation","url":"https://www.fda.gov/regulatory-information/search-fda-guidance-documents/platform-technology-designation-program-drug-development"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["adc","site-specific-conjugation"],"targets":[],"drugs":[],"companies":["daiichi-sankyo","synaffix","araris"],"institutions":[],"pathways":[],"terms":["linker","payload"],"trials":[],"people":[],"bottlenecks":["b-manufacturing-cell-therapy","b-regulatory-fragmentation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"ADCs filed on a designated platform reach IND with at least 40% less non-clinical and CMC work and show no higher rate of clinical holds or manufacturing-related deficiencies than conventionally filed ADCs.","rationale":"Deruxtecan has now been carried by many antibodies with a consistent payload toxicity profile; repeating payload characterisation per product adds cost without information. Platform reuse is how vaccines and gene therapy vectors are increasingly regulated.","test":"Designate two or three linker-payload platforms in a pilot, track IND timelines and deficiency letters for products using them against matched ADCs, and publish the outcomes.","maturity":"early-clinical","actor":"regulator","cost":"small","horizonYears":3},{"id":"idea-data-point-of-care-randomisation","kind":"idea","name":"Point-of-care randomisation built into the oncology record","aka":[],"tldr":"When two accepted treatments are equally reasonable, the computer system would offer to randomise the choice and track the result, turning ordinary care into a continuous trial.","summary":"Learning health systems embed randomisation into workflow where genuine equipoise exists (dose schedules, supportive care, sequencing). The US Veterans Affairs system and the NHS have run point-of-care trials; oncology has few. The proposal builds a reusable EHR module (consent, randomisation, outcome capture via registry linkage) so that any cancer network can run a low-cost comparative effectiveness trial in weeks.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Data silos): AACR Project GENIE","url":"https://www.aacr.org/professionals/research/aacr-project-genie/"}],"tags":[],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["real-world-evidence"],"trials":[],"people":[],"bottlenecks":["b-data-silos","b-trial-design","b-trial-enrolment"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Embedded randomisation will enrol more than ten times as many patients per year as conventional comparative effectiveness trials at less than a tenth of the per-patient cost.","rationale":"Registry-based randomised trials in cardiology (TASTE, SWEDEHEART) enrolled thousands at roughly 50 dollars per patient; the design transfers to questions with routine outcomes.","test":"Run one embedded trial (for example, two accepted anti-emetic regimens or two follow-up imaging schedules) in one network; measure enrolment rate, cost and completeness of outcome capture.","maturity":"early-clinical","actor":"clinic","cost":"medium","horizonYears":3},{"id":"idea-bio2-io-biomarker-data-commons","kind":"idea","name":"Pool every immunotherapy trial's biomarker data into one commons","aka":[],"tldr":"Dozens of trials have collected immune, genomic and imaging data on the same drugs. Nobody can analyse them together, so the answer stays hidden in fragments.","summary":"Predicting checkpoint response is a small-data problem imposed by fragmentation, not by biology: individual trials have hundreds of patients, while the aggregate is tens of thousands with multimodal data. A federated commons with harmonised data models, standardised endpoints and privacy-preserving analysis, backed by a condition of funding or of approval, would allow multimodal models to be trained and, importantly, externally validated.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (No one can predict who responds to immunotherapy): Haslam & Prasad (JAMA Network Open 2019)","url":"https://doi.org/10.1001/jamanetworkopen.2019.2535"}],"tags":[],"related":["idea-multimodal-foundation-model","cbioportal","genie","clinicaltrials-gov","oncokb"],"cancers":[],"sections":[],"technologies":["single-cell-spatial","pathology-foundation-model","rna-seq"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["tmb","tps","real-world-evidence"],"trials":[],"people":[],"bottlenecks":["b-immunotherapy-response","b-data-silos","b-ai-validation"],"keyPapers":["paper-haslam-jama-netw-open"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A pooled multimodal dataset of more than 10,000 checkpoint-treated patients yields a validated predictor that outperforms PD-L1 and tumour mutational burden by a clinically meaningful margin in prospective use.","rationale":"Every previous jump in biological prediction followed data aggregation rather than method novelty, from genome-wide association studies to protein structure prediction. Existing single-trial models fail external validation, which is the signature of insufficient training diversity.","test":"Start with three sponsors and two academic consortia contributing harmonised data for one tumour type, and publish an externally validated model plus the harmonisation standard itself.","maturity":"speculative","actor":"data","cost":"medium","horizonYears":5},{"id":"idea-bio1-federated-evolution-atlas","kind":"idea","name":"Pool every multi-sample tumour genome into one open evolution atlas","aka":[],"tldr":"Several big projects have sequenced the same tumours at different times and places, but their data sit apart. Bringing them together with common analysis would show general rules of how cancers evolve.","summary":"TRACERx, PEACE, Hartwig, PCAWG and dozens of institutional cohorts hold multi-region or longitudinal genomes with treatment history, each analysed with different phylogeny tools. A federated atlas with a common clonal-reconstruction pipeline, harmonised treatment annotations and an open query interface would allow questions such as which drivers are always truncal, which resistance routes are convergent, and how fast clones expand under each drug.","asOf":"2026-09-08","links":[{"label":"Hartwig Medical Foundation","url":"https://www.hartwigmedicalfoundation.nl/en/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["wes-wgs"],"targets":[],"drugs":[],"companies":[],"institutions":["francis-crick","cruk","broad-institute"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-tumor-heterogeneity","b-data-silos"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Harmonised analysis of over 5,000 multi-sample cases identifies at least five recurrent, treatment-specific evolutionary rules that individual cohorts lacked the power to detect and that predict outcome in held-out data.","rationale":"Single-timepoint atlases (TCGA, GENIE) changed the field; the longitudinal equivalent does not exist. Federated analysis avoids the consent and jurisdiction barriers of pooling raw data.","test":"Fund a two-year harmonisation effort across five consortia with a common pipeline; deliverable is a public query portal and a first analysis paper with pre-registered hypotheses.","maturity":"preclinical-evidence","actor":"data","cost":"medium","horizonYears":3},{"id":"idea-cost-pooled-procurement-essential","kind":"idea","name":"Pool purchasing of essential cancer medicines across countries","aka":[],"tldr":"Small countries pay more for the same generic chemotherapy because they buy alone; the PAHO Strategic Fund and the WHO essential medicines list show that buying together brings prices down and keeps supply steady.","summary":"The WHO Model List of Essential Medicines (24th list, 2025) includes a core set of cancer medicines. The PAHO Strategic Fund is a regional pooled-procurement mechanism for essential medicines that member states can use; the Global Platform for Access to Childhood Cancer Medicines (WHO and St. Jude) applies the model to paediatric oncology. Extending pooled procurement to the adult essential-medicines set (platinums, taxanes, anthracyclines, imatinib, tamoxifen, letrozole, trastuzumab biosimilars) would give middle-income countries the prices large buyers get and reduce shortages.","asOf":"2026-09-10","links":[{"label":"WHO Model Lists of Essential Medicines","url":"https://www.who.int/groups/expert-committee-on-selection-and-use-of-essential-medicines/essential-medicines-lists"},{"label":"PAHO Strategic Fund","url":"https://www.paho.org/en/paho-strategic-fund"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":["imatinib","tamoxifen","letrozole","cisplatin","paclitaxel"],"companies":[],"institutions":["who","st-jude"],"pathways":[],"terms":["who-essential-medicines"],"trials":[],"people":[],"bottlenecks":["b-global-access","b-drug-pricing"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Pooled regional procurement of the WHO essential cancer medicines will reduce unit prices for participating countries by more than a quarter and cut stock-outs by half within three years.","rationale":"Pooled procurement has worked for vaccines, antiretrovirals and tuberculosis drugs; cancer generics have the same economics.","test":"PAHO or a regional body publishes prices paid and stock-out data for participating versus non-participating countries.","maturity":"being-tested-at-scale","actor":"policy","cost":"medium","horizonYears":3},{"id":"idea-fund-proton-coverage-with-evidence","kind":"idea","name":"Pooled coverage-with-evidence for proton therapy across all centres","aka":[],"tldr":"Proton therapy costs far more than standard radiotherapy and, for most adult cancers, nobody knows whether it is better. Payers would cover it only inside trials or registries that answer that question, across every centre at once.","summary":"National payers and proton centres agree that reimbursement for adult indications without established benefit is conditional on enrolment in pragmatic randomised trials (proton versus photon) or, where randomisation is unacceptable, in a common prospective registry with matched photon comparators, pooled internationally. Existing trials (PARTIQoL in prostate, RADCOMP in breast, NRG lung and oesophageal trials) have struggled with accrual partly because patients can obtain protons outside trials. Pooling and conditioning payment fixes accrual and produces evidence proportionate to the investment already made in dozens of centres.","asOf":"2026-09-08","links":[{"label":"PARTIQoL (NCT01617161)","url":"https://clinicaltrials.gov/study/NCT01617161"},{"label":"RADCOMP (NCT02603341)","url":"https://clinicaltrials.gov/study/NCT02603341"}],"tags":[],"related":["idea-fund-flash-evidence-programme","idea-fund-adaptive-radiotherapy-evidence","idea-bio2-let-rbe-ab-selects-protons","proton-vs-imrt"],"cancers":["prostate","breast-hr-positive","esophageal"],"sections":[],"technologies":["proton-therapy","carbon-ion","imrt-igrt"],"targets":[],"drugs":[],"companies":["iba","mevion"],"institutions":[],"pathways":[],"terms":["relative-biological-effectiveness","linear-energy-transfer","alpha-beta-ratio"],"trials":["partiqol","radcomp"],"people":["juergen-debus"],"bottlenecks":["b-surgery-radiation-innovation","b-drug-pricing"],"keyPapers":["paper-partiqol-astro-2024"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Coverage-with-evidence conditions triple accrual to randomised proton versus photon trials within three years and produce definitive comparative results in at least three common adult indications within six.","rationale":"The Netherlands' model-based indication protocol and coverage-with-evidence in several US insurers show payers can condition access; the proton field itself has called for randomised evidence for two decades and has produced little because the incentives run the other way.","test":"Implement the condition across a payer coalition for two adult indications and compare trial accrual rates and time to completion with the period before.","maturity":"being-tested-at-scale","actor":"payer","cost":"large","horizonYears":5},{"id":"idea-reg-pooled-procurement-adult-essentials","kind":"idea","name":"Pooled international procurement of essential adult cancer medicines","aka":[],"tldr":"Countries buying cancer drugs alone pay more and face shortages. Buying together, as they already do for childhood cancer drugs and vaccines, cuts prices and secures supply.","summary":"The WHO and St Jude Global Platform for Access to Childhood Cancer Medicines (2021) pools demand across countries for paediatric essential medicines; PAHO's Strategic Fund and Gavi do the same for other products. Adult essential oncology medicines on the WHO Model List (cisplatin, carboplatin, paclitaxel, docetaxel, tamoxifen, letrozole, imatinib, trastuzumab biosimilars and others) are procured nationally at widely varying prices. The proposal is a pooled procurement mechanism for these products covering low- and lower-middle-income countries, with multi-year volume guarantees, quality prequalification and a buffer stock against shortages.","asOf":"2026-09-08","links":[{"label":"WHO Global Platform for Access to Childhood Cancer Medicines (page moved; nearest live section)","url":"https://www.who.int/initiatives/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":["carboplatin","paclitaxel","imatinib","trastuzumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-drug-pricing","b-global-access"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Pooled procurement reduces the median price paid for essential adult oncology medicines by participating countries by at least 40% and reduces reported stock-outs by half within three years.","rationale":"Fragmented small tenders are the main reason LMICs pay more than high-income countries for the same generic; pooled volume and predictable demand are what generic manufacturers need to offer low prices and reliable supply.","test":"Launch the pool for ten adult essential medicines in 15 countries and compare procurement prices and stock-out reports with the countries' own prior tenders and with non-participating peers.","maturity":"being-tested-at-scale","actor":"policy","cost":"large","horizonYears":3},{"id":"idea-moon-pooled-procurement-licensing-pool","kind":"idea","name":"Pooled procurement and voluntary licensing for essential cancer medicines in low-income countries","aka":[],"tldr":"Buy essential cancer drugs for many countries at once and license newer ones to generic makers, as was done for HIV, so prices fall to what those health systems can pay.","summary":"HIV treatment reached tens of millions because the Medicines Patent Pool, pooled procurement and tiered pricing lowered costs by over 90%. Cancer has partial efforts (the ATOM Coalition, pooled tenders for childhood cancer drugs) but no comprehensive mechanism. The proposal is a cancer medicines pool: voluntary licences from originators for defined territories on a core list (trastuzumab, imatinib, pembrolizumab or biosimilar checkpoint inhibitors, and generics with supply problems), pooled multi-country tenders, quality assurance and supply security, financed with development bank guarantees.","asOf":"2026-09-08","links":[{"label":"Medicines Patent Pool","url":"https://medicinespatentpool.org/"},{"label":"WHO Model List of Essential Medicines","url":"https://list.essentialmeds.org/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":["trastuzumab","imatinib","pembrolizumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-global-access","b-drug-pricing"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Pooled licensing and procurement cut prices of listed medicines by over 70% in participating countries and increase the treated fraction of eligible patients severalfold within five years.","rationale":"Volume, predictability and competition among licensed manufacturers are what drove HIV prices down; the same levers are available for cancer biologics and small molecules.","test":"Pilot pooled procurement of five essential medicines across ten countries; measure price, availability and treatment rates against baseline.","maturity":"early-clinical","actor":"policy","cost":"large","horizonYears":4},{"id":"idea-moon-population-germline-screening","kind":"idea","name":"Population germline screening for hereditary cancer genes with cascade testing","aka":[],"tldr":"Most people carrying a high-risk cancer gene do not know it until someone in the family gets cancer. Offer testing to all adults so carriers can be protected before that happens.","summary":"Family-history-based testing misses about half of BRCA and Lynch carriers. Population screening pilots (Ashkenazi BRCA programmes, Geisinger MyCode, Healthy Nevada) identify carriers efficiently and studies suggest cost-effectiveness at current sequencing prices. The proposal is national population screening for a defined panel of actionable hereditary cancer genes offered to all adults at a set age, with automated cascade testing offers to relatives, standardised risk-reducing pathways (enhanced surveillance, chemoprevention, risk-reducing surgery) and long-term outcome tracking.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Inherited risk is mostly unidentified): Childers et al., National estimates of genetic testing in women with breast or ovarian cancer (JCO 2017)","url":"https://doi.org/10.1200/JCO.2017.73.6314"}],"tags":[],"related":[],"cancers":["ovarian","colorectal","breast-hr-positive"],"sections":[],"technologies":["germline-testing","chemoprevention"],"targets":["brca"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["germline-vs-somatic"],"trials":[],"people":[],"bottlenecks":["b-hereditary-risk","b-prevention-adoption"],"keyPapers":["paper-childers-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Population screening identifies at least twice as many carriers as family-history testing and reduces incidence of advanced BRCA- and Lynch-associated cancers among carriers by half within a decade.","rationale":"Carrier identification followed by proven risk reduction prevents cancers rather than treating them, and sequencing cost is now trivial relative to a single cancer treatment.","test":"Regional programme with randomised age-cohort rollout; endpoints carrier detection rate, uptake of risk reduction and stage at diagnosis of hereditary cancers versus unscreened regions.","maturity":"being-tested-at-scale","actor":"policy","cost":"large","horizonYears":5},{"id":"idea-prev-hpv-self-sampling-mailed-default","kind":"idea","name":"Post every woman an HPV self-test kit instead of asking her to book a smear","aka":[],"tldr":"Women who never book a smear test are missed by invitation-based screening. Posting an HPV self-sampling kit as the default invitation, as the Netherlands and Australia do, reaches them, and PCR-based self-samples match clinician samples for detecting high-grade precancer.","summary":"HPV self-sampling has equivalent sensitivity to clinician-collected samples for CIN2+ with PCR-based tests. Propose opt-out mailed kits as the default invitation for all eligible women, with clinician sampling as an alternative, and triage of positives by extended genotyping or methylation to avoid unnecessary colposcopy.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Prevention we already have is not deployed): Islami et al., Proportion of cancer attributable to modifiable risk factors (CA 2018)","url":"https://doi.org/10.3322/caac.21440"}],"tags":[],"related":[],"cancers":["cervical"],"sections":["prevention","early-detection"],"technologies":["methylation-profiling"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption"],"keyPapers":["paper-islami-ca-cancer-j-clin"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Mailed default self-sampling raises screening coverage by at least 10 percentage points overall and 15 points in the most deprived quintile.","rationale":"Dutch, Australian and Swedish experience; removes clinic access barriers and embarrassment.","test":"Switch the national programme with a stepped-wedge evaluation.","maturity":"being-tested-at-scale","actor":"policy","cost":"medium","horizonYears":3},{"id":"idea-tr1-post-marketing-safety-by-ancestry-and-sex","kind":"idea","name":"Post-marketing safety monitoring stratified by ancestry and sex, with label updates","aka":[],"tldr":"Once a drug is in wide use, real-world records could be checked routinely for whether side effects differ by ancestry or sex, since trials were too small in those groups to notice. Findings would go into the label.","summary":"Regulators run active pharmacovigilance on linked EHR, claims and registry data for new oncology drugs, pre-specifying analyses of serious adverse events and discontinuation by self-reported race, genetic ancestry where available, and sex, with a defined signal threshold that triggers label review. Sentinel-type systems exist in the US and EU but rarely stratify this way.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Trials do not represent the people who get cancer): Loree et al., Disparity of race reporting and representation in trials leading to cancer drug approvals (JAMA Oncology 2019)","url":"https://doi.org/10.1001/jamaoncol.2019.1870"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["real-world-evidence","irae"],"trials":[],"people":[],"bottlenecks":["b-trial-diversity","b-real-world-evidence"],"keyPapers":["paper-loree-jama-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Stratified surveillance will detect subgroup-specific toxicity signals for several agents within three years of approval that were not visible in pivotal trials, leading to label changes.","rationale":"Under-enrolment means subgroup safety is unknown at approval; real-world use quickly generates the numbers, but only if the analysis is planned.","test":"Apply stratified surveillance to the ten most-used oncology drugs approved in the last five years and count actionable signals.","maturity":"speculative","actor":"regulator","cost":"medium","horizonYears":3},{"id":"idea-tr1-power-for-meaningful-benefit","kind":"idea","name":"Power trials to detect a benefit patients would value, not the smallest detectable one","aka":[],"tldr":"A trial can be designed to detect a tiny improvement that is statistically real but too small to matter. Protocols should state up front what size of benefit would be worth having, and be built to detect that.","summary":"Protocols pre-declare the smallest benefit patients would value, using the ESMO-MCBS or ASCO Value Framework thresholds (e.g., a hazard ratio and absolute gain in median OS or PFS), justify the sample size against it, and report whether the observed effect met it. Regulators and HTA bodies use the pre-declared threshold in review, discouraging trials sized to detect trivial differences.","asOf":"2026-09-08","links":[{"label":"ESMO Magnitude of Clinical Benefit Scale","url":"https://www.esmo.org/guidelines/esmo-mcbs"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["esmo","asco"],"pathways":[],"terms":["hazard-ratio","os","pfs"],"trials":[],"people":["nathan-cherny"],"bottlenecks":["b-trial-design","b-drug-pricing"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Requiring a pre-declared meaningful benefit will reduce the number of approvals with marginal absolute gains and will shift sample sizes and endpoints toward those that capture patient-relevant differences.","rationale":"Analyses of approved cancer drugs show many with small absolute survival gains; sample-size inflation makes trivial effects significant. Pre-declaration is the standard in non-inferiority trials and could be symmetric.","test":"Audit recent approvals against ESMO-MCBS grades; pilot pre-declaration in cooperative-group protocols and track whether the observed effects meet it.","maturity":"speculative","actor":"regulator","cost":"small","horizonYears":2},{"id":"idea-acc-pragmatic-trials-over-75-function-endpoints","kind":"idea","name":"Pragmatic trials in patients over 75 with function, not just survival, as the primary endpoint","aka":[],"tldr":"For a frail 80-year-old, staying independent may matter more than living a few months longer. Trials designed for older patients should measure what they care about.","summary":"Standard oncology endpoints do not capture what matters most to older patients: independence, cognition, and time at home. Pragmatic, embedded trials in routine care for patients over 75 with composite endpoints (survival free of functional decline, days alive and out of hospital) would produce decision-relevant evidence for the largest group of cancer patients. Cooperative groups have run a few such trials; a dedicated funding stream would create a portfolio.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Older and multimorbid patients are excluded and undertreated): Mohile et al., Evaluation of geriatric assessment and management on toxic effects of cancer treatment (GAP70+, Lancet 2021)","url":"https://doi.org/10.1016/S0140-6736(21)01789-X"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["geriatric-assessment"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-aging-comorbidity","b-trial-design","b-trial-enrolment"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Pragmatic function-endpoint trials will change treatment recommendations for at least three common indications in older patients within five years, and will enrol faster per site than conventional trials.","rationale":"Older patients accept enrolment when the questions and endpoints are relevant to them; embedding in routine care reduces the burden that excludes them.","test":"Fund a portfolio of five pragmatic trials in the over-75s across common cancers with pre-specified composite functional endpoints and monitor accrual and guideline impact.","maturity":"early-clinical","actor":"research","cost":"large","horizonYears":5},{"id":"idea-prev-mced-change-control-plan","kind":"idea","name":"Pre-agreed update rules so an MCED test is not obsolete when its trial reads out","aka":[],"tldr":"A cancer blood test improves every year, but a ten-year trial tests the old version. Regulators and sponsors could agree in advance how updates are validated and carried into the result.","summary":"FDA's Predetermined Change Control Plan for AI devices offers a model. Propose an MCED-specific plan: the classifier may be updated on banked baseline samples under locked-test-set rules, each version must be shown non-inferior on a sequestered set, and the primary analysis uses the enrolment version with a pre-specified sensitivity analysis re-scoring banked plasma.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The hardest cancers are found late): Crosby et al., Early detection of cancer (Science 2022)","url":"https://doi.org/10.1126/science.aay9040"}],"tags":[],"related":[],"cancers":[],"sections":["early-detection"],"technologies":["mced","methylation-profiling"],"targets":[],"drugs":[],"companies":["grail"],"institutions":[],"pathways":[],"terms":[],"trials":["nhs-galleri","pathfinder-2"],"people":[],"bottlenecks":["b-early-detection","b-ai-validation","b-regulatory-fragmentation"],"keyPapers":["paper-crosby-science"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"With banked plasma re-scored by an updated classifier under pre-agreed rules, estimated effect sizes fall within 10% of those from the enrolment version, allowing an updated test to inherit trial evidence.","rationale":"Without this, each improved assay restarts the evidence clock, which is why the field keeps launching new observational studies instead of finishing randomised ones.","test":"Apply retrospectively in NHS-Galleri or PATHFINDER 2 banked plasma; publish agreement between classifier versions.","maturity":"speculative","actor":"regulator","cost":"small","horizonYears":3},{"id":"idea-tr1-pre-consented-cohort-randomisation","kind":"idea","name":"Pre-consented cohorts that can be randomised to future trials (TwiCs)","aka":[],"tldr":"Patients join a long-term cohort once and agree in advance that they may be offered new treatments as they appear, while others in the cohort serve as the comparison group. No new trial has to start from zero.","summary":"The 'trials within cohorts' (TwiCs, or cohort multiple randomised controlled trial) design enrols a disease cohort with staged consent: patients agree to data collection and to being randomly selected for future interventions; those selected are offered the intervention, the rest continue standard care as controls. Utrecht's UMBRELLA breast cancer cohort has run several such trials. The idea is a cohort per major cancer in each large network.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Trials enrol too few, too slowly): Unger et al., Systematic review of barriers to cancer trial participation (JNCI 2019)","url":"https://doi.org/10.1093/jnci/djy221"}],"tags":[],"related":[],"cancers":["breast-hr-positive","prostate","colorectal"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["nki"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-enrolment","b-trial-design"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Standing TwiCs cohorts will launch new randomised comparisons with under three months from question to first randomisation and enrol controls at near-zero marginal cost, compared with 12-24 months for conventional trial start-up.","rationale":"Recruitment, consent infrastructure and outcome capture are fixed costs paid once for the cohort. The design also reduces disappointment bias in controls, who are not asked to consent to a treatment they do not receive.","test":"Fund one TwiCs cohort in a common cancer at a national network and report time to first randomisation and cost per randomised patient for the first three embedded trials.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":3},{"id":"idea-bio1-preclinical-preregistration","kind":"idea","name":"Pre-register animal efficacy studies like clinical trials","aka":[],"tldr":"Clinical trials must be registered before they start so that failures cannot be hidden. Animal studies used to justify human trials should follow the same rule.","summary":"Publication bias and flexible analysis inflate preclinical effect sizes; systematic reviews repeatedly find that animal efficacy is overstated relative to later clinical results. A registry requiring the protocol, sample size, randomisation, blinding and primary endpoint before pivotal in vivo efficacy studies, enforced by funders and journals, would make preclinical evidence auditable. The ARRIVE guidelines exist but are advisory.","asOf":"2026-09-08","links":[{"label":"ARRIVE guidelines","url":"https://arriveguidelines.org/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["nci","cruk"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-preclinical-models","b-reproducibility","b-negative-results"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Pre-registered in vivo efficacy studies report smaller average effect sizes and higher replication rates than unregistered studies, and pre-registration reduces the rate of failed phase 2 trials in programmes that relied on them.","rationale":"Registration reduced positive-result rates in clinical cardiology trials, an effect large enough to be visible; the same incentives operate preclinically with weaker safeguards.","test":"A funder mandates registration for pivotal in vivo studies in its portfolio for three years and compares effect sizes and independent replication with a matched unregistered portfolio.","maturity":"speculative","actor":"policy","cost":"small","horizonYears":4},{"id":"idea-tr2-biomarker-study-registry","kind":"idea","name":"Pre-register biomarker validation studies the way trials are registered","aka":[],"tldr":"Drug trials must be registered before they start so results cannot be hidden or reshaped. Studies that claim a biomarker predicts outcome should be registered too.","summary":"Biomarker studies suffer from selective reporting, flexible cut-points and unreported failed validations. A registry for biomarker validation studies (marker, assay, population, pre-specified analysis and cut-point, primary performance measure), required by journals for prognostic and predictive claims, would enable tracking of validation attempts including the negative ones, and reduce analytic flexibility.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Biomarkers are not validated or standardised): Fernandez et al., Examination of low ERBB2 protein expression in breast cancer tissue (JAMA Oncology 2022)","url":"https://doi.org/10.1001/jamaoncol.2021.7239"}],"tags":[],"related":["clinicaltrials-gov","idea-tr2-preclinical-registered-reports"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-biomarker-validation","b-reproducibility"],"keyPapers":["paper-fernandez-jama-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Registered biomarker studies will report smaller effect sizes on average than unregistered studies of the same markers, and the proportion of validated biomarkers that replicate will rise.","rationale":"Trial registration reduced positive reporting bias in clinical trials; the same mechanism applies to observational biomarker research, as the REMARK and TRIPOD guidelines argue.","test":"Launch the registry with two journals requiring registration; compare reported effect sizes and replication rates over three years.","maturity":"speculative","actor":"policy","cost":"small","horizonYears":2},{"id":"idea-reg-preregistered-ai-repurposing-scoring","kind":"idea","name":"Pre-registered, publicly scored AI ranking of repurposing candidates for cancer","aka":[],"tldr":"AI systems claim to find new uses for old drugs, but their predictions are rarely tested fairly. Publish their cancer predictions in advance and score them against trial results.","summary":"Knowledge-graph and language-model approaches to repurposing (Every Cure, funded by ARPA-H; academic systems such as those built on Hetionet and Open Targets) generate ranked lists of drug-disease pairs, but their forward-looking accuracy in oncology is unknown because predictions are published selectively after the fact. The proposal is a public benchmark: each participating system deposits time-stamped ranked predictions for defined cancer indications; a neutral body scores them annually against subsequent randomised trial results and target trial emulations, and the repurposing fund preferentially trials candidates on which independent systems agree.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (No incentive to repurpose cheap drugs): Pantziarka et al., The Repurposing Drugs in Oncology (ReDO) Project (ecancer 2014)","url":"https://doi.org/10.3332/ecancer.2014.442"}],"tags":[],"related":["open-targets","drugbank-chembl"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-generic-repurposing","b-ai-validation"],"keyPapers":["paper-pantziarka-ecancermedicalscience"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Candidates ranked highly by at least two independent pre-registered systems have a positive-trial rate at least twice that of candidates selected by conventional literature review.","rationale":"Prospective, pre-registered evaluation is the only way to know whether these tools add value beyond the literature they were trained on; if they do, they should direct scarce trial funding, and if they do not, that should be known.","test":"Launch the benchmark with three systems and a five-year horizon; compare the fate of top-ranked candidates with a matched set chosen by expert panel.","maturity":"early-clinical","actor":"data","cost":"small","horizonYears":4},{"id":"idea-data-observational-study-registration","kind":"idea","name":"Pre-registration and results reporting for real-world cancer studies","aka":[],"tldr":"Just as clinical trials must be registered before they start, studies using hospital data should be registered too, so the failed or unwelcome ones cannot quietly disappear.","summary":"Real-world studies are prone to selective reporting and analytic flexibility; there is no registration requirement. The proposal creates a registry for observational oncology studies (protocol, analysis plan, data source, funder) with results deposition within 12 months, required by journals, regulators considering RWE, and funders. The EU PAS register and the RWE Transparency Initiative are partial precedents.","asOf":"2026-09-08","links":[{"label":"EU PAS Register (HMA-EMA catalogue)","url":"https://catalogues.ema.europa.eu/"}],"tags":[],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["real-world-evidence"],"trials":[],"people":[],"bottlenecks":["b-real-world-evidence","b-negative-results","b-reproducibility"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Mandatory registration will make more than 80 percent of published oncology RWE studies traceable to a pre-registered protocol within five years and will reduce the rate of positive-only reporting measurably.","rationale":"Trial registration reduced outcome switching and publication bias; observational research has the same problems with fewer safeguards, and RWE is increasingly used in regulatory and payer decisions.","test":"Compare the proportion of pre-registered versus non-registered RWE studies reporting positive primary findings; pilot mandatory registration with two journals for one year.","maturity":"speculative","actor":"policy","cost":"small","horizonYears":2},{"id":"idea-tr1-crossover-adjusted-survival-standard","kind":"idea","name":"Pre-specified crossover-adjusted survival in every trial that allows crossover","aka":[],"tldr":"When control-arm patients switch to the new drug after their cancer grows, the survival comparison gets muddied. Trials should plan in advance how they will correct for this, and report both raw and corrected numbers.","summary":"Protocols permitting treatment switching pre-specify the adjustment method (rank-preserving structural failure time, inverse probability of censoring weighting, two-stage estimation), the assumptions, and sensitivity analyses, with the estimand defined under ICH E9(R1). Both intention-to-treat and adjusted OS are reported in the label and in HTA submissions. Health technology agencies already require this ad hoc; the idea is to make it a registration requirement.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Trial design, endpoints and cost): Davis et al., Availability of evidence of benefits on survival and quality of life of cancer drugs approved by EMA 2009-13 (BMJ 2017)","url":"https://doi.org/10.1136/bmj.j4530"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["esmo"],"pathways":[],"terms":["os","hazard-ratio"],"trials":[],"people":[],"bottlenecks":["b-trial-design"],"keyPapers":["paper-davis-bmj"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Mandatory pre-specified adjustment will reduce the frequency of OS results that are uninterpretable because of crossover, and will produce more consistent HTA decisions across countries for the same drug.","rationale":"Crossover is ethically necessary but currently destroys the OS signal in many trials, feeding disputes about value. Methods exist and are used inconsistently, often chosen after seeing the data.","test":"Audit recent oncology approvals with crossover for whether adjusted OS was pre-specified; then require it and re-audit after three years for interpretability and HTA discordance.","maturity":"early-clinical","actor":"regulator","cost":"small","horizonYears":1},{"id":"idea-tr2-animal-power-mandate","kind":"idea","name":"Pre-specified sample sizes for animal studies; no more 'representative' experiments","aka":[],"tldr":"Underpowered mouse experiments give exaggerated positive results and uninformative negatives, and papers often show one 'representative' result out of several attempts. Funders and journals should require a pre-specified power calculation, the number of independent repeats performed, and reporting of every repeat rather than the best one.","summary":"Underpowered animal studies produce exaggerated effects when positive and are uninformative when negative. Sample-size justification is required by ARRIVE and by ethics committees in principle but is rarely checked. Funders and journals could require a pre-specified power calculation, the number of independent repeats performed, and reporting of all repeats rather than a representative one.","asOf":"2026-09-08","links":[{"label":"ARRIVE guidelines","url":"https://arriveguidelines.org/"}],"tags":[],"related":["idea-tr2-arrive-audit"],"cancers":[],"sections":[],"technologies":["pdx-models"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-reproducibility","b-preclinical-models"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Enforcement increases the median group size in published in vivo efficacy studies and reduces reported effect sizes towards those seen in adequately powered replications.","rationale":"Effect-size inflation from small samples is a mathematical certainty under publication bias; the fix is procedural and cheap.","test":"Adopt at two funders; audit group sizes, repeat reporting and effect sizes in funded publications before and after.","maturity":"early-clinical","actor":"policy","cost":"small","horizonYears":1},{"id":"idea-tr2-neoadjuvant-combo-platform","kind":"idea","name":"Pre-surgery platform trials that test combinations on pathological response in months","aka":[],"tldr":"Give drug combinations before surgery and measure how much tumour remains at resection; that answer arrives in months. A standing neoadjuvant platform with a shared control arm, as I-SPY 2 runs in breast cancer, would test combinations quickly in lung, bladder, melanoma, head and neck and oesophago-gastric cancer.","summary":"I-SPY 2 established graduation of arms by pathological complete response in breast cancer. The same model applies to lung, bladder, melanoma, head and neck and oesophago-gastric cancer where neoadjuvant therapy is now standard. Each cancer needs a standing neoadjuvant platform with a shared control arm and pre-agreed rules for graduating an arm to a confirmatory trial.","asOf":"2026-09-08","links":[{"label":"I-SPY trials","url":"https://www.ispytrials.org/"}],"tags":[],"related":["major-pathological-response","neoadjuvant-io-response-adapted"],"cancers":["esophageal","head-and-neck","nsclc","melanoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["pcr","rcb","basket-umbrella-platform"],"trials":["keynote-522","nadina"],"people":[],"bottlenecks":["b-combination-space","b-trial-design"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Neoadjuvant platforms will screen at least five combination arms per year per cancer, with pathological response predicting event-free survival well enough that graduated arms confirm in phase 3 at least 60% of the time.","rationale":"Pathological complete response and major pathological response correlate with survival in breast, lung and melanoma, and the neoadjuvant window allows paired biopsies that explain why a combination did or did not work.","test":"Open a neoadjuvant platform in one cancer without one (oesophago-gastric or head and neck), graduate two arms by pathological response, and track confirmation.","maturity":"being-tested-at-scale","actor":"research","cost":"large","horizonYears":3},{"id":"idea-moon-irae-prediction-and-prevention","kind":"idea","name":"Predict immune side-effects before they happen and pre-empt them","aka":[],"tldr":"Immunotherapy can trigger dangerous attacks on the gut, lungs or heart. Use blood, gut bacteria and genetic markers to spot who is at risk and act early.","summary":"Immune-related adverse events cause treatment discontinuation and death, and their management is reactive. Autoantibody profiles, HLA types, microbiome composition, baseline cytokines and early T-cell clonal expansion are each associated with specific toxicities in retrospective series. The proposal is a prospective biomarker cohort across checkpoint inhibitor indications to derive and validate a toxicity risk model, followed by trials of pre-emptive strategies (early steroid-sparing agents, microbiome modulation, intensified monitoring) in high-risk patients.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Toxicity and quality of life are undervalued): Di Maio et al., Symptomatic toxicities experienced during anticancer treatment: agreement between patient and physician reporting (JCO 2015)","url":"https://doi.org/10.1200/JCO.2014.57.9334"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":[],"drugs":["pembrolizumab","ipilimumab"],"companies":[],"institutions":[],"pathways":[],"terms":["irae"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol","b-immunotherapy-response"],"keyPapers":["paper-di-maio-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A validated model identifies a high-risk group with at least threefold risk of grade 3+ immune toxicity, and pre-emptive management reduces severe events and discontinuations without reducing response rates.","rationale":"Toxicity and efficacy are partially separable; preventive strategies such as prophylactic vedolizumab or IL-6 blockade have early data suggesting response is preserved.","test":"Prospective 3,000-patient cohort with banked samples; then a randomised trial of pre-emptive management in model-defined high-risk patients.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":4},{"id":"idea-cost-low-dose-abiraterone-food","kind":"idea","name":"Prescribe a quarter dose of abiraterone with breakfast","aka":[],"tldr":"Taking 250 mg of abiraterone with a low-fat breakfast gives the same PSA response and testosterone suppression as the standard 1,000 mg fasting, because food increases absorption several-fold, so a quarter of the drug treats each man. The label still says fasting and no company promotes the food-effect dose, so adoption is patchy.","summary":"A randomised trial (Szmulewitz et al., JCO 2018) showed 250 mg abiraterone with a low-fat breakfast was non-inferior to 1,000 mg fasting on PSA response and testosterone suppression in metastatic castration-resistant prostate cancer, because food increases absorption several-fold. NCCN guidelines list the food-effect dose as an option. Adoption is patchy because the label still says fasting and because there is no commercial incentive to promote it. Generic abiraterone makes the absolute saving smaller in the US but large where the branded product is still used or where patients pay out of pocket.","asOf":"2026-09-10","links":[{"label":"Szmulewitz et al., JCO 2018: low-fat meal abiraterone","url":"https://doi.org/10.1200/JCO.2017.76.4381"}],"tags":[],"related":[],"cancers":["prostate"],"sections":["hormonal"],"technologies":["androgen-deprivation"],"targets":[],"drugs":["abiraterone"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["capitello-281","propel","nct05171816","nct01517802","nct03777982"],"people":[],"bottlenecks":["b-dose-optimisation","b-drug-pricing","b-global-access"],"keyPapers":["paper-szmulewitz-j-clin-oncol","paper-abiraterone-acetate-prostate-n-engl-j-med-2013","paper-abiraterone-acetate-prostate-lancet-oncol-2015","paper-abiraterone-acetate-prostate-lancet-oncol-2012"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Guideline-endorsed low-dose-with-food abiraterone will reach more than half of eligible prescriptions in health systems that adopt it as default, with no loss in time to PSA progression.","rationale":"Level 1 randomised evidence already exists; the change needs only a prescribing default and patient counselling.","test":"Health-system default switch with monitoring of PSA response, time to progression and drug spend against the prior cohort; a pragmatic trial in India or Africa where the price matters most.","maturity":"being-tested-at-scale","actor":"clinic","cost":"small","horizonYears":1},{"id":"idea-bio2-brain-met-prevention-trials","kind":"idea","name":"Prevention trials aimed only at brain metastasis","aka":[],"tldr":"Some cancers reach the brain in up to a quarter of patients. Prevention trials could aim specifically at stopping that, instead of treating it once it has happened.","summary":"Brain-penetrant agents reduce central nervous system progression in metastatic disease, and adjuvant trials have shown CNS event reductions as secondary endpoints. No trial yet uses CNS-metastasis-free survival as a primary endpoint in a population prospectively defined as CNS-high-risk by subtype and risk score. This is a designable, ownable clinical setting rather than a new mechanism.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Metastasis is understood least and studied last): Dillekås et al., Are 90% of deaths from cancer caused by metastases? (Cancer Medicine 2019)","url":"https://doi.org/10.1002/cam4.2474"}],"tags":[],"related":["lung-cancer-evidence-roadmap","idea-lung-brain-metastasis-prevention-as-a-primary-endpoint"],"cancers":["breast-her2-positive","nsclc"],"sections":[],"technologies":["mri"],"targets":[],"drugs":["tucatinib","osimertinib","alectinib","lorlatinib"],"companies":[],"institutions":[],"pathways":[],"terms":["her2-brain-metastases"],"trials":["alina","adaura","her2climb"],"people":[],"bottlenecks":["b-metastasis-biology","b-brain-delivery","b-trial-design"],"keyPapers":["paper-adaura-8-year-os-jto-2026","paper-flaura-nejm-2018","paper-dillekas-cancer-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"In prospectively identified CNS-high-risk resected disease, such as HER2-positive breast cancer with heavy nodal involvement or ALK-positive lung cancer, a brain-penetrant adjuvant regimen improves CNS-metastasis-free survival by an absolute 10% at three years.","rationale":"Adjuvant osimertinib and alectinib trials both showed large reductions in CNS events as secondary findings. Preventing brain metastasis sidesteps the delivery problem entirely by acting before the barrier becomes the obstacle.","test":"Estimate CNS event rates and effect sizes retrospectively in existing adjuvant datasets to size the trial, then run a randomised CNS-metastasis-free survival trial with protocol-mandated MRI surveillance.","maturity":"speculative","actor":"industry","cost":"large","horizonYears":8},{"id":"idea-cost-indication-based-pricing","kind":"idea","name":"Price a cancer drug by how well it works in each cancer","aka":[],"tldr":"A drug that adds a year of life in one cancer and six weeks in another sells at the same price for both; indication-specific prices would pay for the benefit actually delivered.","summary":"Most oncology drugs carry several indications, and the benefit differs from one indication to the next. Indication-based pricing sets a price per indication, either through separate national drug codes or through rebates keyed to the diagnosis on the claim. Italy and Germany use indication-level agreements; in the US, pharmacy benefit managers have run pilots. The barrier is claims data that reliably carries the indication.","asOf":"2026-09-10","links":[{"label":"ESMO Magnitude of Clinical Benefit Scale","url":"https://www.esmo.org/guidelines/esmo-mcbs"},{"label":"ASCO Value Framework update (JCO 2016)","url":"https://doi.org/10.1200/JCO.2016.68.2518"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":["pembrolizumab","nivolumab","atezolizumab"],"companies":[],"institutions":["esmo","asco"],"pathways":[],"terms":["icer-value-assessment"],"trials":[],"people":[],"bottlenecks":["b-drug-pricing","b-incentive-misalignment"],"keyPapers":["paper-schnipper-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Indication-based rebates will lower the effective price of low-benefit indications by at least 30% without reducing the launch price of high-benefit indications, and manufacturers will accept them in exchange for coverage.","rationale":"Value frameworks (ESMO-MCBS, ASCO Value Framework) already grade benefit by indication; the payment system simply ignores the grade.","test":"A Medicare Part B demonstration for three multi-indication checkpoint inhibitors with indication-linked rebates, measuring net price by indication, prescribing patterns and access.","maturity":"early-clinical","actor":"payer","cost":"medium","horizonYears":4},{"id":"idea-tr1-representativeness-in-the-label","kind":"idea","name":"Print the participation-to-prevalence ratio in every drug label and assessment report","aka":[],"tldr":"A drug's label should say plainly how well the people in its trials matched the people who get the disease: 'Black patients were 4 percent of participants and 22 percent of cases.' Doctors and patients can then judge how far to trust the result.","summary":"Labels and public assessment reports (FDA, EMA EPAR) include a standard representativeness panel: enrolled percentages by race, ethnicity, sex, age band and region beside incidence-based expected percentages, with a participation-to-prevalence ratio per stratum. The panel is machine-readable and aggregated in a public dashboard.","asOf":"2026-09-08","links":[{"label":"FDA Drug Trials Snapshots","url":"https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trials-snapshots"}],"tags":[],"related":["fda-approvals"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-diversity","b-knowledge-diffusion"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A visible ratio in the label will increase sponsor effort on representativeness and will be used by guideline committees and payers when weighing evidence for under-represented groups.","rationale":"FDA Drug Trials Snapshots already publish demographics, but separately from the label; placing the comparison in the document clinicians read makes the gap salient at prescribing.","test":"Survey clinician and guideline-committee use of the panel after introduction; track change in ratios across approvals over five years.","maturity":"speculative","actor":"regulator","cost":"small","horizonYears":1},{"id":"idea-data-privacy-preserving-linkage-tokens","kind":"idea","name":"Privacy-preserving linkage tokens for every cancer data holder","aka":[],"tldr":"Give each patient a scrambled code that is the same across hospitals, labs and registries, so records can be joined without anyone seeing names.","summary":"Record linkage across holders fails without a shared identifier; where national IDs exist (Nordics) linkage is trivial, elsewhere it is probabilistic and lossy. Privacy-preserving record linkage using salted hashes of identifiers (as used by Datavant in the US and Bloom-filter approaches in Australia and Germany) allows joining without exposing identity. The proposal mandates a common tokenisation scheme, run by a public trusted third party, for all holders of cancer data.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Data silos): AACR Project GENIE","url":"https://www.aacr.org/professionals/research/aacr-project-genie/"}],"tags":[],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-data-silos"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A common token will raise linkage rates between registries, genomic labs and hospitals from below 70 percent (probabilistic) to above 97 percent, at no measurable privacy cost.","rationale":"Where national identifiers exist, near-complete linkage has powered decades of registry research; tokens replicate the function without a national ID.","test":"Tokenise one registry, one genomic lab and one hospital system; measure linkage rate against a gold-standard manually linked subset.","maturity":"early-clinical","actor":"data","cost":"medium","horizonYears":2},{"id":"idea-fund-technique-innovation-prize","kind":"idea","name":"Prizes for unpatentable surgical and radiotherapy techniques proven in trials","aka":[],"tldr":"Nobody can patent a better way of operating or a shorter radiotherapy schedule, so nobody is rewarded for proving one. Prizes for technique improvements shown to work in trials would fill that gap.","summary":"An endowed prize programme paying substantial awards (for example $5 to $20 million shared among the trial team and institutions) for randomised trials that demonstrate a surgical or radiotherapy technique change improving survival, recurrence or major toxicity by a pre-specified margin, with the requirement that the technique is freely described and teachable. Technique innovations such as total mesorectal excision, sentinel node biopsy and hypofractionation have saved more lives and money than most drugs and earned their originators nothing comparable; a prize corrects the reward asymmetry at the margin and attracts talent to technique research.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Surgery and radiotherapy cure most, get least): Sullivan et al., Global cancer surgery (Lancet Oncology Commission 2015)","url":"https://doi.org/10.1016/S1470-2045(15)00223-5"}],"tags":[],"related":["idea-fund-cure-prize","idea-fund-surgical-trials-network","idea-fund-surgeon-scientist-pathway"],"cancers":[],"sections":[],"technologies":["sentinel-node","sbrt","robotic-surgery"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-surgery-radiation-innovation","b-incentive-misalignment"],"keyPapers":["paper-sullivan-lancet-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Announcing a standing technique prize increases the number of randomised trials of surgical and radiotherapy technique registered per year by at least a third within five years and the number of trainees entering technique-focused research.","rationale":"Prizes reward outputs without requiring exclusivity, exactly the property needed for unpatentable innovations; the Lasker and Breakthrough prizes show that recognition and money shift prestige in science. Surgery and radiotherapy lack an equivalent focused on trial-proven technique.","test":"Endow the prize, publish criteria and track technique trial registrations and applicant characteristics over five years against the prior period.","maturity":"speculative","actor":"philanthropy","cost":"medium","horizonYears":5},{"id":"idea-mtap-prmt5-mesothelioma","kind":"idea","name":"PRMT5/MAT2A synthetic lethality for MTAP-deleted mesothelioma","aka":[],"tldr":"About half of mesotheliomas have lost a gene called MTAP. That loss creates a weakness that new PRMT5 inhibitors are designed to exploit.","summary":"Roughly half of pleural mesotheliomas carry a co-deletion of CDKN2A and MTAP, and this idea proposes exploiting the weakness that MTAP loss creates. Loss of MTAP raises intracellular MTA, which partially inhibits PRMT5, so MTA-cooperative PRMT5 inhibitors such as AMG 193, MRTX1719 and BMS-986504, and MAT2A inhibitors, gain a therapeutic window that first-generation PRMT5 inhibitors lacked. The rationale is a strong genetic dependency in DepMap, an easy immunohistochemistry test for MTAP loss, and early responses in MTAP-deleted tumours including mesothelioma. At an early clinical stage, the test would be expansion cohorts then a randomised second-line trial, and it connects to the ideas on attacking the backup copy of a lost gene and grouping trials by broken mechanism.","asOf":"2026-09-07","links":[{"label":"Defining a Cancer Dependency Map: which genes each cancer cell line cannot live without (Cell 2017)","url":"https://doi.org/10.1016/j.cell.2017.06.010"}],"tags":[],"related":[],"cancers":["mesothelioma"],"sections":[],"technologies":["synthetic-lethality-approaches","crispr-screens"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["synthetic-lethality"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"MTA-cooperative PRMT5 inhibitors will produce durable responses in MTAP-deleted mesothelioma after immunotherapy, with a therapeutic window absent for first-generation PRMT5 inhibitors.","rationale":"Strong genetic dependency in DepMap; MTAP deletion is easily tested by IHC; mesothelioma has among the highest MTAP-loss frequencies of any cancer.","test":"MTAP-deleted mesothelioma expansion cohorts in ongoing phase 1/2 trials, then a randomised second-line trial versus chemotherapy.","maturity":"early-clinical"},{"id":"idea-acc-echo-tele-mentoring-oncology","kind":"idea","name":"Project ECHO tele-mentoring for district clinicians managing cancer","aka":[],"tldr":"Project ECHO is a weekly video class where district doctors and nurses present real cases to a specialist team, learn by doing, and build a network. It worked for hepatitis C and could work for cancer.","summary":"Project ECHO's hub-and-spoke tele-mentoring model, in which specialists at a hub run regular case-based video sessions with community clinicians, has shown outcomes for hepatitis C treated in primary care equal to specialist clinics. Oncology ECHO programmes exist in India, Africa, and the US but are small. Scaling structured ECHO for symptom management, palliative care, and common-cancer protocols would multiply the reach of scarce specialists.","asOf":"2026-09-08","links":[{"label":"Project ECHO","url":"https://hsc.unm.edu/echo/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-workforce","b-knowledge-diffusion","b-global-access"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Clinicians participating in six months of oncology ECHO will show measurable gains in guideline-concordant management and will refer appropriately more often, with fewer avoidable late-stage presentations from their catchments.","rationale":"The learning-by-case model produces sustained practice change where one-off courses do not, and the marginal cost per additional spoke is near zero.","test":"A stepped-wedge trial across 40 district facilities with pre-post knowledge testing, chart-audited concordance, and referral timeliness.","maturity":"being-tested-at-scale","actor":"clinic","cost":"small","horizonYears":2},{"id":"idea-fund-academic-promotion-reform","kind":"idea","name":"Promote academics for trials completed, data shared and findings replicated","aka":[],"tldr":"Universities and cancer centres would change how they promote scientists, giving credit for finishing trials, sharing data, replicating others' work and publishing failures, not just for papers in famous journals.","summary":"Cancer centres and medical schools adopt narrative CVs and explicit promotion criteria that credit trial completion and reporting, data and code deposition, registered reports, replication studies, tool and model contributions and patient-facing outputs, while discounting journal impact factor (per the San Francisco Declaration on Research Assessment). Funders reinforce this by requiring the same formats in applications. The current system rewards novel positive findings in high-impact journals, which is precisely the incentive structure that produces irreproducible preclinical cancer biology and unpublished trials.","asOf":"2026-09-08","links":[{"label":"San Francisco Declaration on Research Assessment","url":"https://sfdora.org/"}],"tags":[],"related":["nci-cancer-centers","idea-fund-trial-completion-bonus","idea-fund-open-results-bonus"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-incentive-misalignment","b-reproducibility","b-negative-results"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Centres that adopt the reformed criteria show, within five years, higher rates of trial result reporting, data deposition and replication publications by their faculty than matched centres, with no decline in external grant success.","rationale":"DORA has been signed by thousands of institutions and Utrecht University and others have removed impact factor from promotion; early evidence suggests changes in researcher behaviour where criteria are concrete. The Reproducibility Project: Cancer Biology attributes irreproducibility partly to incentives for novelty.","test":"A consortium of ten cancer centres adopts the criteria; pre-register the comparison of reporting, sharing and replication metrics with ten matched centres over five years.","maturity":"speculative","actor":"research","cost":"small","horizonYears":3},{"id":"idea-acc-lymphoedema-prospective-surveillance","kind":"idea","name":"Prospective arm-volume surveillance to catch and reverse lymphoedema early","aka":[],"tldr":"Arm swelling after breast cancer surgery is common and lifelong once established, but if caught early with simple measurements and treated with a sleeve, most cases can be prevented from becoming permanent.","summary":"Breast cancer-related lymphoedema affects a large minority of patients who have axillary surgery or radiotherapy. Prospective surveillance with bioimpedance spectroscopy or arm-volume measurement, and early compression when subclinical change is detected, reduced progression to chronic lymphoedema substantially in a randomised trial (PREVENT). Surveillance is rarely implemented. Making it a standard component of breast cancer follow-up is inexpensive.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Survivorship and late effects are neglected): NCI Office of Cancer Survivorship statistics","url":"https://cancercontrol.cancer.gov/ocs/statistics"}],"tags":[],"related":[],"cancers":["breast-hr-positive","tnbc"],"sections":["surgery","supportive-care","rejuvenation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Routine prospective surveillance with early intervention will reduce the incidence of chronic lymphoedema at three years by at least half compared with symptom-triggered management.","rationale":"Randomised evidence exists; the intervention is cheap and the condition is otherwise irreversible, so implementation is the whole problem.","test":"A stepped-wedge implementation across breast units with chronic lymphoedema incidence, quality of life, and cost as endpoints.","maturity":"being-tested-at-scale","actor":"clinic","cost":"small","horizonYears":2},{"id":"idea-prev-prostate-as-triggered-biopsy","kind":"idea","name":"Prostate active surveillance without scheduled biopsies: MRI and blood tests decide","aka":[],"tldr":"Men on active surveillance for prostate cancer have repeat biopsies every year or two, a burden that drives some towards surgery. Triggering biopsy only when MRI, PSA density or new markers change, tested against scheduled biopsy in a 2,000-man non-inferiority trial, could be just as safe with far fewer biopsies.","summary":"Men on active surveillance for prostate cancer have repeat biopsies every year or two, a burden that drives some towards surgery, so this idea triggers biopsy only when MRI, PSA density or new markers change. PRECISE MRI criteria and PSA density predict progression, MRI stability has high negative predictive value, and scheduled biopsies mostly find unchanged disease. A non-inferiority RCT would compare biomarker and MRI-triggered biopsy with protocol biopsy, using metastasis-free survival at eight years and biopsies per patient as endpoints. The test is a 2,000-man multicentre trial. At early-clinical maturity it addresses the bottlenecks Overdiagnosis and false alarms and Toxicity and quality of life are undervalued.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Overdiagnosis and false alarms): Welch & Black, Overdiagnosis in cancer (JNCI 2010)","url":"https://doi.org/10.1093/jnci/djq099"}],"tags":[],"related":["prostate-roadmap","idea-prostate-per-lesion-mri-audit-before-focal-treatment"],"cancers":["prostate"],"sections":["early-detection","imaging"],"technologies":["mri","liquid-biopsy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["pi-rads","template-mapping-biopsy"],"trials":[],"people":[],"bottlenecks":["b-overdiagnosis","b-toxicity-qol"],"keyPapers":["paper-welch-j-natl-cancer-inst"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Triggered biopsy reduces biopsies by at least 60% with metastasis-free survival non-inferior (margin 2 percentage points).","rationale":"Biopsy burden drives men to choose surgery; MRI stability has high negative predictive value.","test":"2,000-man multicentre RCT.","maturity":"early-clinical","actor":"clinic","cost":"medium","horizonYears":6},{"id":"idea-moon-hearing-protection-cisplatin","kind":"idea","name":"Protect hearing from cisplatin in adults as we now do in children","aka":[],"tldr":"Cisplatin causes permanent hearing loss. A cheap drug, sodium thiosulfate, protects children; test and roll it out for adults too.","summary":"Sodium thiosulfate is approved to reduce cisplatin ototoxicity in children with localised solid tumours after randomised trials. Adults with head and neck, testicular, lung and bladder cancers receive cisplatin in large numbers and commonly lose hearing, with no protective standard. The proposal is randomised trials of delayed sodium thiosulfate and other candidates (statins, transtympanic agents) in adult cisplatin regimens with audiometry and patient-reported hearing endpoints, with careful attention to tumour outcome non-inferiority.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Toxicity and quality of life are undervalued): Di Maio et al., Symptomatic toxicities experienced during anticancer treatment: agreement between patient and physician reporting (JCO 2015)","url":"https://doi.org/10.1200/JCO.2014.57.9334"}],"tags":[],"related":[],"cancers":["head-and-neck","urothelial","nsclc"],"sections":["rejuvenation"],"technologies":["platinum"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol"],"keyPapers":["paper-di-maio-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Otoprotection reduces clinically significant hearing loss in adults on cisplatin by at least a third without reducing tumour control.","rationale":"The mechanism (thiol scavenging of cisplatin) is not age-specific and the paediatric trials showed efficacy; adult trials have been small or absent because nobody owns the question.","test":"Phase 3 randomised trial in head and neck chemoradiation and testicular cancer with audiometric primary endpoint and progression-free survival non-inferiority.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":4},{"id":"idea-bio2-antibiotic-stewardship-io","kind":"idea","name":"Protect the gut flora of patients about to start immunotherapy","aka":[],"tldr":"Antibiotics given in the weeks before immunotherapy are linked to much worse results. A simple stewardship rule could preserve benefit at no cost.","summary":"Multiple cohort studies and meta-analyses report substantially worse survival in patients receiving broad-spectrum antibiotics within roughly 30 days before checkpoint blockade. Causality is uncertain because antibiotic use marks infection and frailty. A stewardship intervention (narrow-spectrum choice, shortest effective duration, deferral of non-urgent prophylaxis, and where necessary delaying checkpoint start) is testable and cheap either way.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (No one can predict who responds to immunotherapy): Haslam & Prasad (JAMA Network Open 2019)","url":"https://doi.org/10.1001/jamanetworkopen.2019.2535"}],"tags":[],"related":[],"cancers":["nsclc","melanoma","rcc"],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["laurence-zitvogel"],"bottlenecks":["b-immunotherapy-response","b-care-fragmentation","b-generic-repurposing"],"keyPapers":["paper-haslam-jama-netw-open"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A protocolised antibiotic stewardship bundle before checkpoint therapy improves 12-month survival compared with usual prescribing, which would establish that at least part of the observed association is causal and modifiable.","rationale":"The association is large and consistent across tumour types, and antibiotic prescribing is highly modifiable. If the effect is confounding rather than causation, the trial establishes that cheaply and stops a growing body of over-interpretation.","test":"A cluster-randomised stewardship trial across oncology units, with antibiotic exposure metrics as process outcomes and survival as the clinical endpoint, plus a microbiome substudy.","maturity":"early-clinical","actor":"clinic","cost":"small","horizonYears":3},{"id":"idea-bio1-model-authentication-mandate","kind":"idea","name":"Prove the cell line is what you say it is, or the paper does not run","aka":[],"tldr":"A troubling share of published cancer experiments use cell lines that are contaminated or mislabelled. Requiring a simple identity check before publication would stop this.","summary":"Short tandem repeat profiling costs little and detects misidentification and cross-contamination, yet compliance is patchy. Mandatory deposition of STR profiles (and, for patient-derived models, low-pass sequencing confirming donor identity and drift) at submission, checked automatically against the register of misidentified lines, would remove a known and fully solvable source of irreproducibility. Some journals already require it; enforcement is inconsistent.","asOf":"2026-09-08","links":[{"label":"ICLAC register of misidentified cell lines","url":"https://iclac.org/databases/cross-contaminations/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-preclinical-models","b-reproducibility"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Mandatory automated authentication checking at submission reduces the proportion of published oncology papers using misidentified lines to under 1 percent within three years.","rationale":"Cell-line misidentification is one of the few reproducibility problems with a cheap, definitive test and an existing reference database; the failure is purely one of enforcement.","test":"Two major journals implement automated checking for one year; measure rejection or correction rate and compare with matched journals that do not.","maturity":"preclinical-evidence","actor":"policy","cost":"small","horizonYears":2},{"id":"idea-tr2-cell-line-authentication-mandate","kind":"idea","name":"Prove your cell lines are what you say they are, or the paper is not published","aka":[],"tldr":"A large share of cancer research has been done on cells that were mislabelled or contaminated. A cheap DNA fingerprint test can prove identity; journals and funders should require it.","summary":"Cross-contaminated and misidentified cell lines (the ICLAC register lists over 500) continue to be used in thousands of papers. Short tandem repeat profiling costs under a hundred dollars per line. Some journals and NIH recommend authentication; few enforce it. A mandate that every paper and grant using cell lines deposits a recent STR profile matched to Cellosaurus, with funders covering the cost, would close a known, fixable source of irreproducibility.","asOf":"2026-09-08","links":[{"label":"ICLAC register of misidentified cell lines","url":"https://iclac.org/databases/cross-contaminations/"},{"label":"Cellosaurus","url":"https://www.cellosaurus.org/"}],"tags":[],"related":["cancer-models","idea-tr2-cell-line-passport"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-reproducibility","b-preclinical-models"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Enforcement at ten major journals and two funders reduces the share of new oncology papers using known misidentified lines from the several percent found in audits to under 0.5% within three years.","rationale":"The problem is fully characterised, the test is cheap and standardised (ANSI/ATCC ASN-0002), and enforcement is the only missing element.","test":"Adopt the mandate at participating journals; audit a random sample of published papers annually for compliance and for use of misidentified lines.","maturity":"early-clinical","actor":"policy","cost":"small","horizonYears":1},{"id":"idea-reg-provisional-price-until-os","kind":"idea","name":"Provisional prices for surrogate-endpoint approvals, reset when survival data arrive","aka":[],"tldr":"Drugs approved on early signs of benefit are paid for as if they had proved they extend life. Pay a provisional price and adjust it, up or down, when the survival data come in.","summary":"Most accelerated oncology approvals rest on response rate or progression-free survival, and a substantial share later fail to show survival benefit, yet prices are set at launch and rarely fall. Coverage-with-evidence-development schemes exist (the UK Cancer Drugs Fund, Germany's post-launch benefit reassessment) but price adjustment is negotiated rather than automatic. The proposal is a contractual price schedule fixed at launch: a provisional price, a higher price if the confirmatory trial shows survival benefit above a threshold, a sharply lower price or rebate if it does not, with the payer co-funding registry follow-up.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Prices and value): Prasad, De Jesús & Mailankody, The high price of anticancer drugs: origins, implications, barriers, solutions (Nat Rev Clin Oncol 2017)","url":"https://doi.org/10.1038/nrclinonc.2017.31"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["accelerated-approval","pfs","os"],"trials":[],"people":[],"bottlenecks":["b-drug-pricing","b-regulatory-fragmentation"],"keyPapers":["paper-prasad-nat-rev-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Automatic reset contracts reduce payer spend on drugs that fail confirmatory trials by at least half and do not reduce the speed of uptake of drugs that later confirm benefit.","rationale":"Aligning price to eventual evidence rewards drugs that work and shares the uncertainty that accelerated approval creates, instead of placing it entirely on payers and patients.","test":"Model the scheme retrospectively on the last decade of accelerated oncology approvals in one market; then apply prospectively to all new conditional approvals for five years.","maturity":"early-clinical","actor":"payer","cost":"small","horizonYears":5},{"id":"idea-psma-pet-guided-mdt","kind":"idea","name":"PSMA-PET-guided metastasis-directed therapy as a curative strategy in oligorecurrent prostate cancer","aka":[],"tldr":"When PSMA PET finds only a few spots after surgery, zap each spot with focused radiation and delay or avoid lifelong hormone therapy.","summary":"The idea is to use PSMA PET after prostate surgery to find the few sites of recurrence and treat each with stereotactic radiotherapy plus short-course androgen deprivation. The oligometastatic state is real in prostate cancer, the radiotherapy is ablative and cheap, and PSMA PET removes the staging blind spot that undermined older trials such as ORIOLE and STOMP. The hypothesis is better metastasis-free and ADT-free survival than systemic therapy alone, though whether it changes survival or merely postpones hormone therapy is unproven. The test is a randomised phase 3 with PSMA PET at baseline and progression and ctDNA as a stratifier; PEACE V/STORM and NRG GU011 are under way, so it is being tested at scale.","asOf":"2026-09-06","links":[{"label":"ORIOLE: observation versus stereotactic ablative radiation for oligometastatic prostate cancer (JAMA Oncology 2020)","url":"https://doi.org/10.1001/jamaoncol.2020.0147"}],"tags":[],"related":["prostate-roadmap","idea-prostate-randomise-the-sequence-not-only-the-drugs"],"cancers":["prostate"],"sections":[],"technologies":["psma-pet","sbrt"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["oligometastatic","biochemical-recurrence"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-phillips-jama-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"PSMA-PET-directed SBRT to ≤5 metastases, with short-course ADT, improves metastasis-free and ADT-free survival versus systemic therapy alone in oligorecurrent disease.","rationale":"Oligometastatic state is real in prostate cancer; SBRT is ablative and cheap; PSMA PET removes the staging blind spot that undermined older trials.","test":"Randomised phase 3 with PSMA PET at baseline and progression, ADT-free survival and MFS endpoints, ctDNA and PSMA-PET total-volume as stratifiers.","maturity":"being-tested-at-scale"},{"id":"idea-reg-public-cell-therapy-foundries","kind":"idea","name":"Public cell-therapy foundries at cancer centres for academics and start-ups","aka":[],"tldr":"Building a cell-therapy factory costs tens of millions, so most good academic ideas never reach patients. Shared public facilities would give them a route to the clinic.","summary":"The UK Cell and Gene Therapy Catapult, Canada's CCRM and several US academic GMP facilities show that shared, publicly funded manufacturing can carry academic products through early trials. The proposal is a national network of foundries co-located with cancer centres, each with standardised closed automated platforms, a shared quality system, and transparent booking and pricing, funded to provide first-in-human manufacturing at marginal cost for academic and start-up programmes, with a fast route for successful products into the hospital-made network or industry.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Manufacturing cost and time for living and radioactive medicines): Hernandez, Prasad & Gellad, Total costs of chimeric antigen receptor T-cell immunotherapy (JAMA Oncology 2018)","url":"https://doi.org/10.1001/jamaoncol.2018.0977"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["car-t","til-therapy","tcr-t"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-manufacturing-cell-therapy","b-translational-valley"],"keyPapers":["paper-hernandez-jama-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Foundry networks double the number of academic cell-therapy INDs per year in participating countries within five years and cut the cost of a first-in-human manufacturing campaign by at least half.","rationale":"Manufacturing access, not scientific quality, is the stated limiting factor for most academic cell-therapy programmes; shared infrastructure has the same economics as sequencing cores and cryo-EM facilities.","test":"Fund three foundries, track INDs supported, cost per campaign and time from award to first patient, and compare with academic programmes in regions without foundry access.","maturity":"early-clinical","actor":"policy","cost":"large","horizonYears":4},{"id":"idea-fund-sovereign-first-in-class-coinvestment","kind":"idea","name":"Public co-investment in first-in-class phase 1 with a royalty return","aka":[],"tldr":"A public investment fund would match private money in the riskiest early trials of truly new cancer drugs, taking a small share of future royalties so that taxpayers gain when the bets pay off.","summary":"A sovereign or supranational fund co-invests one-to-one alongside private investors in phase 1 trials of assets that meet a first-in-class test (a target or mechanism with no approved analogue), in exchange for a royalty stake or equity. The fund's return is portfolio-level and long-term; its purpose is to lower the private cost of capital for novel mechanisms relative to me-too assets. The Cancer Prevention and Research Institute of Texas (CPRIT) and the California Institute for Regenerative Medicine (CIRM) show public bodies can invest in translational biotech with revenue-sharing and attract companies; the EU's Innovative Health Initiative and BARDA venture arms are related models.","asOf":"2026-09-08","links":[{"label":"CPRIT","url":"https://www.cprit.texas.gov/"},{"label":"CIRM","url":"https://www.cirm.ca.gov/"}],"tags":[],"related":["idea-fund-ind-enabling-fund","idea-fund-royalty-pool-academic-assets","idea-fund-phase-two-failure-reinsurance"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["cprit"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-incentive-misalignment","b-translational-valley"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Public co-investment reduces the first-in-class discount in private financing (the gap in valuation and time to raise between novel and follow-on assets) measurably within five years and yields a portfolio return that covers the fund's costs within fifteen.","rationale":"CPRIT has committed billions with a documented multiplier in private follow-on investment and company relocation; CIRM funded therapies now in late-stage trials. Public capital is patient and can accept the higher failure rate of novelty in exchange for a share of rare large wins.","test":"Capitalise a fund at $500 million, invest only in assets passing an independent first-in-class test, and compare private follow-on financing and time-to-phase-2 of funded assets against matched unfunded novel assets after five years.","maturity":"speculative","actor":"policy","cost":"large","horizonYears":6},{"id":"idea-acc-gbci-country-dashboards","kind":"idea","name":"Public country dashboards for the three WHO breast cancer targets","aka":[],"tldr":"The WHO set three simple goals for breast cancer: most cancers found early, diagnosis within 60 days, and most patients finishing treatment. Every country should publish how it is doing on each, every year.","summary":"The WHO Global Breast Cancer Initiative pillars are: at least 60% of invasive cancers diagnosed at stage I-II, diagnosis within 60 days of presentation, and at least 80% of patients completing multimodal treatment. These are measurable with modest registry and hospital data. A public, comparable dashboard would focus ministries and donors on the delivery gaps rather than on new technology, and would show which policy changes move the numbers.","asOf":"2026-09-08","links":[{"label":"WHO Global Breast Cancer Initiative","url":"https://www.who.int/initiatives/global-breast-cancer-initiative"}],"tags":[],"related":["globocan"],"cancers":["breast-hr-positive","tnbc","breast-her2-positive"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-global-access","b-care-fragmentation","b-real-world-evidence"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Countries publishing annual GBCI indicators will improve at least two of the three indicators by ten percentage points within four years, faster than non-reporting comparators.","rationale":"Measurement with public accountability drove vaccine coverage and maternal mortality reporting; breast cancer has clear, accepted indicators but no reporting habit.","test":"Support ten countries to report baseline and annual indicators; compare trajectories with matched non-reporting countries using registry data.","maturity":"being-tested-at-scale","actor":"policy","cost":"medium","horizonYears":4},{"id":"idea-data-quality-scorecards","kind":"idea","name":"Public data-quality scorecards for every cancer centre","aka":[],"tldr":"Publish a simple report card showing how complete, timely and standard each hospital's cancer data are, so poor recording becomes visible and fixable.","summary":"Data quality is invisible and therefore unmanaged. A public scorecard per centre (completeness of stage and biomarkers, timeliness of submission, mCODE conformance, outcome capture) published quarterly by the registry or payer would create reputational pressure and allow improvement to be tracked, in the same way that hospital quality dashboards changed surgical mortality reporting.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Data silos): AACR Project GENIE","url":"https://www.aacr.org/professionals/research/aacr-project-genie/"}],"tags":[],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-data-silos","b-real-world-evidence"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Public scorecards will raise stage completeness and timeliness in the bottom quartile of centres by at least 20 percentage points within two years.","rationale":"Public reporting of surgical outcomes (New York cardiac surgery, UK cardiac surgery) improved performance through attention and peer comparison; data quality is more directly controllable by the centre than clinical outcomes.","test":"Publish scorecards for centres in one region; compare completeness trends with a region receiving the same metrics privately.","maturity":"speculative","actor":"data","cost":"small","horizonYears":2},{"id":"idea-tr2-open-cdx-validation-sets","kind":"idea","name":"Public gold-standard datasets for validating every cancer biomarker test","aka":[],"tldr":"Anyone building a new test for HER2, PD-L1 or tumour DNA should be able to check it against the same public reference set. Today each developer validates on private data nobody can inspect.","summary":"Analytical validation of biomarker tests uses proprietary sample sets, making performance claims incomparable. A public repository of consensus-annotated cases per biomarker (whole slide images with multi-pathologist scores, sequencing data with orthogonally confirmed variants, plasma samples with defined variant allele fractions) would allow head-to-head benchmarking and independent verification of any test or algorithm, including AI-based ones.","asOf":"2026-09-08","links":[{"label":"Genome in a Bottle","url":"https://www.nist.gov/programs-projects/genome-bottle"}],"tags":[],"related":["idea-tr2-liquid-biopsy-challenge","idea-tr2-pdl1-digital-calibration"],"cancers":[],"sections":[],"technologies":["digital-pathology-ai","liquid-biopsy","ngs"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-biomarker-validation","b-ai-validation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Tests benchmarked on the public sets will show performance differences hidden by developer-reported validations, and regulators will begin requiring performance on the reference sets within three years.","rationale":"ImageNet-style benchmarks drove progress and honesty in machine learning; the Genome in a Bottle reference genomes did the same for variant calling.","test":"Release reference sets for HER2, PD-L1 and ctDNA; invite all commercial and academic tests to report; publish a leaderboard.","maturity":"early-clinical","actor":"data","cost":"medium","horizonYears":2},{"id":"idea-reg-academic-cart-at-cost-coverage","kind":"idea","name":"Public payers cover academic CAR-T at cost as a benchmark for commercial prices","aka":[],"tldr":"Hospitals in Spain make their own CAR-T for a third of the commercial price. Paying for such products at cost gives health systems a lever in negotiating with companies.","summary":"ARI-0001 and similar academic products are reimbursed in Spain under the hospital exemption at a fraction of commercial list prices, and published outcomes are comparable in matched populations. The proposal is for other public payers to establish explicit coverage of academic point-of-care CAR-T at audited cost plus a fixed margin, publish that cost, and use it as the reference price in negotiations for commercial products in the same indication, creating a competitive benchmark that does not otherwise exist for single-source therapies.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Prices and value): Prasad, De Jesús & Mailankody, The high price of anticancer drugs: origins, implications, barriers, solutions (Nat Rev Clin Oncol 2017)","url":"https://doi.org/10.1038/nrclinonc.2017.31"}],"tags":[],"related":["idea-reg-point-of-care-cart-network"],"cancers":[],"sections":[],"technologies":["car-t"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-drug-pricing","b-manufacturing-cell-therapy"],"keyPapers":["paper-prasad-nat-rev-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Payers that cover academic CAR-T at cost negotiate commercial CAR-T prices at least 25% lower than payers without an academic alternative within three years, and treat more patients per unit spend.","rationale":"Monopoly pricing persists where there is no alternative; a credible, reimbursed public-sector alternative is the fastest way to create one for cell therapies, since biosimilar-style competition does not yet exist.","test":"Compare commercial CAR-T net prices and patient volumes between Spain and comparable European countries; replicate by establishing academic coverage in one further country and remeasuring after three years.","maturity":"early-clinical","actor":"payer","cost":"medium","horizonYears":3},{"id":"idea-tr2-termination-reports","kind":"idea","name":"Public post-mortem reports when a cancer drug programme is stopped","aka":[],"tldr":"When an aeroplane crashes, an independent report explains why so it does not happen again. When a cancer drug programme is abandoned, nothing is written. Change that.","summary":"Programme discontinuations are announced in earnings calls with a sentence. A structured termination report (target and mechanism, models used, what was predicted versus observed in humans, pharmacokinetics achieved, toxicities, the decision rationale, and lessons) published within twelve months of discontinuation, under a standard template, would turn each failure into shared learning. Precedents: aviation safety reporting, and the few published examples such as the analysis of the anti-CD47 and Rova-T programmes.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Failures are hidden): Anderson et al., Compliance with results reporting at ClinicalTrials.gov (NEJM 2015)","url":"https://doi.org/10.1056/NEJMsa1409364"}],"tags":[],"related":["idea-tr2-failure-taxonomy"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":["rovalpituzumab-tesirine","magrolimab","epacadostat"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-negative-results","b-knowledge-diffusion"],"keyPapers":["paper-anderson-n-engl-j-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Regular publication of termination reports will reduce the number of subsequent programmes against the same target with the same failure mode by at least a third, measurable in pipeline databases over five years.","rationale":"Each failure carries information about targets, models and endpoints that the next entrant lacks. Duplicated failures against IDO1, CD47 and DLL3 ADCs show the cost of silence.","test":"Persuade three sponsors to publish reports for their next five discontinued oncology programmes; survey competitors and academics on whether the reports changed decisions.","maturity":"speculative","actor":"industry","cost":"small","horizonYears":2},{"id":"idea-data-procurement-open-api-clauses","kind":"idea","name":"Public procurement clauses banning data export fees and lock-in","aka":[],"tldr":"Hospitals buying cancer software with public money would be required to include contract terms guaranteeing free, standard data export and no penalties for switching.","summary":"Vendors often charge for data extraction or restrict interfaces. Model procurement clauses (open APIs, no export fees, data portability on contract end, right to audit) adopted by national purchasers would change vendor behaviour faster than regulation. The US 21st Century Cures Act information-blocking rules are the closest precedent; procurement is a complementary lever available to any public health system.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Data silos): AACR Project GENIE","url":"https://www.aacr.org/professionals/research/aacr-project-genie/"}],"tags":[],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-data-silos"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Adoption of standard clauses by national purchasers will eliminate export fees in new contracts within two years and reduce reported integration time for research extracts by a third.","rationale":"Procurement power moved the software industry to open standards in government IT; hospital systems are one of the largest public software purchases and have not used the lever.","test":"Publish model clauses; get three national purchasers to adopt them; survey cancer centres on export costs and integration times before and after.","maturity":"speculative","actor":"policy","cost":"small","horizonYears":2},{"id":"idea-reg-cart-potency-reference-standards","kind":"idea","name":"Public reference standards and potency assays for CAR-T so every lab measures alike","aka":[],"tldr":"There is no agreed ruler for measuring how strong a CAR-T product is. Shared reference materials would let hospitals, companies and regulators compare products fairly.","summary":"How strongly a CAR-T batch kills its target cells is the release attribute regulators worry about most for cell therapies, and every developer measures it with a different in-house assay, making comparability, decentralised manufacturing and biosimilar-like competition impossible. The proposal is a programme, led by a metrology institute such as NIST or NIBSC with the ISCT and regulators, to produce certified reference CAR-T cell materials, reference target cells and standardised cytotoxicity and cytokine assays with published acceptance criteria, made available at cost.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Manufacturing cost and time for living and radioactive medicines): Hernandez, Prasad & Gellad, Total costs of chimeric antigen receptor T-cell immunotherapy (JAMA Oncology 2018)","url":"https://doi.org/10.1001/jamaoncol.2018.0977"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["car-t"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-manufacturing-cell-therapy","b-reproducibility"],"keyPapers":["paper-hernandez-jama-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Adoption of reference standards reduces inter-laboratory coefficient of variation in CAR-T potency measurement from above 40% to below 15% and is accepted by FDA and EMA as the basis for site-to-site comparability without clinical bridging.","rationale":"Reference standards underpinned the biosimilar revolution and the standardisation of flow cytometry for CD34 counting. Cell-therapy potency is technically harder but not different in kind.","test":"Produce pilot reference materials, run an international ring trial across 20 laboratories, and publish variance before and after standardised protocols.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":3},{"id":"idea-fund-surgical-outcomes-public-reporting","kind":"idea","name":"Public risk-adjusted outcome reporting for cancer surgery to drive centralisation","aka":[],"tldr":"Where you have your cancer operation strongly affects whether you survive it. Publishing each hospital's adjusted results would push complex surgery towards the centres that do it well.","summary":"National mandatory reporting of risk-adjusted 90-day mortality, major complications, margin status, lymph node yield and volume for the most complex cancer operations (oesophagectomy, pancreatectomy, gastrectomy, cystectomy, hepatectomy, lung resection), published by hospital and, for high-volume procedures, by surgeon, with minimum volume thresholds for commissioning. The volume-outcome relationship in complex cancer surgery is among the most robust findings in health services research; the Netherlands, Denmark and parts of England have centralised and improved mortality. Public reporting plus commissioning thresholds is a policy lever that requires no new science and little money.","asOf":"2026-09-08","links":[{"label":"ACS NSQIP","url":"https://www.facs.org/quality-programs/data-and-registries/acs-nsqip/"}],"tags":[],"related":["idea-fund-surgical-video-registry","idea-fund-device-technique-registry"],"cancers":["esophageal","pancreatic","gastric","urothelial"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["nki"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-surgery-radiation-innovation","b-care-fragmentation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Mandatory public reporting with volume thresholds reduces 90-day mortality for oesophagectomy and pancreatectomy by at least a quarter within three years through centralisation and quality improvement, without reducing access measured by resection rates.","rationale":"Dutch centralisation of oesophageal and pancreatic surgery reduced mortality substantially; the Netherlands' DICA audit and Sweden's registries show public, audited outcomes drive improvement. Many systems still permit very low-volume complex cancer surgery.","test":"Introduce reporting and thresholds in one country and compare mortality, complication and resection rates with the preceding period and with a country without reporting.","maturity":"being-tested-at-scale","actor":"policy","cost":"small","horizonYears":3},{"id":"idea-fund-public-option-generic-oncology","kind":"idea","name":"Public-option manufacturing for essential generic cancer drugs in shortage","aka":[],"tldr":"Cheap, essential chemotherapy drugs such as cisplatin keep running short because there is little profit in making them. A publicly-backed non-profit manufacturer would guarantee supply at a fair price.","summary":"Extend the Civica Rx and California CalRx model to a portfolio of essential oncology generics that repeatedly fall into shortage (cisplatin, carboplatin, methotrexate, fluorouracil, vincristine, etoposide, BCG): a non-profit manufacturer or contracted network with public capital, long-term purchase agreements from hospital systems and national payers, redundant production sites, and transparent cost-plus pricing. Where the public option also supplies low- and middle-income countries through pooled procurement, it addresses global access at the same time. The problem is not scientific; it is a market that rewards exit from low-margin sterile injectables.","asOf":"2026-09-08","links":[{"label":"Civica Rx","url":"https://civicarx.org/"},{"label":"CalRx","url":"https://calrx.ca.gov/"}],"tags":[],"related":["idea-fund-global-cancer-fund","idea-fund-public-car-t-manufacturing"],"cancers":[],"sections":[],"technologies":["platinum","cytotoxic-chemotherapy"],"targets":[],"drugs":["carboplatin","paclitaxel"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-incentive-misalignment","b-global-access","b-drug-pricing"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A public-option supplier covering the ten most shortage-prone oncology generics eliminates treatment delays attributable to those shortages in participating health systems within three years and holds prices within 20% of the pre-shortage median.","rationale":"Civica has supplied dozens of shortage-prone hospital generics since 2018 with stable prices; the 2023 cisplatin and carboplatin shortage in the US forced rationing of curative treatment, an outcome that would be unthinkable for a high-margin product. Public options for essential goods are a standard response to thin-market failure.","test":"Fund one non-profit line for cisplatin and carboplatin with purchase commitments from a consortium of cancer centres, and track fill rates, delays and prices against the national market over two years.","maturity":"early-clinical","actor":"policy","cost":"large","horizonYears":3},{"id":"idea-reg-lmic-public-cart-manufacturing","kind":"idea","name":"Public-sector CAR-T manufacturing in India, Brazil and South Africa under $50,000","aka":[],"tldr":"India has shown CAR-T can be made for a tenth of the US price. Public production in large middle-income countries could make it available to millions who are currently excluded.","summary":"NexCAR19 (ImmunoACT, Tata Memorial and IIT Bombay) was approved in India in 2023 at around $40,000; Brazil's Fiocruz and Butantan and China's academic centres are building comparable capacity. The proposal is a coordinated public-sector programme in three to five large middle-income countries with shared vector supply, shared training, a common product dossier adapted for national regulators, and outcome registries, aimed at treating relapsed B-cell malignancies at under $50,000 per dose within public health systems.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Manufacturing cost and time for living and radioactive medicines): Hernandez, Prasad & Gellad, Total costs of chimeric antigen receptor T-cell immunotherapy (JAMA Oncology 2018)","url":"https://doi.org/10.1001/jamaoncol.2018.0977"}],"tags":[],"related":[],"cancers":["all-leukemia","dlbcl"],"sections":[],"technologies":["car-t"],"targets":[],"drugs":[],"companies":[],"institutions":["tata-memorial"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-manufacturing-cell-therapy","b-global-access"],"keyPapers":["paper-hernandez-jama-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Public manufacturing programmes treat at least 5,000 patients a year across participating countries within five years at under $50,000 per dose, with complete response rates in relapsed B-ALL and lymphoma comparable to published academic series.","rationale":"Labour, facility and vector costs are far lower in these settings and the demand is enormous; the Indian precedent shows regulatory approval and manufacturing are achievable, and cross-country sharing of vector and know-how spreads fixed costs.","test":"Fund two additional national programmes to reach approval using shared vector and process, and report cost, throughput and outcomes at three years against the Indian precedent.","maturity":"early-clinical","actor":"policy","cost":"large","horizonYears":5},{"id":"idea-data-open-weights-for-public-funded-ai","kind":"idea","name":"Publicly funded cancer AI must release open weights and model cards","aka":[],"tldr":"If public or charity money paid to build a cancer AI model, the model itself (not just a paper about it) must be released so others can test, improve and use it.","summary":"Most publicly funded cancer AI is described in papers but the trained model is never released, so it cannot be independently validated or built on. The proposal makes release of weights, code, a model card and evaluation data (or an evaluation API where data cannot be shared) a condition of grant funding, mirroring open-access and data-sharing policies, with a governed-access route for models with genuine dual-use or privacy concerns.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (AI that is built but not validated or deployed): Wu et al., How medical AI devices are evaluated: limitations and recommendations from an analysis of FDA approvals (Nature Medicine 2021)","url":"https://doi.org/10.1038/s41591-021-01312-x"}],"tags":[],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["nci","cruk"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-ai-validation","b-reproducibility"],"keyPapers":["paper-wu-nat-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Open weights will lead to independent external validations for a majority of funded models within two years of release (versus almost none now) and to reuse in downstream tools, increasing the return on public AI funding.","rationale":"Open-source releases in general machine learning are reproduced, audited and extended within weeks; closed medical models are neither validated nor used beyond the originating lab.","test":"One funder adopts the policy for a funding cycle; count external validations and downstream uses of funded models at 24 months versus a prior cycle.","maturity":"speculative","actor":"philanthropy","cost":"small","horizonYears":2},{"id":"idea-tr1-public-dose-reduction-trials-of-approved-drugs","kind":"idea","name":"Publicly funded dose-reduction trials of expensive approved drugs","aka":[],"tldr":"Some expensive approved cancer drugs probably work as well at lower doses, as reduced-dose abiraterone with food and extended-interval checkpoint inhibitors suggest. Companies will not test this, so payers should fund randomised non-inferiority trials prioritised by spend and pharmacology, and use the results in reimbursement.","summary":"Payers and public agencies fund randomised non-inferiority trials of reduced doses or less frequent schedules of high-cost approved agents, prioritised by spend and by pharmacological plausibility (saturated target, flat exposure-response, long half-life). Precedents include reduced-dose abiraterone with food and reduced-dose or extended-interval checkpoint inhibitors. Results are used directly in reimbursement.","asOf":"2026-09-08","links":[{"label":"The Anticancer Fund","url":"https://www.anticancerfund.org/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["checkpoint-inhibitor","kinase-inhibitors"],"targets":[],"drugs":["pembrolizumab","nivolumab","imatinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-dose-optimisation","b-drug-pricing","b-incentive-misalignment"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"At least half of well-chosen dose-reduction trials will demonstrate non-inferiority, and the savings from adopted reductions will exceed the trial costs within two years of read-out.","rationale":"The pharmacology of several blockbuster agents suggests over-dosing; the financial return for payers is immediate and large, and the incentive gap for sponsors is structural.","test":"A payer consortium funds five such trials over five years and reports non-inferiority results and realised savings.","maturity":"being-tested-at-scale","actor":"payer","cost":"medium","horizonYears":4},{"id":"idea-reg-public-deescalation-trials-for-cost","kind":"idea","name":"Publicly funded trials of lower and less frequent doses of expensive cancer drugs","aka":[],"tldr":"Abiraterone at a quarter dose with food matches full-dose exposure, and pembrolizumab and nivolumab can be given at longer intervals, but no manufacturer will fund trials that cut its own revenue. A public 'value trials' fund would run non-inferiority trials of lower doses and longer intervals for the highest-spend cancer drugs, with payers committing to adopt positive results.","summary":"Abiraterone at a quarter dose with food matched full-dose exposure; extended-interval pembrolizumab and nivolumab are supported by pharmacology; several kinase inhibitors are effective at reduced doses with less toxicity. Because no manufacturer will fund trials that cut its own revenue, these questions are answered slowly by academic groups. The proposal is a dedicated public 'value trials' fund (modelled on the Netherlands' ZonMw and the UK NIHR programmes) that prioritises dose and schedule de-escalation of the highest-spend oncology drugs using non-inferiority designs, with payers committing to adopt positive results.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Prices and value): Prasad, De Jesús & Mailankody, The high price of anticancer drugs: origins, implications, barriers, solutions (Nat Rev Clin Oncol 2017)","url":"https://doi.org/10.1038/nrclinonc.2017.31"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":["pembrolizumab","nivolumab","osimertinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-drug-pricing","b-dose-optimisation"],"keyPapers":["paper-prasad-nat-rev-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Each $10 million invested in de-escalation trials returns at least $100 million a year in payer savings within five years of readout, with non-inferior survival and lower toxicity in the de-escalated arms.","rationale":"The return on de-escalation trials is enormous because the drugs are already widely used; the barrier is purely who pays for the trial. The Netherlands' programme has already reported savings many times its cost.","test":"Fund five non-inferiority trials targeting the five highest-spend oncology drugs in one health system, and audit realised savings and clinical outcomes at five years.","maturity":"being-tested-at-scale","actor":"policy","cost":"medium","horizonYears":4},{"id":"idea-prostate-per-lesion-mri-audit-before-focal-treatment","kind":"idea","name":"Publish a per-lesion miss rate for every prostate MRI service before it is allowed to guide focal treatment","aka":["per-lesion MRI audit prostate","whole-mount pathology audit focal therapy","MRI miss rate reporting"],"tldr":"Prostate MRI is good at telling you whether a man has a serious cancer and poor at telling you where all of it is. It missed at least one significant tumour in a third of men in the study that checked it against the whole removed prostate. Services that treat part of the gland, or follow men on imaging alone, are relying on the number they do not measure.","summary":"PROMIS established per-patient performance: sensitivity of 93 percent for clinically significant cancer against a template mapping biopsy reference, with specificity of 41 percent, which is what justifies using the scan to decide whether to biopsy. Johnson and colleagues measured per-lesion performance by co-registering scans with whole-mount pathology in 588 prostatectomy specimens: 45 percent of all 1,213 foci detected, 65 percent of clinically significant ones, at least one clinically significant focus missed in 34 percent of men overall and 45 percent of men with multifocal disease.\n\nThose two numbers answer different questions and are routinely quoted as if they answered the same one. A triage decision needs the first. Treating one part of the gland and leaving the rest, or following a man for years on imaging without biopsy, needs the second, and no service publishes it. Every centre performing radical prostatectomy after magnetic resonance imaging already generates the data required, because it has the scan and the whole gland. The proposal is that per-lesion sensitivity against whole-mount pathology, stratified by lesion size and grade, becomes a published quality metric, and a precondition for offering focal ablation or imaging-only surveillance.","asOf":"2026-09-25","links":[],"tags":["prostate-evidence"],"related":["idea-fund-device-technique-registry","idea-fund-ablation-versus-surgery-trials","idea-prev-prostate-as-triggered-biopsy","prostate-roadmap"],"cancers":["prostate","prostate-low-risk","prostate-intermediate-risk","prostate-high-risk"],"sections":["imaging","diagnostics","surgery"],"technologies":["mri","active-surveillance","prostate-screening-psa-mri"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["gleason-grade-group","prostatectomy","whole-mount-pathology","pi-rads","template-mapping-biopsy"],"trials":[],"people":[],"bottlenecks":["b-biomarker-validation","b-surgery-radiation-innovation","b-overdiagnosis","b-real-world-evidence","b-ai-validation"],"keyPapers":["paper-johnson-mpmri-individual-foci-eur-urol-2019","paper-ahmed-promis-multiparametric-mri-lancet-2017","paper-precision-mri-targeted-biopsy-nejm-2018","paper-klotz-active-surveillance-jco-2015"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Per-lesion sensitivity of multiparametric magnetic resonance imaging against whole-mount pathology varies substantially between centres and readers, this variation is measurable from data centres already hold, and publishing it changes which centres offer focal therapy and imaging-only surveillance and reduces the rate of clinically significant cancer found outside the treated or monitored region.","rationale":"The per-patient and per-lesion figures differ by around 30 percentage points in the best available study, and the gap is exactly where focal therapy and imaging-only follow-up operate. Reader and protocol variation in prostate magnetic resonance imaging is well documented and is the standing argument for certification, but certification is currently based on reading test cases rather than on a centre's own outcomes. The audit proposed here requires no new imaging, no new pathology and no new consent beyond routine data use: the scan, the whole-mount specimen and the co-registration software all exist, and the comparison is already done retrospectively in research settings. Making it routine turns an unmeasured risk into a published number that patients and commissioners can act on.","test":"A multicentre audit in which every centre performing radical prostatectomy after multiparametric magnetic resonance imaging co-registers the pre-operative scan with the whole-mount specimen and reports per-lesion sensitivity for all foci and for clinically significant foci, stratified by lesion diameter, grade group, index versus non-index status and prostate-specific antigen density, with reader-level and scanner-level breakdown. Publish centre-level figures annually. Then test the consequence: a registry comparison of focal therapy outcomes (clinically significant cancer in the untreated gland at three years) between centres above and below the median per-lesion sensitivity. Two years to the first audit round.","maturity":"early-clinical","actor":"clinic","cost":"small","horizonYears":3},{"id":"idea-tr2-eqa-public-results","kind":"idea","name":"Publish each laboratory's biomarker proficiency results","aka":[],"tldr":"Labs already get tested on whether they score biomarkers correctly, but the results are private. Publishing them would let hospitals and patients avoid labs that get it wrong.","summary":"External quality assessment schemes (NordiQC, UK NEQAS, CAP) show that a meaningful fraction of laboratories fail proficiency runs for HER2, PD-L1, ALK and other predictive markers. Results are confidential. Mandatory participation for any laboratory running companion diagnostics and public reporting of pass rates by laboratory, as is done for hospital infection rates, would create accountability and steer referrals.","asOf":"2026-09-08","links":[{"label":"UK NEQAS","url":"https://ukneqas.org.uk/"},{"label":"NordiQC","url":"https://www.nordiqc.org/"}],"tags":[],"related":["idea-tr2-her2-low-reference-materials"],"cancers":[],"sections":[],"technologies":["histopathology-ihc","companion-diagnostic"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-biomarker-validation","b-care-fragmentation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Public reporting will raise the proportion of laboratories passing predictive-marker EQA runs above 95% within three years, and reduce the between-laboratory variation in positivity rates.","rationale":"Public performance reporting improved outcomes in cardiac surgery and hospital-acquired infections. Laboratory medicine has the data and has resisted transparency.","test":"Publish results for one marker in one country; measure pass rates and referral shifts over two years.","maturity":"early-clinical","actor":"regulator","cost":"small","horizonYears":2},{"id":"idea-reg-publish-all-rejections","kind":"idea","name":"Publish every complete response letter and negative opinion across all regulators","aka":[],"tldr":"When a regulator rejects a cancer drug, the reasons are usually secret. Publishing them everywhere would stop other countries and companies repeating the same mistakes.","summary":"FDA began publishing complete response letters in 2025; EMA publishes refusal assessment reports; most other regulators publish nothing on negative decisions. Sponsors routinely describe rejections selectively. The proposal is a standing commitment across ICH members to publish all negative decisions and their reasons within 30 days, indexed alongside approvals, so that other regulators can rely on negative as well as positive assessments and developers can learn what evidence was insufficient.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Regulatory divergence between regions): FDA Oncology Center of Excellence, Project Orbis","url":"https://www.fda.gov/about-fda/oncology-center-excellence/project-orbis"}],"tags":[],"related":["fda-approvals"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-regulatory-fragmentation","b-negative-results"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Systematic publication of rejections reduces resubmissions with the same deficiency and reduces the number of products approved in one region after rejection in another for the same evidence package.","rationale":"Negative decisions carry as much information as positive ones and currently reach only the sponsor. Publication also deters approval shopping between jurisdictions.","test":"Analyse the first two years of published FDA CRLs for oncology to quantify the share disclosed accurately by sponsors beforehand; extend publication commitments through ICH and monitor resubmission patterns.","maturity":"early-clinical","actor":"regulator","cost":"small","horizonYears":2},{"id":"idea-tr1-public-trial-cost-benchmarks","kind":"idea","name":"Publish per-patient trial cost benchmarks and target halving them","aka":[],"tldr":"Nobody knows what a cancer trial should cost because budgets are secret. Publishing anonymised cost per patient by trial type would expose waste and let funders set targets.","summary":"Sponsors and sites contribute anonymised per-patient cost data by phase, design and procedure to an independent benchmark (as hospitals do for procedure costs), broken down into drug, monitoring, imaging, data management and site payments. Funders set cost-per-patient targets for public trials and require justification above the benchmark.","asOf":"2026-09-08","links":[{"label":"Clinical Trials Transformation Initiative","url":"https://ctti-clinicaltrials.org/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["nci","cruk"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-design","b-funding-allocation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Transparency plus targets will reduce the median cost per patient of publicly funded phase 3 oncology trials by a third within five years without loss of data quality.","rationale":"Cost varies severalfold for similar trials; most of the excess is monitoring, imaging frequency and site overhead that add no information. Benchmarking drove cost convergence in construction and hospital procedures.","test":"Pilot the benchmark across two cooperative groups and one sponsor; compare cost dispersion and median cost before and after publication.","maturity":"speculative","actor":"policy","cost":"small","horizonYears":3},{"id":"idea-tr2-bicr-discordance-public","kind":"idea","name":"Publish the disagreement between trial doctors and independent reviewers for every trial","aka":[],"tldr":"Trials often have independent radiologists check whether tumours grew. How often they disagree with the treating doctors is a measure of how trustworthy the result is, and it is rarely published.","summary":"Blinded independent central review (BICR) is standard for progression-free survival in registrational trials, and discordance with investigator assessment is common. Regulators see the discordance data; the public usually does not. Requiring publication of the discordance rate, its direction by arm, and the sensitivity analysis in every trial report would let readers assess bias, and would create a dataset on when BICR matters and when it can be dropped to save cost.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Biomarkers are not validated or standardised): Fernandez et al., Examination of low ERBB2 protein expression in breast cancer tissue (JAMA Oncology 2022)","url":"https://doi.org/10.1001/jamaoncol.2021.7239"}],"tags":[],"related":["idea-tr2-automated-stats-check"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["recist","pfs","hazard-ratio"],"trials":[],"people":[],"bottlenecks":["b-biomarker-validation","b-trial-design"],"keyPapers":["paper-fernandez-jama-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Systematic publication will show that differential discordance (favouring the experimental arm) is present in a minority of open-label trials but is concentrated in trials with small effect sizes, allowing targeted rather than universal BICR.","rationale":"Meta-analyses of BICR versus investigator assessment suggest overall agreement in hazard ratios but with informative exceptions; hiding the data prevents learning which trials are at risk.","test":"Adopt as a reporting requirement in journal and regulatory guidance; analyse the first 100 trials reporting discordance.","maturity":"early-clinical","actor":"regulator","cost":"small","horizonYears":1},{"id":"idea-lung-uk-screening-testing-and-access-gaps","kind":"idea","name":"Publish the four numbers the NHS lung cancer pathway does not currently measure: reflex testing rate, genomic turnaround, surgical access and a lung-specific waiting time in every nation","aka":[],"tldr":"Every targeted result on this roadmap depends on a test happening fast enough to act on. In England nobody publishes what share of lung cancers are tested, how long the test takes, or, in Wales and Northern Ireland, how long the lung pathway takes at all.","summary":"The United Kingdom and NHS page for lung cancer set out to record what the NHS delivers against what the evidence says, and four of its findings are absences rather than figures.\n\nThe first is the reflex testing rate. A full-text search of the National Lung Cancer Audit's State of the Nation 2026 report for EGFR, ALK, ROS1, PD-L1, molecular, genomic and biomarker returns a single hit, in a recommendation asking trusts to ensure molecular pathology capacity. No published figure says what proportion of English lung cancer patients receive the testing NICE NG122 requires before treatment.\n\nThe second is turnaround. The National Genomic Test Directory has no turnaround column, and NHS England's genomic testing activity release says waiting-time data is planned for a future publication. The newest figures anyone can quote are from the 2019 GIRFT and audit organisational survey and an audit spotlight on people diagnosed in 2017.\n\nThe third is who gets an operation. No NHS England document names the thoracic surgery centres: service specification 170016/S sets the volume rules and says there were 29 units in England when it was written, lists none of them, and has not been refreshed since July 2017. The centre list on the UK page is assembled from the audit's resection counts instead.\n\nThe fourth is time. Wales reports its suspected cancer pathway for all cancers together, with no lung-specific figure; Northern Ireland publishes no 28-day faster diagnosis standard and splits lung out only for the 31-day one.\n\nThe proposal is that the four be published, on the same cycle as the audit, so that the pathway can be measured where it actually breaks.","asOf":"2026-09-25","links":[],"tags":["lung-evidence"],"related":["idea-prev-mobile-lung-screening-deprived-areas","diagnostics-roadmap","lung-cancer-evidence-roadmap"],"cancers":["lung-cancer","nsclc","sclc"],"sections":["early-detection","diagnostics"],"technologies":["ngs","liquid-biopsy"],"targets":[],"drugs":[],"companies":[],"institutions":["nice"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-early-detection","b-care-fragmentation","b-workforce","b-global-access","b-drug-pricing"],"keyPapers":["paper-uspstf-lung-cancer-screening-jama-2021","paper-forrest-socioeconomic-inequalities-lung-cancer-treatment-plos-med-2013","paper-sequist-genotypic-histological-evolution-egfr-resistance-sci-transl-med-2011"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Publishing reflex molecular testing rates, genomic turnaround times, named thoracic surgery centres and a lung-specific waiting time for all four nations would show variation between trusts and nations large enough to explain part of the treatment gap the same audit already measures by deprivation, and would move it, as publishing surgical resection rates did.","rationale":"The audit already measures the outcomes these four inputs decide: the proportion given treatment with curative intent, the proportion having surgery, and the time from diagnosis to treatment. It does not measure the inputs. A target-driven drug on this roadmap is worthless to a patient whose tumour was never genotyped, and no one can say how often that happens. The precedent is the audit's own surgical resection rate, which was published, varied, and then rose.","test":"Add three fields to the National Lung Cancer Audit's annual return (was a molecular panel requested, when was the result available, and which alterations were tested) and one to the NHS England genomic testing activity release (request to report turnaround by test and by laboratory hub); refresh service specification 170016/S with the units it governs; and have Wales and Northern Ireland report lung separately against the same standards England uses. Success is that each figure exists, is broken down by trust or health board, and can be put beside the audit's curative-intent and surgery rates.","maturity":"speculative","actor":"policy","cost":"medium","horizonYears":5},{"id":"idea-tr1-public-screen-fail-reasons","kind":"idea","name":"Publish why patients were screened out of each trial","aka":[],"tldr":"Trials record why each screened patient did not join, but that data is never shared. Publishing it would show which rules block the most people and which are pointless.","summary":"Sponsors report, per trial, the number screened, the number enrolled and screen-failure reasons in a standard coded vocabulary (specific criterion, patient declined, logistics) to the trial registry at completion. Aggregate analysis identifies criteria that exclude many patients across trials with no safety justification and informs eligibility reform.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Trials enrol too few, too slowly): Unger et al., Systematic review of barriers to cancer trial participation (JNCI 2019)","url":"https://doi.org/10.1093/jnci/djy221"}],"tags":[],"related":["clinicaltrials-gov","eudract-ctis"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-enrolment","b-trial-design"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Public screen-failure reporting will identify a small set of criteria responsible for the majority of exclusions in each disease and lead to their removal in subsequent protocols, increasing eligible fractions.","rationale":"Eligibility reform currently relies on simulations against real-world data; actual screen-failure data is the ground truth and already collected on screening logs. Making it visible creates pressure to fix the worst criteria.","test":"A registry pilots a screen-failure data field for oncology trials; after two years, analyse which criteria dominate and whether protocols from participating sponsors changed.","maturity":"speculative","actor":"regulator","cost":"small","horizonYears":2},{"id":"idea-bio2-whole-genome-mrd-depth","kind":"idea","name":"Push residual disease detection a hundredfold deeper with whole-genome methods","aka":[],"tldr":"Current blood tests for leftover cancer track a few dozen mutations and miss low-level disease. Whole-genome and error-corrected methods integrate signal across thousands of tumour-specific sites plus methylation and fragment features, reaching detection near one part per million in research settings; cost, turnaround and reproducibility are the barriers.","summary":"Whole-genome and error-corrected duplex approaches integrate signal across thousands to millions of tumour-specific sites, plus fragmentomic and methylation features, reaching detection limits reported near one part per million in research settings. Cost, turnaround and bioinformatics reproducibility are the barriers, not biology. If the limit of detection falls by two orders of magnitude, ctDNA-negative results become genuinely informative.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Dormant cells and minimal residual disease): Tie et al., ctDNA analysis guiding adjuvant therapy in stage II colon cancer (NEJM 2022)","url":"https://doi.org/10.1056/NEJMoa2200075"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["mrd-testing","liquid-biopsy","fragmentomics","methylation-profiling","wes-wgs"],"targets":[],"drugs":[],"companies":["foresight-diagnostics","delfi-diagnostics","personalis"],"institutions":[],"pathways":[],"terms":["ctdna","mrd","vaf"],"trials":[],"people":[],"bottlenecks":["b-dormancy-mrd","b-early-detection","b-biomarker-validation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Genome-wide MRD detection lowers the limit of detection by at least fiftyfold versus fixed panels, raising sensitivity for relapse at the six-month landmark above 90% while keeping specificity above 99%.","rationale":"Signal integration across many loci is a statistical rather than chemical improvement, so it scales with sequencing cost, which continues to fall. The same logic transformed non-invasive prenatal testing.","test":"Retrospective head-to-head on banked serial plasma from an adjuvant cohort with known outcomes, comparing panel and genome-wide assays on identical samples; then prospective validation within an MRD platform.","maturity":"early-clinical","actor":"data","cost":"medium","horizonYears":4},{"id":"idea-rejuv-biological-age-as-a-randomised-endpoint","kind":"idea","name":"Put a biological-age marker in a trial that also measures something a person would notice","aka":[],"tldr":"Epigenetic clocks and senescence markers run fast after cancer treatment, and nobody has shown that moving one matters. The way to find out is to make the clock a secondary endpoint in a trial whose primary endpoint is physical function.","summary":"The measurement side of biological ageing in survivors is in reasonable shape. The intervention side is empty, and the market filling it is not. The design problem is that a trial with a clock as its primary endpoint proves nothing a person would notice, while a trial with a clinical endpoint is expensive, so neither gets run and the question stays open.\n\nThe resolution is to stop choosing. Any adequately powered randomised trial of an intervention in survivors should bank samples and prespecify a biological-age secondary analysis: does the marker move, and does movement in the marker track movement in the function endpoint within the same people? Answer that a few times and the field learns whether these markers are worth using as endpoints at all, which is the question that currently blocks every geroprotective trial in oncology.\n\nPROFFi is the first trial with this shape in cancer survivors: fisetin with and without tailored exercise, four arms, with change in six-minute walk distance as the primary endpoint. The cheapest version of this idea is a funder requirement rather than a new trial, attached to the survivorship trials already being paid for.","asOf":"2026-10-02","links":[{"label":"Qin et al., Epigenetic age acceleration and chronic health conditions among adult survivors of childhood cancer (JNCI 2021;113:597-605)","url":"https://doi.org/10.1093/jnci/djaa147"},{"label":"Ness et al., Physiologic frailty as a sign of accelerated aging among adult survivors of childhood cancer: a report from the St Jude Lifetime cohort study (JCO 2013;31:4496-4503)","url":"https://doi.org/10.1200/JCO.2013.52.2268"},{"label":"ClinicalTrials.gov NCT06113016","url":"https://clinicaltrials.gov/study/NCT06113016"}],"tags":["rejuvenation","survivorship","open-problem","biological-ageing"],"related":["rejuv-age-epigenetic-clocks","rejuv-age-senescent-cells-after-treatment","rejuv-frontier-senolytics","rejuv-frontier-what-works","rejuv-trial-proffi","rejuvenation-roadmap"],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["rejuv-agenda-biological-age-as-an-untested-target","b-biomarker-validation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"If markers of biological ageing are worth treating, change in them will correlate with change in physical function within randomised participants; if it does not, the markers are descriptive and should not be used as endpoints.","rationale":"No clock is validated as a clinical test, none is used to make a treatment decision, and no trial has shown that moving a clock changes what happens to a person. The same holds for p16INK4a and for telomere length. Meanwhile senolytics, metformin, rapamycin and NAD+ precursors are all sold or discussed for this purpose with no randomised evidence in survivors, and the trial designed to test metformin as a geroprotector has not started after a decade.","test":"Prespecify biological-age secondary endpoints, with banked samples, in every publicly funded randomised trial of exercise, rehabilitation or a candidate geroprotective agent in cancer survivors, and pool them. Read out whether within-person change in marker tracks within-person change in the function primary.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":6},{"id":"idea-prev-cytisine-essential-medicine","kind":"idea","name":"Put cytisine, a cheap plant-based quit-smoking pill, on every essential medicines list","aka":[],"tldr":"Cytisine costs a few dollars per course and works about as well as varenicline, but is unavailable in most countries. Global approval and procurement would make quitting affordable.","summary":"Cytisine costs a few dollars per course and works about as well as varenicline, but is unavailable in most countries, so this idea seeks WHO Essential Medicines listing, WHO prequalification and pooled procurement for low- and middle-income countries. Cytisinicline has randomised evidence of efficacy from the ORCA trials and decades of use in Eastern Europe; cost is the barrier to pharmacotherapy in poorer countries, and cytisine removes it. The aim is a several-fold rise in pharmacotherapy-assisted quit attempts. The test is a procurement pilot in three countries with quit-attempt monitoring. Being tested at scale, it addresses the bottlenecks Prevention we already have is not deployed and Most of the world has almost no cancer care.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Prevention we already have is not deployed): Islami et al., Proportion of cancer attributable to modifiable risk factors (CA 2018)","url":"https://doi.org/10.3322/caac.21440"}],"tags":[],"related":[],"cancers":["nsclc"],"sections":["prevention"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption","b-global-access"],"keyPapers":["paper-islami-ca-cancer-j-clin"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Availability of cytisine at under $10 per course increases pharmacotherapy-assisted quit attempts in low- and middle-income countries five-fold.","rationale":"Cost is the barrier to pharmacotherapy in poorer countries; cytisine removes it.","test":"Run a procurement pilot in three countries with quit-attempt monitoring.","maturity":"being-tested-at-scale","actor":"policy","cost":"small","horizonYears":3},{"id":"idea-acc-essential-palliative-package-in-uhc","kind":"idea","name":"Put the essential palliative care package into every universal health coverage benefit list","aka":[],"tldr":"The Lancet Commission defined a cheap basic package of drugs, equipment and staff for palliative care. Countries expanding health coverage should include it as a guaranteed benefit.","summary":"The Lancet Commission on Global Access to Palliative Care and Pain Relief specified an Essential Package (a short list of medicines including oral morphine, basic equipment, and human resources) costed at a few dollars per capita in low-income countries. Countries designing universal health coverage benefit packages routinely omit palliative care. Advocacy and technical assistance to include the package as a defined entitlement would make funding and delivery accountable.","asOf":"2026-09-08","links":[{"label":"Lancet Commission on palliative care and pain relief","url":"https://www.thelancet.com/commissions/palliative-care"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-palliative","b-global-access","b-funding-allocation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Countries adding the Essential Package to their benefit lists will show increased morphine availability at district level and higher palliative care coverage within three years compared with countries that do not.","rationale":"Benefit-package inclusion is how services move from charity to entitlement; the package is defined, costed, and endorsed.","test":"Track adoption across countries revising benefit packages, with availability audits and coverage estimates before and after inclusion.","maturity":"speculative","actor":"policy","cost":"medium","horizonYears":4},{"id":"idea-bio2-cachexia-function-endpoint","kind":"idea","name":"Qualify a physical function endpoint so anti-wasting drugs can be approved","aka":[],"tldr":"Regulators are unsure what to accept as proof that an anti-wasting drug helps. Agreeing on a simple measure such as stair climbing would unblock the whole field.","summary":"Cachexia drug development has repeatedly stalled on endpoint uncertainty: weight is easy but not clearly meaningful, and composite quality-of-life measures are noisy. Candidate function measures (stair climb power, six-minute walk, handgrip strength, wearable-derived daily step count) are simple and reproducible but not formally qualified. A qualification programme with pre-competitive data pooling would create a defined path.","asOf":"2026-09-08","links":[{"label":"FDA Oncology Center of Excellence (page moved; nearest live section)","url":"https://www.fda.gov/about-fda/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["exercise-oncology","geriatric-assessment"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-cachexia-supportive","b-trial-design","b-patient-voice"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A qualified function endpoint, anchored to patient-reported meaningfulness, lets a cachexia trial of about 300 patients demonstrate benefit convincingly, and at least three sponsors initiate registrational trials within three years of qualification.","rationale":"Endpoint qualification unlocked development in Duchenne muscular dystrophy, idiopathic pulmonary fibrosis and heart failure. Cachexia has more patients than all of those and one approved drug in most of the world.","test":"Pool individual-patient data from completed cachexia trials to establish the test-retest reliability and minimal clinically important difference of candidate measures; submit a qualification package.","maturity":"speculative","actor":"regulator","cost":"small","horizonYears":5},{"id":"idea-reg-ipsc-master-bank-qualified-once","kind":"idea","name":"Qualify one iPSC master cell bank once for many off-the-shelf cell products","aka":[],"tldr":"Cell therapies made from a single stem cell line could be produced in bulk. Regulators should let companies certify the parent cell line once rather than repeating it for every product.","summary":"Induced pluripotent stem cell-derived CAR-NK and CAR-T products (Fate, Century, Sana, Shoreline and others) start from a clonal, gene-edited master cell bank that can in principle yield thousands of doses per run. Today each product's regulatory file repeats the characterisation of the bank (genomic stability, tumourigenicity, identity, adventitious agents). The proposal is a 'qualified master bank' status: a hypoimmune-edited iPSC bank characterised once to an agreed standard and cross-referenced by any product derived from it, with only the differentiation and CAR-specific data submitted per product.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Manufacturing cost and time for living and radioactive medicines): Hernandez, Prasad & Gellad, Total costs of chimeric antigen receptor T-cell immunotherapy (JAMA Oncology 2018)","url":"https://doi.org/10.1001/jamaoncol.2018.0977"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["allogeneic-cell-therapy","car-nk-macrophage"],"targets":[],"drugs":[],"companies":["fate-therapeutics","sana-biotechnology"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-manufacturing-cell-therapy"],"keyPapers":["paper-hernandez-jama-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Qualified-bank status cuts the CMC section of an iPSC-derived product IND by at least half and the time from candidate selection to first-in-human by a year, while enabling a cost of goods per dose below $5,000 at scale.","rationale":"Drug master files for excipients and platform designations for vectors already allow shared, referenced qualification. iPSC banks are the most expensive, most repeated component of the allogeneic pipeline and their characterisation is product-independent.","test":"FDA and EMA pilot a master-bank designation with two or three developers, publish the characterisation standard, and compare CMC review questions and timelines against conventional iPSC product INDs.","maturity":"early-clinical","actor":"regulator","cost":"medium","horizonYears":4},{"id":"idea-tr2-psma-volume-qualification","kind":"idea","name":"Qualify PSMA PET tumour volume as a validated imaging biomarker","aka":[],"tldr":"PSMA scans could measure prostate cancer burden and response far better than PSA, but no one has done the standardisation work to make the measurement trustworthy across scanners.","summary":"Total PSMA-positive tumour volume and SUV metrics predict outcome in metastatic prostate cancer and response to radioligand therapy, but acquisition, reconstruction and segmentation vary between centres. A QIBA-style profile (phantom calibration, harmonised reconstruction, validated segmentation software) followed by biomarker qualification for defined contexts of use (prognosis, response assessment) would let PSMA volume be used as an endpoint and selection tool in trials.","asOf":"2026-09-08","links":[{"label":"RSNA QIBA","url":"https://www.rsna.org/research/quantitative-imaging-biomarkers-alliance"}],"tags":[],"related":["psma-pet-to-rlt","idea-total-body-pet-dosimetry"],"cancers":["prostate"],"sections":[],"technologies":["psma-pet","pet-ct"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-biomarker-validation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Harmonised PSMA volumetric measurements will achieve test-retest and inter-site coefficient of variation under 15% and will predict overall survival on radioligand therapy better than PSA response.","rationale":"FDG PET response criteria (PERCIST, Deauville) needed the same standardisation before adoption; PSMA PET is now widespread enough to justify it.","test":"A multi-centre phantom and test-retest study followed by retrospective validation on trial imaging from VISION and PSMAfore, then a qualification submission.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":4},{"id":"idea-moon-quality-adjusted-survival-standard","kind":"idea","name":"Quality-adjusted survival reported in every trial publication and label","aka":[],"tldr":"Report how long patients lived well, not only how long they lived. Methods exist (Q-TWiST) but are rarely used.","summary":"Quality-adjusted time without symptoms or toxicity (Q-TWiST) and related methods partition survival into time with toxicity, time without progression or toxicity, and time after progression, weighted by patient utilities. They are validated and occasionally reported but not standard. The proposal is that CONSORT-style reporting guidance, journals and regulators require a quality-adjusted survival analysis for every phase 3 oncology trial, using patient-reported utilities collected in the trial.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Toxicity and quality of life are undervalued): Di Maio et al., Symptomatic toxicities experienced during anticancer treatment: agreement between patient and physician reporting (JCO 2015)","url":"https://doi.org/10.1200/JCO.2014.57.9334"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["os","hazard-ratio"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol","b-knowledge-diffusion"],"keyPapers":["paper-di-maio-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Routine quality-adjusted survival reporting changes the ranking of regimens in a meaningful minority of trials and is adopted by guideline committees within five years.","rationale":"The data required (toxicity dates, progression, survival, utilities) are already collected; the analysis is cheap and directly comparable across trials.","test":"Reanalyse fifty recent phase 3 trials for Q-TWiST and compare rankings against those by hazard ratio; survey guideline committees on the added value.","maturity":"early-clinical","actor":"research","cost":"small","horizonYears":2},{"id":"idea-moon-preference-studies-before-phase3","kind":"idea","name":"Quantitative patient preference studies set the benefit-risk bar before phase 3","aka":[],"tldr":"Before a big trial starts, ask hundreds of patients how much extra survival they would trade for a given side-effect, so the trial is designed to test something patients would actually want.","summary":"Discrete choice experiments and best-worst scaling quantify how patients trade benefits against harms and burdens. Regulators (FDA CDRH, EMA) have accepted such data in medical devices and some drugs. The proposal is that for each new indication, a preference study defines the minimum clinically important benefit and acceptable toxicity profile, which is then written into the phase 3 design and the regulatory review.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Patients lack understanding, navigation and agency): Basch et al., Overall survival results of a trial assessing patient-reported outcomes for symptom monitoring during routine cancer treatment (JAMA 2017)","url":"https://doi.org/10.1001/jama.2017.7156"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-patient-voice","b-trial-design"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Preference-informed designs produce approvals with higher patient-relevant value and fewer post-approval label restrictions, and shift phase 3 endpoints towards those with the highest patient weights.","rationale":"Minimum clinically important differences are currently set by convention and statistics; patients have measurable and heterogeneous preferences that should anchor them.","test":"Run preference studies in three tumour types with upcoming phase 3 programmes; compare the preference-derived benefit thresholds with those in current protocols and with eventual approval decisions.","maturity":"early-clinical","actor":"regulator","cost":"medium","horizonYears":4},{"id":"idea-moon-question-prompt-lists","kind":"idea","name":"Question prompt lists sent to patients before every major consultation","aka":[],"tldr":"Before a results or treatment-planning appointment, patients receive a list of good questions to ask, tailored to their situation, and can tick the ones they want covered.","summary":"Question prompt lists increase question-asking in randomised studies, particularly when clinicians endorse them. Portals can deliver tailored lists (stage, treatment intent, trial availability) automatically before scheduled visits, with the selected questions visible to the clinician. This is a cheap, scalable implementation of a proven tool that mostly fails through lack of delivery.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Patients lack understanding, navigation and agency): Basch et al., Overall survival results of a trial assessing patient-reported outcomes for symptom monitoring during routine cancer treatment (JAMA 2017)","url":"https://doi.org/10.1001/jama.2017.7156"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["randomised-trial"],"trials":[],"people":[],"bottlenecks":["b-patient-voice"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Automated tailored prompt lists increase the number of patient questions and the discussion of prognosis and trials, and reduce decisional conflict, without lengthening consultations by more than two minutes.","rationale":"The barrier is delivery, not evidence; visit scheduling systems know exactly when the list is needed.","test":"Portal-level A/B test across an oncology network measuring questions asked (audio-coded sample), decisional conflict and consultation length.","maturity":"being-tested-at-scale","actor":"clinic","cost":"small","horizonYears":1},{"id":"idea-moon-radiotherapy-for-everyone-2040","kind":"idea","name":"Radiotherapy for everyone who needs it by 2040","aka":[],"tldr":"Half of cancer patients need radiotherapy and most of the world cannot get it. Commit to low-cost machines, automated planning and trained staff so that access is universal by 2040.","summary":"The Lancet Oncology Commission estimated enormous unmet radiotherapy need in low- and middle-income countries, with many countries having no machine at all. Barriers are capital cost, maintenance, physics and oncologist workforce, and planning complexity. The proposal is a coordinated programme: purpose-designed low-cost, low-maintenance linear accelerators for harsh environments (the CERN-STFC-ICEC effort), AI-automated contouring and planning with remote quality assurance, task-shifted training curricula, and pooled procurement and financing through IAEA Rays of Hope and development banks, with a public dashboard of machines per million and treatment gap by country.","asOf":"2026-09-08","links":[{"label":"IAEA Rays of Hope","url":"https://www.iaea.org/services/rays-of-hope"}],"tags":[],"related":[],"cancers":["cervical","head-and-neck"],"sections":[],"technologies":["imrt-igrt","brachytherapy","sbrt"],"targets":[],"drugs":[],"companies":["varian","elekta"],"institutions":["iarc"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-global-access","b-workforce","b-surgery-radiation-innovation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"The programme halves the global radiotherapy treatment gap by 2035 and closes it in participating countries by 2040, with survival gains in cervical, head and neck and breast cancers measurable in registries.","rationale":"Radiotherapy is curative, cost-effective and needed in half of all patients; the constraints are engineering, finance and workforce, all of which have been solved for other technologies at scale.","test":"Deploy ruggedised machines with automated planning and remote QA in ten centres in five countries; measure uptime, throughput, plan quality against expert review and cost per course.","maturity":"early-clinical","actor":"policy","cost":"large","horizonYears":10},{"id":"idea-pdac-uk-active-treatment-rate-audit-and-target","kind":"idea","name":"Raise the share of UK patients who receive any active treatment, and publish it by trust","aka":[],"tldr":"In England and Wales a national audit now reports each year what share of people diagnosed with pancreatic cancer receive any treatment aimed at the cancer, how many are discussed by a specialist team and how many see a specialist nurse. The proposal is a national target for the treatment rate, published by hospital, so the trusts furthest behind are visible.","summary":"The National Pancreatic Cancer Audit, run by the National Cancer Audit Collaborating Centre, has published three State of the Nation reports (2024, covering patients diagnosed 2020 to 2021 in England and 2022 in Wales; 2025; and 2026, covering 2022 to 2023 in England and 2023 to 2024 in Wales), each with five recommendations, and reports performance indicators including multidisciplinary team discussion, clinical nurse specialist involvement, enzyme replacement prescribing and receipt of active treatment, with a data viewer for individual organisations. This is a placeholder for the gaps the UK and NHS page names in detail: the proportion receiving no active treatment, variation between trusts, the time from diagnosis to treatment, and the treatment rate in older and less fit patients. The idea is to attach a national target to the active treatment indicator, publish trust-level results with case-mix adjustment, and fund the multidisciplinary capacity (surgeons, oncologists, specialist nurses, dietitians) in the trusts below it. Pancreatic Cancer UK's campaigns (Don't Write Me Off; Unite Diagnose Save Lives 2025) make the same case.","asOf":"2026-09-24","links":[{"label":"NPaCA State of the Nation Report 2026","url":"https://www.natcan.org.uk/reports/npaca-state-of-the-nation-report-2026/"},{"label":"NPaCA State of the Nation Report 2025","url":"https://www.natcan.org.uk/reports/npaca-state-of-the-nation-report-2025/"},{"label":"NPaCA State of the Nation Report 2024","url":"https://www.natcan.org.uk/reports/npaca-state-of-the-nation-report-2024/"},{"label":"Pancreatic Cancer UK: Don't Write Me Off campaign","url":"https://www.pancreaticcancer.org.uk/get-involved/make-a-difference/join-our-campaigns/dont-write-me-off-impact/"}],"tags":["pancreatic-evidence"],"related":["idea-pdac-enzyme-replacement-prescribing-by-default","idea-pdac-uk-fast-track-diagnosis-to-treatment-pathway"],"cancers":["pancreatic"],"sections":["supportive-care"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-care-fragmentation","b-aging-comorbidity","b-knowledge-diffusion"],"keyPapers":["paper-roberts-pert-survival-pancreatic-cancer-pancreatology-2019"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Publishing case-mix-adjusted active treatment rates by trust with a national target raises the national rate by 10 percentage points within three years and narrows the interquartile range between trusts by half.","rationale":"Audit-driven publication has moved treatment rates in other UK cancers; the indicators, the data flow and the organisational comparisons already exist in the audit.","test":"Before-and-after comparison of the audit's active treatment indicator and its between-trust variation across the years following publication of a target, with case-mix adjustment; qualitative review of what the lowest trusts changed.","maturity":"speculative","actor":"policy","cost":"medium","horizonYears":4},{"id":"idea-tr2-random-audit","kind":"idea","name":"Random audits of published, funded research, like tax audits","aka":[],"tldr":"Funders should randomly select a small fraction of the papers they paid for and check the raw data, analysis and records, with public results. The possibility of an audit changes behaviour.","summary":"Research misconduct investigations are triggered by complaints, which is slow and rare. Randomly selecting 1 to 2% of funded publications per year for a data and records audit (raw data availability, analysis reproducibility, image integrity, cell-line and reagent documentation), carried out by an independent office with published aggregate results, would create a deterrent and an evidence base on the prevalence of problems.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Preclinical results do not reproduce): Errington et al., Investigating the replicability of preclinical cancer biology (eLife 2021)","url":"https://doi.org/10.7554/eLife.71601"}],"tags":[],"related":["idea-tr2-raw-image-deposit","idea-tr2-data-link-enforcement"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-reproducibility"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Audits will find serious reproducibility or integrity problems in at least 5% of sampled papers, and adopting funders will see this rate fall by half over five years.","rationale":"Random audits deter tax evasion at low audit rates because the expected cost of detection is high; the same logic applies to research where career consequences are severe.","test":"One funder audits 100 randomly selected funded oncology papers per year; publish aggregate findings and track the rate.","maturity":"speculative","actor":"philanthropy","cost":"medium","horizonYears":2},{"id":"idea-reg-antihistamine-plus-io-trial","kind":"idea","name":"Randomise a cheap antihistamine alongside immunotherapy","aka":[],"tldr":"Patients who happened to take common allergy pills during immunotherapy seemed to live longer in a large records study. A simple randomised trial would show whether the pills really help.","summary":"A 2022 analysis of MD Anderson records (Li and colleagues, Cancer Cell) found that H1-antihistamine use during checkpoint inhibitor therapy was associated with improved survival in melanoma and lung cancer, with mechanistic work suggesting histamine-HRH1 signalling in macrophages drives T-cell dysfunction. Antihistamines cost pennies and are extremely safe. The proposal is a placebo-controlled randomised trial of a non-sedating H1-antihistamine (for example fexofenadine or loratadine) added to standard checkpoint inhibitor therapy in non-small cell lung cancer, with a plasma histamine biomarker sub-study.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (No incentive to repurpose cheap drugs): Pantziarka et al., The Repurposing Drugs in Oncology (ReDO) Project (ecancer 2014)","url":"https://doi.org/10.3332/ecancer.2014.442"}],"tags":[],"related":[],"cancers":["nsclc","melanoma"],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":[],"drugs":["pembrolizumab"],"companies":[],"institutions":["md-anderson"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-generic-repurposing","b-immunotherapy-response"],"keyPapers":["paper-keynote-189-nejm-2018","paper-pantziarka-ecancermedicalscience"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Adding an H1-antihistamine to first-line checkpoint inhibitor therapy improves progression-free survival with a hazard ratio of 0.8 or better, with the effect concentrated in patients with high plasma histamine.","rationale":"The observational effect size was large, a mechanism has been demonstrated in mice, and the intervention has essentially no cost or toxicity, making the expected value of a trial very high even at modest prior probability.","test":"Phase 2/3 randomised double-blind trial of roughly 600 patients with NSCLC starting pembrolizumab-based therapy, PFS primary endpoint, biomarker-stratified analysis.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":4},{"id":"idea-tr1-randomised-dose-comparison-before-pivotal","kind":"idea","name":"Randomise at least two doses in phase 2 before any pivotal trial","aka":[],"tldr":"Cancer drugs are usually tested at the highest dose patients can stand, and that dose sticks for life. Comparing two or more doses head-to-head before the big trial would find doses that work as well with fewer side effects.","summary":"Following FDA's Project Optimus, sponsors run randomised parallel-dose cohorts (typically two or three doses spanning the exposure-response range) in phase 2 with efficacy, tolerability and PK endpoints, before selecting the dose for registrational trials. Precedent: the post-approval randomised comparison of sotorasib 960 mg versus 240 mg, which found similar efficacy. The proposal makes randomised dose comparison the expectation, with regulators declining to accept single-dose pivotal trials for targeted agents without it.","asOf":"2026-09-08","links":[{"label":"FDA Oncology Center of Excellence: Project Optimus","url":"https://www.fda.gov/about-fda/oncology-center-excellence/project-optimus"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["kinase-inhibitors"],"targets":[],"drugs":["sotorasib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-dose-optimisation","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Agents with randomised dose comparison will be approved at lower doses than their maximum tolerated dose in a substantial fraction of cases, with lower rates of dose reduction and discontinuation in real-world use, and without loss of efficacy.","rationale":"Targeted agents and biologics often plateau in efficacy well below the maximum tolerated dose; MTD-based dosing is a legacy of cytotoxics. Dose reductions after approval are frequent and costly.","test":"Compare real-world dose-reduction and discontinuation rates for agents approved after randomised dose comparison versus contemporaneous agents approved at MTD.","maturity":"being-tested-at-scale","actor":"regulator","cost":"medium","horizonYears":3},{"id":"idea-tr1-registry-embedded-randomisation","kind":"idea","name":"Randomise inside the cancer registry: registry-based trials for everyday questions","aka":[],"tldr":"National cancer registries already collect the outcome data. Adding a randomisation button lets doctors compare two standard treatments across thousands of patients at a fraction of the usual cost.","summary":"Registry-based randomised trials, pioneered in cardiology by Sweden's TASTE trial, embed randomisation in a clinical quality registry and use routinely collected outcomes (death, recurrence, hospitalisation) as endpoints. Oncology registries in the Nordic countries, the Netherlands, the UK and some US states could support comparisons of approved treatments, schedules and follow-up strategies at a marginal cost per patient of a few hundred dollars.","asOf":"2026-09-08","links":[{"label":"TASTE registry-based randomised trial (NEJM 2013)","url":"https://www.nejm.org/doi/full/10.1056/NEJMoa1308789"}],"tags":[],"related":["seer"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["karolinska","nki"],"pathways":[],"terms":["real-world-evidence","standard-of-care"],"trials":[],"people":[],"bottlenecks":["b-trial-enrolment","b-trial-design","b-real-world-evidence"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Registry-embedded randomised trials in oncology can enrol at least ten times more patients per year per dollar than conventional pragmatic trials and answer comparative questions (sequence, schedule, duration, surveillance) that industry will not fund.","rationale":"TASTE randomised over 7,000 patients at low cost and produced a definitive answer. Oncology registries have the same coverage in several countries; the barriers are governance and consent design rather than technology.","test":"Run one registry-embedded trial of a surveillance or schedule question (e.g., follow-up imaging frequency after curative resection) in a national registry and report cost per patient, accrual rate and data completeness.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":4},{"id":"idea-bio2-registry-embedded-randomisation","kind":"idea","name":"Randomise inside the registry that already follows every patient","aka":[],"tldr":"Rare cancer patients are already tracked in registries. Offering randomisation inside the registry makes trials far cheaper and lets almost anyone take part.","summary":"Trials within cohorts, or registry-based randomised trials, use existing registry infrastructure for identification, consent, allocation and outcome capture, and have been used successfully in cardiology at a fraction of conventional trial cost. Rare cancers are ideal candidates because registries already exist, populations are dispersed, and conventional site-based trials cannot reach enough patients.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Rare and paediatric cancers without markets): Gatta et al., Rare cancers are not so rare: the rare cancer burden in Europe (EJC 2011)","url":"https://doi.org/10.1016/j.ejca.2011.08.008"}],"tags":[],"related":["seer","clinicaltrials-gov","genie"],"cancers":["sarcoma","neuroendocrine","thyroid"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["real-world-evidence","basket-umbrella-platform"],"trials":[],"people":[],"bottlenecks":["b-rare-cancers","b-trial-design","b-real-world-evidence"],"keyPapers":["paper-gatta-eur-j-cancer"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Registry-based randomisation reduces cost per randomised patient by an order of magnitude versus conventional rare cancer trials, while achieving acceptable data completeness and regulatory-grade outcome ascertainment.","rationale":"Registry-randomised trials in interventional cardiology showed that outcome capture through linked national data can be as reliable as bespoke case report forms. The infrastructure cost is already sunk in the registry.","test":"Run one registry-randomised comparison of two standard-of-care options in a rare cancer, reporting cost per patient, data completeness and regulator or guideline acceptance of the result.","maturity":"early-clinical","actor":"data","cost":"medium","horizonYears":5},{"id":"idea-crc-organ-preservation-randomised-in-pmmr-rectal","kind":"idea","name":"Randomise organ preservation against surgery in mismatch repair-proficient rectal cancer, with bowel function as a co-primary endpoint","aka":[],"tldr":"Half of rectal cancer patients given all their chemotherapy and radiotherapy first can keep their rectum. Nobody has ever randomised that against having the operation, so the trade-off between avoiding a stoma and the risk of the cancer regrowing is still guesswork.","summary":"Habr-Gama watched 71 of 265 patients whose rectal cancers vanished after chemoradiotherapy and reported ten-year overall survival of 97.7 percent across the series; OPRA made the strategy plannable, with three-year survival free of total mesorectal excision of 53 percent after consolidation chemotherapy and disease-free survival matching the 75 percent historical rate. In mismatch repair-deficient disease the question has been answered emphatically: every one of 49 rectal cancers treated with six months of dostarlimab had a clinical complete response, 82 of 103 patients across both Cercek cohorts avoided surgery, and two-year recurrence-free survival was 92 percent.\n\nFor the mismatch repair-proficient 90 percent, the evidence remains single-arm or historically controlled. OPRA's comparison is against historical data; regrowth continues beyond three years; and the assumption that salvage surgery after regrowth costs nothing rests on subgroup comparisons within the same non-randomised cohort. Meanwhile the thing patients actually weigh, long-term bowel, urinary and sexual function after watch and wait against after total mesorectal excision, has never been a primary endpoint.","asOf":"2026-09-24","links":[{"label":"Garcia-Aguilar et al.: OPRA (J Clin Oncol 2022)","url":"https://europepmc.org/article/MED/35483010"},{"label":"Cercek et al.: nonoperative management of mismatch repair-deficient tumours (N Engl J Med 2025)","url":"https://europepmc.org/article/MED/40293177"},{"label":"ClinicalTrials.gov NCT05610163","url":"https://clinicaltrials.gov/study/NCT05610163"}],"tags":["colorectal-evidence"],"related":["colorectal-roadmap","surgery-roadmap"],"cancers":["colorectal","rectal-cancer"],"sections":["surgery","radiation"],"technologies":["radiotherapy","mri","imrt-igrt","robotic-surgery"],"targets":[],"drugs":["folfox","capox","capecitabine","dostarlimab"],"companies":[],"institutions":[],"pathways":[],"terms":["organ-preservation","clinical-complete-response","total-neoadjuvant-therapy","total-mesorectal-excision"],"trials":["opra","rapido","prodige-23","azur-1"],"people":["julio-garcia-aguilar","andrea-cercek","angelita-habr-gama"],"bottlenecks":["b-surgery-radiation-innovation","b-toxicity-qol","b-trial-design"],"keyPapers":["paper-garcia-aguilar-opra-organ-preservation-jco-2022","paper-habr-gama-nonoperative-stage-0-rectal-ann-surg-2004","paper-cercek-nonoperative-management-mismatch-repair-deficient-tumours-nejm-2025","paper-bahadoer-rapido-short-course-radiotherapy-lancet-oncol-2021"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"In mismatch repair-proficient locally advanced rectal cancer with a clinical complete response after total neoadjuvant therapy, watch and wait is non-inferior to immediate total mesorectal excision for five-year disease-free survival and superior for patient-reported bowel function at two years.","rationale":"Organ preservation is already offered outside trials on the strength of OPRA and the international watch-and-wait registry, so the randomised comparison is becoming harder to run each year; and the function benefit that justifies the strategy has never been measured against the comparator it replaces.","test":"A randomised non-inferiority trial in patients with a clinical complete response after total neoadjuvant therapy, stratified by response assessment method, with five-year disease-free survival and two-year patient-reported bowel function as co-primary endpoints, MRI and endoscopic restaging centrally reviewed, and stoma-free survival, local regrowth and salvage resection rates reported as secondary outcomes. JANUS and the running total neoadjuvant therapy trials supply the platform.","maturity":"being-tested-at-scale","actor":"research","cost":"large","horizonYears":6},{"id":"idea-bio1-pre-randomised-sequencing-trials","kind":"idea","name":"Randomise the next line of treatment before the first one fails","aka":[],"tldr":"Trials usually study one treatment at a time, so nobody knows the best order. Deciding the next step in advance, by lottery, answers the sequencing question at little extra cost.","summary":"Sequencing questions are almost never answered because patients leave the trial at progression. A pre-randomised design assigns the second-line option at the time of first-line enrolment, keeps patients within the protocol at progression, and collects the progression biopsy. Total sample size increases modestly, but the design yields a real strategy comparison rather than isolated line-by-line results.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Acquired resistance to every therapy): Soria et al., Osimertinib in untreated EGFR-mutated NSCLC (FLAURA, NEJM 2018)","url":"https://doi.org/10.1056/NEJMoa1713137"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["adc-sequencing","os"],"trials":[],"people":[],"bottlenecks":["b-resistance","b-trial-design"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Strategy-randomised sequencing trials detect clinically meaningful differences in overall survival between drug orders that line-by-line trials cannot detect, in at least one common setting.","rationale":"Overall survival depends on the whole sequence, not the first agent; oncology has repeatedly discovered that ordering matters (for example in metastatic colorectal and prostate cancer) only through retrospective analysis.","test":"Add pre-randomised second-line assignment to two ongoing first-line trials and compare information gained per patient with a matched conventional design.","maturity":"speculative","actor":"research","cost":"medium","horizonYears":6},{"id":"idea-prostate-randomise-the-sequence-not-only-the-drugs","kind":"idea","name":"Randomise the order of treatment, not only the drugs: a strategy platform for metastatic prostate cancer","aka":["sequencing trial prostate cancer","PFS2 strategy trial","treatment order randomised prostate"],"tldr":"Metastatic prostate cancer now has six classes of treatment that work, and no trial has ever compared the orders they can be given in. Every trial adds a drug to the front; none asks what should follow it, so the sequence a man receives is decided by habit and by what was licensed first.","summary":"Each of the classes was licensed against placebo or against an older drug, in a population defined by what it had already received: docetaxel against mitoxantrone, cabazitaxel after docetaxel, abiraterone and enzalutamide before and after chemotherapy, radium-223 in bone-predominant disease, lutetium-177 PSMA-617 after an androgen receptor drug and a taxane, and PARP inhibitors after progression on an androgen receptor drug. Intensification trials then moved several of them to the first day of metastatic diagnosis. What no trial has done is randomise the order.\n\nThat the order matters is not speculation. TRANSFORMER found identical progression-free survival on its primary endpoint and a difference of 8.6 months in progression-free survival through crossover depending on which arm came first, with a hazard ratio of 0.44. The same trial found prostate-specific antigen progression-free survival on enzalutamide was 3.8 months when it followed abiraterone and 10.9 months when it followed bipolar androgen therapy. CARD showed that switching from one androgen receptor drug to the other is worse than moving to cabazitaxel. The proposal is a standing platform in which the randomisation unit is a strategy rather than an agent, with progression-free survival through the second line as a co-primary endpoint alongside overall survival, and with re-randomisation at each progression. ProBio, which randomises by biomarker signature and adapts on outcome, is the nearest existing design; STAMPEDE2 has the infrastructure.\n\nWhat any of this means for someone treated in Britain, from the screening committee's position and the NICE appraisals to scanner and radiotherapy capacity, waiting times and how to reach a trial, is on the UK and NHS pathway page for prostate cancer.","asOf":"2026-09-25","links":[],"tags":["prostate-evidence"],"related":["idea-tr1-standing-platform-per-cancer","idea-tr1-smart-designs-for-adaptive-strategies","idea-bio1-alternating-schedules","prostate-roadmap","trial-modernisation-roadmap"],"cancers":["prostate","prostate-mhspc","prostate-mcrpc"],"sections":["hormonal","chemotherapy","radiopharma","targeted-therapy"],"technologies":["radioligand-therapy","psma-pet"],"targets":[],"drugs":["abiraterone","enzalutamide","docetaxel","cabazitaxel","pluvicto","radium-223","olaparib"],"companies":[],"institutions":[],"pathways":[],"terms":["radiographic-progression-free-survival","metastasis-free-survival","bipolar-androgen-therapy"],"trials":[],"people":[],"bottlenecks":["b-trial-design","b-combination-space","b-incentive-misalignment","b-funding-allocation","b-resistance"],"keyPapers":["paper-denmeade-transformer-bipolar-androgen-therapy-jco-2021","paper-de-bono-tropic-cabazitaxel-lancet-2010","paper-therap-lancet-2021","paper-vision-nejm-2021","paper-antonarakis-ar-v7-resistance-nejm-2014","paper-stampede-abiraterone-high-risk-attard-lancet-2022"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"In metastatic prostate cancer, the sequence in which the available treatment classes are given changes overall survival and time to the second progression by a margin comparable to that between the individual drugs, and a platform that randomises sequences with re-randomisation at progression can detect a difference of three months in progression-free survival through the second line within five years.","rationale":"Three lines of argument converge. Mechanistically, resistance to one androgen receptor drug is largely cross-resistance to the other, because both act on the ligand-binding domain and both select for AR-V7 and for lineage switching, whereas taxanes and radioligands do not; so an order that alternates mechanism should outlast one that does not. Empirically, TRANSFORMER measured a sequence effect of 8.6 months in PFS2 with quality of life favouring the same arm. Structurally, no regulator asks for sequence data and no company benefits from generating it, which is precisely the kind of question public platforms exist to answer. The alternative to running the trial is what happens now, which is that sequence is decided by licensing chronology.","test":"A publicly funded platform trial with sequence as the randomised unit: at metastatic castration-resistant progression, randomise between pre-specified two-step strategies (androgen receptor pathway inhibitor then taxane; taxane then androgen receptor pathway inhibitor; androgen receptor pathway inhibitor then radioligand where PSMA-positive; and in biomarker-positive men, PARP-containing strategies), with re-randomisation at the second progression. Co-primary endpoints: overall survival and progression-free survival through the second line. Stratify on homologous recombination repair status, PSMA uptake and prior hormone-sensitive intensification. Quality of life and time on treatment collected throughout. Five to seven years to first strategy comparison; reuse an existing platform rather than building new infrastructure.","maturity":"early-clinical","actor":"research","cost":"large","horizonYears":7},{"id":"lymphoma-ev-randomised-evidence-for-the-t-cell-lymphomas","kind":"idea","name":"Randomised evidence for the T-cell lymphomas, including the ones that are not in Europe or North America","aka":["Randomised trials in peripheral T-cell lymphoma","International trials for NK/T-cell and adult T-cell lymphoma"],"tldr":"Adult T-cell leukaemia has had one randomised trial, in 1998. Most T-cell lymphoma treatment rests on single-arm studies, and the diseases concentrated outside Europe and North America have the least evidence of all.","summary":"The obstacles are structural rather than scientific: no commercial sponsor for diseases concentrated in middle-income countries, regulatory fragmentation across the regions where the diseases occur, and the fact that a trial in a disease with 500 cases a year in any one country can only work internationally. The precedent is the international coordination that made paediatric leukaemia trials possible, which took decades and worked.","asOf":"2026-10-01","links":[],"tags":["lymphoma-evidence"],"related":["lymphoma-roadmap"],"cancers":["peripheral-t-cell-lymphoma","angioimmunoblastic-t-cell-lymphoma","cutaneous-t-cell-lymphoma","non-hodgkin-lymphoma"],"sections":["chemotherapy","immunotherapy"],"technologies":[],"targets":["cd30"],"drugs":["brentuximab-vedotin","asparaginase","cyclophosphamide","doxorubicin","vincristine","prednisone","etoposide"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["jcog9801","smile-enktl","echelon-2","alcanza"],"people":[],"bottlenecks":["b-rare-cancers","b-trial-enrolment","b-global-access","b-regulatory-fragmentation","b-incentive-misalignment"],"keyPapers":["paper-jcog9801-vcap-amp-vecp-adult-t-cell-leukaemia-jco-2007","paper-smile-chemotherapy-nk-t-cell-lymphoma-jco-2011","paper-horwitz-lancet"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Internationally coordinated randomised trials in the T-cell lymphomas, run where the diseases are concentrated, would change first-line standards that currently rest on single-arm series.","rationale":"JCOG9801 is the only randomised controlled trial ever run exclusively in adult T-cell leukaemia/lymphoma, with 118 patients, reported in 2007, and its three-year overall survival of 24 per cent in the better arm has not been improved on by a controlled comparison since. SMILE, the regimen that made extranodal NK/T-cell lymphoma treatable, is a 38-patient single-arm phase 2. ECHELON-2 and ALCANZA show that randomised trials in T-cell lymphoma are feasible and change practice when an industry sponsor has a reason to run them. The diseases without a sponsor have no trials.","test":"A standing international platform trial in peripheral T-cell lymphoma with disease-specific strata for adult T-cell leukaemia/lymphoma and extranodal NK/T-cell lymphoma, hosted in Japan, Korea, China, Brazil and the Caribbean as well as in Europe and North America, with a shared control arm and the statistical borrowing that makes rare-disease strata viable.","maturity":"speculative","actor":"policy","cost":"large","horizonYears":10},{"id":"idea-moon-post-approval-dose-deescalation","kind":"idea","name":"Randomised lower-dose trials for approved drugs with quality of life as the primary endpoint","aka":[],"tldr":"Many cancer drugs are approved at the highest dose patients could stand, not the best dose. Run trials that test lower doses on approved drugs and measure how patients feel.","summary":"Maximum tolerated dose remains the default for oral targeted agents and many antibody-drug conjugates; discontinuation for toxicity is common (abemaciclib, lenvatinib, cabozantinib, sotorasib). FDA Project Optimus addresses new drugs, not the existing catalogue. The proposal is a funded programme of post-marketing randomised non-inferiority trials of reduced or adaptive doses with patient-reported tolerability as primary and progression-free survival as a non-inferiority secondary, with regulators committed to label updates.","asOf":"2026-09-08","links":[{"label":"FDA Project Optimus","url":"https://www.fda.gov/about-fda/oncology-center-excellence/project-optimus"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":["abemaciclib","sotorasib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol","b-dose-optimisation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"For a majority of tested drugs, a lower or adaptive dose is non-inferior for progression-free survival and clearly superior for tolerability and adherence.","rationale":"Dose-response for many targeted drugs plateaus below the approved dose; sotorasib 240 mg versus 960 mg and several endocrine and kinase inhibitor examples support the pattern. Payers benefit directly.","test":"Payer-academic consortium funds five non-inferiority dose trials in the highest-spend drugs with known toxicity problems; readouts within four years.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":4},{"id":"idea-data-implementation-trials-programme","kind":"idea","name":"Randomised trials of how to spread proven cancer treatments, not just what works","aka":[],"tldr":"Fund proper trials of the methods used to get new evidence into practice (training, reminders, feedback, incentives), measured by whether patients actually receive the better treatment.","summary":"Implementation science in oncology is small and mostly observational. The proposal is a dedicated programme of cluster-randomised implementation trials, each testing strategies (audit and feedback, EHR defaults, champions, payment nudges) to accelerate uptake of a specific practice change, with structured-data outcomes and a common design so results generalise. NCI's Implementation Science programme is a base; the scale and randomisation are new.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Knowledge reaches practice too slowly): Morris, Wooding & Grant, The answer is 17 years, what is the question (JRSM 2011)","url":"https://doi.org/10.1258/jrsm.2011.110180"}],"tags":[],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["nci"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-knowledge-diffusion","b-funding-allocation"],"keyPapers":["paper-morris-j-r-soc-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A portfolio of implementation trials will identify strategies that halve the time to majority uptake for specific practice changes, and those strategies will transfer across at least some other practice changes.","rationale":"Cardiology's Get With The Guidelines and similar programmes showed that structured implementation measurably improves guideline adherence; oncology lacks equivalent evidence about what works.","test":"Fund five cluster-randomised implementation trials on current practice changes; report effect sizes and cost per additional patient receiving guideline-concordant care.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":3},{"id":"idea-tr1-immunotherapy-stop-trials","kind":"idea","name":"Randomised trials of stopping immunotherapy after one year versus continuing","aka":[],"tldr":"Immunotherapy is often given for two years or until it stops working, but responses can last long after stopping. Trials that randomly assign responders to stop or continue would show whether the extra year is needed.","summary":"Non-inferiority trials randomising patients with response or stable disease after 12 months of PD-1/PD-L1 therapy to discontinuation with surveillance and retreatment at progression versus continuation to 24 months or beyond, with a 'treatment-free interval' and cumulative drug exposure as secondary endpoints. Several academic trials (e.g., in melanoma and NSCLC) are under way; the proposal is to make stop-versus-continue a standard post-approval requirement for durable-response agents.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Trial design, endpoints and cost): Davis et al., Availability of evidence of benefits on survival and quality of life of cancer drugs approved by EMA 2009-13 (BMJ 2017)","url":"https://doi.org/10.1136/bmj.j4530"}],"tags":[],"related":[],"cancers":["melanoma","nsclc"],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":["pd1","pdl1"],"drugs":["pembrolizumab","nivolumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["checkmate-227","checkmate-915","fianlimab-phase3-melanoma","keynote-042","relativity-098"],"people":[],"bottlenecks":["b-trial-design","b-drug-pricing","b-toxicity-qol"],"keyPapers":["paper-davis-bmj","paper-topalian-anti-pd1-nejm-2012","paper-keynote-024-nejm-2016","paper-keynote-010-lancet-2016"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Stopping at 12 months in responders is non-inferior for OS with substantially lower cumulative toxicity and cost, and retreatment at progression recovers response in a meaningful fraction.","rationale":"Long-term follow-up of early checkpoint trials shows durable responses persisting for years after treatment ended; pharmacology suggests receptor occupancy persists for months.","test":"Pool the ongoing academic stop trials in a prospective meta-analysis with a pre-agreed non-inferiority margin; require sponsors of new checkpoint approvals to contribute to a duration trial.","maturity":"being-tested-at-scale","actor":"research","cost":"medium","horizonYears":4},{"id":"idea-tr2-biomarker-negative-arms","kind":"idea","name":"Randomised trials to test whether biomarker-negative patients really do not benefit","aka":[],"tldr":"Patients are denied a drug when a test says they will not benefit, but that restriction is usually inferred from enrichment trials rather than tested. For high-stakes markers with weak evidence in the negative group, such as PD-L1 and HER2 0, randomised trials in biomarker-negative patients should test the assumption itself.","summary":"Label restrictions based on biomarkers are often inferred from enrichment trials or subgroup analyses rather than from tests of the biomarker-negative population. For high-stakes markers with weak evidence in the negative group (PD-L1 in several tumours, HER2-ultralow and HER2 0, HRD-negative for PARP inhibitors), academic randomised trials in the biomarker-negative population with pragmatic endpoints would either open access to a denied group or firmly justify the restriction.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Biomarkers are not validated or standardised): Fernandez et al., Examination of low ERBB2 protein expression in breast cancer tissue (JAMA Oncology 2022)","url":"https://doi.org/10.1001/jamaoncol.2021.7239"}],"tags":[],"related":["her2-low","idea-tr2-marker-stratified-default"],"cancers":[],"sections":[],"technologies":[],"targets":["pdl1"],"drugs":["trastuzumab-deruxtecan"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["destiny-breast06"],"people":[],"bottlenecks":["b-biomarker-validation","b-immunotherapy-response"],"keyPapers":["paper-destiny-breast06-nejm-2024","paper-fernandez-jama-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"At least one of three trials in biomarker-negative populations will demonstrate clinically meaningful benefit, changing a label or guideline within five years.","rationale":"T-DXd showed activity in HER2-ultralow and possibly HER2 0 populations excluded by the original biomarker, and PD-1 blockade benefits some PD-L1-negative patients in several tumour types.","test":"Fund three cooperative-group randomised trials in biomarker-negative populations with overall survival or quality-of-life primary endpoints.","maturity":"early-clinical","actor":"research","cost":"large","horizonYears":5},{"id":"idea-acc-rapid-diagnostic-centres-vague-symptoms","kind":"idea","name":"Rapid diagnostic centres for people with vague but worrying symptoms","aka":[],"tldr":"Weight loss, fatigue and unexplained pain do not point to one organ, so patients bounce between specialists. A single clinic that investigates such symptoms quickly finds cancers that would otherwise be found late.","summary":"Site-specific urgent referral pathways miss patients with non-specific symptoms, who make up a large share of late-stage and emergency diagnoses. Denmark pioneered and England has scaled non-specific symptom pathways and rapid diagnostic centres, which investigate within days and detect cancer in a meaningful fraction of referrals, often in less common cancers. The proposal is to make such centres a standard component of cancer diagnostic systems.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Fragmented care and guideline gaps): Hanna et al., Mortality due to cancer treatment delay: systematic review and meta-analysis (BMJ 2020)","url":"https://doi.org/10.1136/bmj.m4087"}],"tags":[],"related":[],"cancers":["pancreatic","gastric","multiple-myeloma"],"sections":["diagnostics"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-care-fragmentation","b-early-detection"],"keyPapers":["paper-hanna-bmj"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Regions with rapid diagnostic centres will reduce the proportion of cancers first diagnosed through emergency presentation by at least 20% and shorten the diagnostic interval for cancers with non-specific presentations.","rationale":"Emergency-route diagnosis carries markedly worse survival; a dedicated pathway for the patients most likely to end up there is the obvious counter.","test":"Compare emergency-presentation rates, stage distribution, and diagnostic intervals in regions before and after centres open against regions without them.","maturity":"being-tested-at-scale","actor":"clinic","cost":"medium","horizonYears":3},{"id":"idea-pdac-ras-inhibitor-combinations-and-sequencing","kind":"idea","name":"RAS inhibitor combinations and sequence: pan-RAS plus G12D-selective, plus chemotherapy, and what to give after progression","aka":[],"tldr":"The first drug against the KRAS protein nearly doubled survival in pancreatic cancer in 2026, but on its own it holds the disease for months, not years. Trials are now testing it in combination with a second RAS drug and with chemotherapy, and earlier in the disease; the open questions are which combination, in which order, and what works when the tumour escapes.","summary":"RASolute 302 (500 patients, second line) gave daraxonrasib a median survival of 13.2 against 6.7 months (hazard ratio 0.40) and approval in August 2026. The chemistry (Holderfield 2024) inhibits active mutant and wild-type RAS together, so the drug is agnostic to allele but carries wild-type-RAS toxicity (rash, stomatitis); the G12D-selective zoldonrasib spares normal tissue and, combined with daraxonrasib, is meant to close the wild-type and secondary-mutation escape routes (the pairing record g12d-plus-pan-ras). The registry now holds RASolute 303 (first line, alone or with gemcitabine and nab-paclitaxel, 900 estimated, primary completion June 2028), RASolute 309 (zoldonrasib plus daraxonrasib against chemotherapy in G12D disease, 400, March 2029), RASolute 304 (adjuvant, 500, May 2029), Incyte's DAWN-303 (G12D inhibitor with chemotherapy, 588, September 2028) and a G12D competitor trial (GFH375). What none of these answers is sequence: whether a patient who progresses on a RAS inhibitor benefits from a different one, whether chemotherapy after RAS inhibition retains its activity, and whether ctDNA clearance can be used to stop or switch early. Resistance through secondary RAS mutations, receptor tyrosine kinase bypass and adaptive feedback is already described in the roadmap's open problems.","asOf":"2026-09-24","links":[{"label":"ClinicalTrials.gov NCT07491445","url":"https://clinicaltrials.gov/study/NCT07491445"},{"label":"ClinicalTrials.gov NCT07805954","url":"https://clinicaltrials.gov/study/NCT07805954"},{"label":"ClinicalTrials.gov NCT07252232","url":"https://clinicaltrials.gov/study/NCT07252232"},{"label":"ClinicalTrials.gov NCT07522073","url":"https://clinicaltrials.gov/study/NCT07522073"},{"label":"Holderfield et al.: concurrent inhibition of oncogenic and wild-type RAS-GTP (Nature 2024)","url":"https://europepmc.org/article/MED/38589574"}],"tags":["pancreatic-evidence"],"related":["g12d-plus-pan-ras","kras-roadmap","idea-ras-inhibitor-neoadjuvant-pdac"],"cancers":["pancreatic","metastatic-pdac","resectable-pdac"],"sections":[],"technologies":["kras-inhibitors","mrd-testing"],"targets":["kras"],"drugs":["daraxonrasib","zoldonrasib","elironrasib","mrtx1133","gemcitabine-nab-paclitaxel","folfirinox"],"companies":["revolution-medicines","incyte"],"institutions":[],"pathways":["ras-mapk"],"terms":["kras-mutation-subtypes","ctdna"],"trials":["rasolute-302","nct07491445","nct07805954","nct07252232","nct07522073","nct07262567"],"people":[],"bottlenecks":["b-resistance","b-combination-space","b-toxicity-qol"],"keyPapers":["paper-daraxonrasib-pancreatic-n-engl-j-med-2026","paper-holderfield-ras-on-multi-selective-inhibitor-nature-2024","paper-codebreak-100-sotorasib-kras-g12c-pancreatic-nejm-2023"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Combining a G12D-selective inhibitor with a pan-RAS(ON) inhibitor, or a RAS inhibitor with chemotherapy, extends first-line progression-free survival beyond either alone with acceptable added toxicity; and a pre-specified sequencing study shows a second RAS-directed line has activity after progression on the first.","rationale":"Single-agent survival gains are large but not durable; the escape routes are known and each has a drug; the trials are enrolling, and the sequencing question can be answered from their post-progression data if it is collected.","test":"RASolute 303, 309 and 304 and DAWN-303 readouts (2028 to 2029) with mandatory post-progression treatment capture and ctDNA sampling; a randomised sequencing sub-study (switch to a second RAS inhibitor versus chemotherapy at progression).","maturity":"being-tested-at-scale","actor":"industry","cost":"large","horizonYears":4},{"id":"idea-ras-inhibitor-neoadjuvant-pdac","kind":"idea","name":"RAS(ON) inhibitors to convert unresectable pancreatic cancer to resectable","aka":[],"tldr":"If daraxonrasib shrinks metastatic tumours this well, use it before surgery to make more locally advanced tumours operable.","summary":"The proposal is to give the RAS(ON) inhibitor daraxonrasib, with or without chemotherapy, before surgery for borderline resectable and locally advanced pancreatic ductal adenocarcinoma, to see whether it raises the R0 resection rate compared with mFOLFIRINOX. Surgery remains the only route to cure, yet only a minority of patients present with resectable disease. The rationale is the deep and rapid responses seen with daraxonrasib and zoldonrasib, oral dosing, ctDNA clearance as an early surrogate, and the fact that RASolute 303 and 304 already move the drug earlier. The test would be a randomised phase 2 with R0 resection as the primary endpoint. At an early clinical stage, it addresses the bottleneck of the undruggable drivers.","asOf":"2026-09-06","links":[{"label":"ClinicalTrials.gov NCT06625320: RASolute 302","url":"https://clinicaltrials.gov/study/NCT06625320"}],"tags":[],"related":[],"cancers":["pancreatic"],"sections":[],"technologies":["kras-inhibitors","mrd-testing"],"targets":["kras"],"drugs":["daraxonrasib","zoldonrasib","folfirinox"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["rasolute-302"],"people":[],"bottlenecks":[],"keyPapers":["paper-nct05379985-n-engl-j-med-2026","paper-daraxonrasib-pancreatic-n-engl-j-med-2026","paper-daraxonrasib-pancreatic-cureus-2026"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Neoadjuvant daraxonrasib (± chemotherapy) increases R0 resection rate and 2-year DFS in borderline/locally advanced PDAC compared with mFOLFIRINOX.","rationale":"Deep, rapid responses; oral dosing; ctDNA as an early surrogate; RASolute 303/304 already move the drug earlier.","test":"Randomised phase 2 with R0 resection as primary and DFS/OS secondary; pathologic response and ctDNA clearance as biomarkers.","maturity":"early-clinical"},{"id":"idea-bio1-antigen-mapping-at-progression","kind":"idea","name":"Re-map the tumour's surface proteins before choosing the next antibody drug","aka":[],"tldr":"Antibody drugs need their target to still be present. After one fails, checking which surface markers remain would guide the choice of the next one instead of guessing.","summary":"Antigen loss and downregulation are documented mechanisms of ADC, bispecific and CAR-T failure. A standardised multiplex panel measuring the main clinical antigens (HER2, TROP2, HER3, CEACAM5, B7-H3, Nectin-4, FOLR1 and others) on a progression biopsy, or by immuno-PET where available, would let clinicians select the next agent by present antigen rather than by tumour type convention.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Acquired resistance to every therapy): Soria et al., Osimertinib in untreated EGFR-mutated NSCLC (FLAURA, NEJM 2018)","url":"https://doi.org/10.1056/NEJMoa1713137"}],"tags":[],"related":["idea-payload-switching"],"cancers":[],"sections":[],"technologies":["adc","histopathology-ihc","immuno-pet","single-cell-spatial"],"targets":["her2","trop2","her3","ceacam5","b7h3","folr1"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-resistance","b-tumor-heterogeneity"],"keyPapers":["paper-slamon-her2-breast-ovarian-science-1989","paper-yarden-sliwkowski-erbb-network-nrmcb-2001"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Antigen-guided selection of the next antibody-based agent after progression yields a higher response rate than conventional selection, and antigen loss explains a substantial fraction of failures on the prior agent.","rationale":"Antigen expression is dynamic under treatment pressure and archival tissue is a poor guide; the panel technology is routine immunohistochemistry or multiplex imaging, so this is a logistics rather than discovery problem.","test":"Prospective cohort of 200 patients progressing on an ADC: run the panel, record whether the recommendation differs from the clinician's plan, and compare outcomes where it was followed.","maturity":"speculative","actor":"clinic","cost":"medium","horizonYears":4},{"id":"idea-bio1-rebiopsy-before-switch","kind":"idea","name":"Re-test the metastasis, not the old primary, before every change of treatment","aka":[],"tldr":"Treatment is often chosen from a biopsy taken years earlier from the original tumour. The spread disease may now look different. Test it again before switching drugs.","summary":"Receptor and biomarker discordance between primary and metastasis is well documented (oestrogen receptor, HER2, PD-L1, and actionable alterations). Yet most line changes rely on archival tissue. The proposal is a payer-backed policy that a contemporaneous biopsy or validated liquid biopsy is offered before each line change in metastatic disease, with a registry to quantify how often the result changes therapy.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Tumour heterogeneity and clonal evolution): Gerlinger et al., Intratumor heterogeneity and branched evolution (NEJM 2012)","url":"https://doi.org/10.1056/NEJMoa1113205"}],"tags":[],"related":[],"cancers":["breast-hr-positive","breast-her2-positive","nsclc"],"sections":[],"technologies":["liquid-biopsy","histopathology-ihc","cgp"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["her2-low","ihc"],"trials":[],"people":[],"bottlenecks":["b-tumor-heterogeneity","b-resistance"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Contemporaneous re-testing changes the selected therapy in at least 15 percent of line changes and is cost-neutral or cost-saving through avoided ineffective treatment.","rationale":"Discordance rates of 10 to 30 percent for key biomarkers are consistently reported; the rate of unnecessary or missed targeted therapy is a direct cost to payers.","test":"Coverage-with-evidence pilot in one health system: fund re-testing for 1,000 line changes, record decision changes and downstream costs over 18 months.","maturity":"early-clinical","actor":"payer","cost":"medium","horizonYears":2},{"id":"idea-bio2-ai-sarcopenia-from-ct","kind":"idea","name":"Read muscle loss automatically from scans patients already have","aka":[],"tldr":"Every staging scan contains a precise measure of muscle mass that nobody looks at. Software could report it automatically and flag patients heading for wasting.","summary":"Automated segmentation of skeletal muscle at the third lumbar vertebra is accurate and fast, and low muscle mass predicts chemotherapy toxicity, surgical complications and survival across tumour types. The measurement is free because the scans already exist; the missing pieces are automated reporting into the record and a defined action when the value is low.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Cachexia, toxicity and the limits of the patient): Fearon et al., Definition and classification of cancer cachexia (Lancet Oncology 2011)","url":"https://doi.org/10.1016/S1470-2045(10)70218-7"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["radiology-ai-screening","ct","geriatric-assessment","exercise-oncology"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-cachexia-supportive","b-ai-validation","b-toxicity-qol"],"keyPapers":["paper-fearon-lancet-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Automated muscle metrics reported with every staging scan identify high-risk patients earlier than weight loss criteria, and triggering a supportive care pathway on that flag improves treatment completion rates.","rationale":"Opportunistic imaging biomarkers have already been adopted for bone density and coronary calcium from routine scans. Cachexia is currently diagnosed late, by weight loss that has already occurred, when reversal is hardest.","test":"Deploy automated segmentation in one centre and randomise by clinic to flag-triggered referral versus usual care; endpoints are treatment completion, dose intensity and hospital admissions.","maturity":"preclinical-evidence","actor":"data","cost":"small","horizonYears":3},{"id":"idea-bio2-csf-ctdna-monitoring","kind":"idea","name":"Read the spinal fluid to track brain tumours without opening the skull","aka":[],"tldr":"Fluid taken from the lower back contains DNA from brain tumours. Testing it can diagnose, monitor and detect resistance without brain surgery.","summary":"Cerebrospinal fluid ctDNA outperforms plasma for central nervous system tumours and detects leptomeningeal disease earlier than cytology or MRI in several studies, including paediatric brain tumours and lymphoma. Standardisation, assay validation and demonstrating that acting on the result improves outcomes are the missing pieces.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The brain: barrier and sanctuary): Stupp et al., Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma (NEJM 2005)","url":"https://doi.org/10.1056/NEJMoa043330"}],"tags":[],"related":[],"cancers":["glioblastoma","breast-her2-positive","dlbcl"],"sections":[],"technologies":["liquid-biopsy","mrd-testing","mri"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["ctdna","mrd","h3k27m"],"trials":[],"people":[],"bottlenecks":["b-brain-delivery","b-dormancy-mrd","b-biomarker-validation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Serial cerebrospinal fluid ctDNA detects central nervous system progression a median of two months before MRI and identifies resistance mutations that change treatment in at least a quarter of patients.","rationale":"Cerebrospinal fluid is a low-background compartment adjacent to the tumour, giving far higher tumour fraction than plasma. Lumbar puncture is routine, repeatable and cheap compared with any brain imaging or biopsy.","test":"A prospective monitoring cohort in glioma and in HER2-positive or ALK-positive brain metastasis with paired MRI, reporting lead time and the proportion of patients whose management changes.","maturity":"early-clinical","actor":"clinic","cost":"small","horizonYears":4},{"id":"idea-data-guideline-concordance-dashboards","kind":"idea","name":"Real-time guideline-concordance feedback for every cancer centre","aka":[],"tldr":"Show each hospital, every month, how often its patients received the recommended treatment, compared with peers, so gaps are seen and closed.","summary":"Audit and feedback is one of the best-evidenced ways to change clinical practice, but oncology audits are infrequent and slow. Using structured data (mCODE) and computable guidelines, concordance for key decisions (biomarker testing before first-line therapy, adjuvant therapy in eligible patients, guideline-recommended regimens) can be computed monthly per centre and fed back with peer comparison. Precedents include ASCO's QOPI and the Dutch cancer audits (DICA).","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Knowledge reaches practice too slowly): Morris, Wooding & Grant, The answer is 17 years, what is the question (JRSM 2011)","url":"https://doi.org/10.1258/jrsm.2011.110180"}],"tags":[],"related":["idea-data-computable-living-guidelines"],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["asco"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-knowledge-diffusion","b-care-fragmentation"],"keyPapers":["paper-morris-j-r-soc-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Monthly automated feedback will close the gap between actual and recommended care for measured decisions by at least half within two years, particularly for biomarker testing rates.","rationale":"Cochrane reviews find audit and feedback improves adherence by a median of several percentage points, more when frequent and with peer comparison; automation removes the cost barrier to frequency.","test":"Randomise 40 centres to monthly automated feedback or annual audit; measure biomarker testing and guideline-concordant first-line therapy rates at 18 months.","maturity":"early-clinical","actor":"clinic","cost":"medium","horizonYears":2},{"id":"idea-moon-image-guided-surgery-everywhere","kind":"idea","name":"Real-time margin assessment and image-guided surgery as the global standard","aka":[],"tldr":"Surgeons often cannot see where a tumour ends. Fluorescent dyes and AI-read imaging in the operating theatre can show them, cutting repeat operations. Make this routine everywhere.","summary":"Positive margins lead to re-operation or recurrence in breast, head and neck, prostate and gastrointestinal surgery. Tumour-targeted fluorescent agents (pegulicianine approved for breast lumpectomy, PSMA- and folate-targeted agents), intraoperative mass spectrometry and rapid AI histology can assess margins during surgery. The proposal is a programme to standardise and validate these tools across common operations, integrate them into low-cost surgical imaging platforms suitable for district hospitals, and make margin status with intraoperative assessment a quality indicator.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Surgery and radiotherapy cure most, get least): Sullivan et al., Global cancer surgery (Lancet Oncology Commission 2015)","url":"https://doi.org/10.1016/S1470-2045(15)00223-5"}],"tags":[],"related":[],"cancers":["head-and-neck","breast-hr-positive","prostate"],"sections":[],"technologies":["fluorescence-guided-surgery","optical-imaging","digital-pathology-ai"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-surgery-radiation-innovation","b-global-access"],"keyPapers":["paper-sullivan-lancet-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Routine intraoperative margin assessment halves positive margin rates and re-operations in breast and head and neck surgery, and low-cost versions perform equivalently in resource-limited hospitals.","rationale":"Surgery remains the most curative treatment for most solid tumours and its main technical failure is invisible margins; the imaging agents and readers now exist.","test":"Randomised trials of image-guided versus standard surgery in breast and oral cancer with positive margin rate as primary endpoint, plus a validation of low-cost imaging systems in two middle-income countries.","maturity":"early-clinical","actor":"engineering","cost":"large","horizonYears":6},{"id":"idea-data-real-world-dose-intensity","kind":"idea","name":"Real-world dose intensity and toxicity monitoring to revise labelled doses","aka":[],"tldr":"Track how much of each cancer drug patients actually receive and how often they need to reduce it, and use that to change the official dose when the label is too high.","summary":"Oncology drugs are often labelled at doses most patients cannot tolerate; dose reductions in practice are common but invisible to regulators. Project Optimus addresses dose selection before approval; nothing systematic addresses it after. The proposal uses structured prescribing data to publish real-world dose intensity, reduction rates and toxicity per drug annually, with a regulatory pathway to update labels when the real-world modal dose differs from the label.","asOf":"2026-09-08","links":[{"label":"FDA Project Optimus","url":"https://www.fda.gov/about-fda/oncology-center-excellence/project-optimus"}],"tags":[],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["real-world-evidence"],"trials":[],"people":[],"bottlenecks":["b-real-world-evidence","b-dose-optimisation","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Systematic real-world dose monitoring will identify at least ten approved oncology drugs where more than half of patients are dose-reduced, and label revision or randomised dose-optimisation trials will follow for a majority of them.","rationale":"Post-marketing dose changes (for example for several kinase inhibitors and ADCs) have happened only after years of ad hoc reports; structured data would surface the problem in months.","test":"Compute dose-intensity metrics for the 30 most-used oral targeted agents in one national prescribing dataset; publish; track subsequent label or guideline changes over three years.","maturity":"early-clinical","actor":"regulator","cost":"small","horizonYears":2},{"id":"idea-data-outcome-based-price-reassessment","kind":"idea","name":"Reassess cancer drug prices at three years using real-world outcomes","aka":[],"tldr":"Set the price of a new cancer drug provisionally, then adjust it up or down after three years depending on how well patients actually did.","summary":"Prices are set at approval on trial data and rarely revisited. Outcome-based agreements exist but are bespoke and opaque. The proposal is a standard pricing rule: initial price tied to trial evidence, mandatory structured outcome capture, and a scheduled reassessment at three years using pre-specified real-world survival and toxicity metrics, with published adjustment formulae. Italy's AIFA registries and Germany's AMNOG reassessments are partial precedents.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Weak real-world evidence and registries): Gyawali, Hey & Kesselheim, Assessment of the clinical benefit of cancer drugs receiving accelerated approval (JAMA Intern Med 2019)","url":"https://doi.org/10.1001/jamainternmed.2019.0462"}],"tags":[],"related":["idea-data-coverage-with-evidence-development"],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["real-world-evidence"],"trials":[],"people":[],"bottlenecks":["b-real-world-evidence","b-drug-pricing","b-incentive-misalignment"],"keyPapers":["paper-gyawali-jama-intern-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Scheduled reassessment will lower prices for drugs whose real-world benefit falls short of trial results and will make outcome capture near-complete because payment depends on it.","rationale":"Payment tied to data has been the only reliable driver of completeness (see SACT); tying price to outcome aligns the incentive to collect with the incentive to deliver value.","test":"Apply the rule to ten new indications in one national payer; report data completeness and the direction and size of price adjustments at reassessment.","maturity":"early-clinical","actor":"payer","cost":"medium","horizonYears":4},{"id":"idea-moon-reciprocal-tumour-agnostic-approvals","kind":"idea","name":"Reciprocal recognition of tumour-agnostic and rare-indication approvals across regulators","aka":[],"tldr":"When a trusted regulator approves a cancer drug for a rare genetic target, other countries should recognise that approval within months instead of repeating years of review.","summary":"Tumour-agnostic and biomarker-defined rare indications (NTRK fusions, MSI-high, RET, BRAF V600E) are approved at different times in different regions, and many countries never review them at all, leaving patients without access. Reliance pathways (Project Orbis, Access Consortium, WHO collaborative registration) show regulatory reliance works. The proposal is a formal reciprocal recognition agreement for defined categories, with automatic provisional authorisation in participating countries within 90 days of a reference approval, shared post-marketing obligations, and pricing negotiated in parallel.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Regulatory divergence between regions): FDA Oncology Center of Excellence, Project Orbis","url":"https://www.fda.gov/about-fda/oncology-center-excellence/project-orbis"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":["ntrk","ret","braf"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["tumour-agnostic","accelerated-approval"],"trials":[],"people":[],"bottlenecks":["b-regulatory-fragmentation","b-global-access"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Reciprocal recognition cuts the median gap between first and subsequent approvals for these indications from years to under six months and increases the number of countries with access severalfold.","rationale":"Duplicate review adds delay and cost without adding safety for indications with identical evidence; reliance is already accepted policy for vaccines and generics in many jurisdictions.","test":"Agreement among five regulators for tumour-agnostic indications; measure time to authorisation and access before and after.","maturity":"early-clinical","actor":"regulator","cost":"small","horizonYears":3},{"id":"idea-acc-diagnostic-interval-public-registry","kind":"idea","name":"Record and publish the symptom-to-diagnosis interval for every cancer, by hospital","aka":[],"tldr":"How long people wait between first noticing something wrong and being diagnosed is barely measured. Recording it routinely and publishing it by hospital would expose where the system loses time.","summary":"The diagnostic interval is the most patient-relevant delay in cancer care and the least measured. Adding first-presentation date and referral dates to cancer registry minimum datasets, and publishing intervals by route and hospital, would let systems see whether delays occur before referral (primary care), in diagnostics, or in specialist queues. Denmark and England collect parts of this; almost no one else does.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Fragmented care and guideline gaps): Hanna et al., Mortality due to cancer treatment delay: systematic review and meta-analysis (BMJ 2020)","url":"https://doi.org/10.1136/bmj.m4087"}],"tags":[],"related":["seer"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-care-fragmentation","b-early-detection","b-real-world-evidence"],"keyPapers":["paper-hanna-bmj"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Systems that measure and publish diagnostic intervals will reduce median intervals for the four commonest cancers by at least 15% within three years as bottlenecks become visible and are addressed.","rationale":"What is measured improves; the routes-to-diagnosis work in England showed that emergency presentations and long intervals predict shorter survival, motivating change once visible.","test":"Add the fields to a national registry, publish annually, and compare interval trends with a comparator country without measurement.","maturity":"speculative","actor":"data","cost":"small","horizonYears":2},{"id":"idea-tr2-preanalytics-in-report","kind":"idea","name":"Record how long tissue waited before fixation in every pathology report","aka":[],"tldr":"How a tissue sample is handled before it reaches the lab changes the results of biomarker tests. That handling time is almost never recorded, so nobody can tell a true negative from a spoiled sample.","summary":"Cold ischaemia time and fixation duration affect phosphoprotein, RNA and even some IHC markers (including HER2 and ER), yet pre-analytical variables are rarely recorded in structured form. Guidelines (ASCO/CAP for HER2) specify limits but compliance is unmeasured. Adding mandatory structured fields for time to fixation and fixation duration to pathology reporting standards and laboratory information systems would let biomarker results be interpreted, audited and used in research.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Biomarkers are not validated or standardised): Fernandez et al., Examination of low ERBB2 protein expression in breast cancer tissue (JAMA Oncology 2022)","url":"https://doi.org/10.1001/jamaoncol.2021.7239"}],"tags":[],"related":["idea-tr2-eqa-public-results"],"cancers":[],"sections":[],"technologies":["histopathology-ihc"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["ihc"],"trials":[],"people":[],"bottlenecks":["b-biomarker-validation"],"keyPapers":["paper-fernandez-jama-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Once recorded, pre-analytical time will explain a measurable share of the between-hospital variation in biomarker positivity rates, and hospitals with out-of-range times will improve within a year of feedback.","rationale":"Clinical chemistry rejects samples with documented pre-analytical faults; anatomic pathology has no equivalent because the data are not captured.","test":"Implement the fields in five hospitals; correlate recorded times with HER2 and ER positivity rates and with repeat-test rates.","maturity":"speculative","actor":"clinic","cost":"small","horizonYears":2},{"id":"idea-tr2-off-label-outcome-registry","kind":"idea","name":"Record what happens when doctors use cancer drugs off-label","aka":[],"tldr":"Cancer drugs are often prescribed outside their approved use based on hope or small studies. Capturing outcomes of these uses would reveal which ones fail so they can be stopped.","summary":"Off-label use is common in oncology, particularly for targeted agents matched to molecular alterations in other cancers. Structured outcome capture at the point of off-label prescribing (indication, rationale, response, duration, toxicity) through a simple registry, as the Dutch DRUP trial and the US TAPUR study do within trial frameworks, but extended to routine practice, would document failures that are otherwise invisible.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Failures are hidden): Anderson et al., Compliance with results reporting at ClinicalTrials.gov (NEJM 2015)","url":"https://doi.org/10.1056/NEJMsa1409364"}],"tags":[],"related":["idea-tr2-payer-combo-cwe"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["tumour-agnostic","real-world-evidence"],"trials":[],"people":[],"bottlenecks":["b-negative-results","b-real-world-evidence"],"keyPapers":["paper-anderson-n-engl-j-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A national off-label registry will identify at least five drug-alteration-cancer combinations with response rates below 10% in over 50 patients within three years, leading to guideline statements against their use.","rationale":"DRUP and TAPUR have both closed cohorts for futility, generating negative evidence that changed practice. Most off-label use happens outside such studies and is never counted.","test":"Mandate registry entry as a condition of off-label reimbursement in one health system; report cohort response rates annually.","maturity":"early-clinical","actor":"clinic","cost":"medium","horizonYears":3},{"id":"idea-moon-recorded-consultations","kind":"idea","name":"Recorded, AI-summarised consultations given to patients by default","aka":[],"tldr":"Every cancer consultation is recorded with consent and the patient receives the audio plus a checked written summary of what was said and decided.","summary":"Patients recall a fraction of what is said in oncology consultations and recall worsens with anxiety and bad news. Studies of consultation recordings show improved recall and satisfaction with no harm to clinicians. Ambient AI scribes now produce draft summaries from audio. The proposal is that recording and a patient-facing summary (decisions, next steps, questions asked, plain glossary) become the default, with the clinician approving the summary and the patient able to share it with family.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Patients lack understanding, navigation and agency): Basch et al., Overall survival results of a trial assessing patient-reported outcomes for symptom monitoring during routine cancer treatment (JAMA 2017)","url":"https://doi.org/10.1001/jama.2017.7156"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-patient-voice","b-knowledge-diffusion"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Default recording and summaries improve recall of key facts at one week by at least 25% and reduce repeat calls, with no increase in complaints or litigation.","rationale":"Recall failure is a format problem; audio and summary are cheap and already supported by scribe technology being adopted for clinician documentation.","test":"Randomised trial in two clinics: recording plus summary versus usual care; primary outcome recall of diagnosis, prognosis and plan at one week; secondary decisional conflict and satisfaction.","maturity":"early-clinical","actor":"engineering","cost":"small","horizonYears":1},{"id":"idea-reg-legacy-radium-recovery-ac225","kind":"idea","name":"Recover legacy radium-226 sources worldwide as the feedstock for actinium-225","aka":[],"tldr":"Thousands of old radium sources sit in hospital and industrial storage. They are exactly the raw material needed to make actinium-225, the scarcest cancer isotope.","summary":"Actinium-225 supply from thorium-229 generators (the legacy US and Russian stockpiles) is limited to tens of curies a year, far short of projected demand for alpha radioligand therapy. Accelerator routes (radium-226 irradiated in cyclotrons, linacs or via spallation at TRIUMF) scale with radium feedstock. Radium-226 exists in large quantities in disused brachytherapy sources, industrial gauges and uranium mill tailings, currently classed as waste and expensive to store. The proposal is a coordinated recovery, purification and target-fabrication programme run with the IAEA and national nuclear agencies, offering source holders free disposal in exchange for the material.","asOf":"2026-09-08","links":[{"label":"IAEA on actinium-225 supply","url":"https://www.iaea.org/newscenter/news/actinium-225-production-and-supply"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["targeted-alpha-therapy","radioligand-therapy"],"targets":[],"drugs":["ac225-psma","ryz101"],"companies":["terrapower-isotopes","orano-med"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-manufacturing-cell-therapy"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Recovered radium-226 sufficient to supply multiple accelerator producers can be secured within five years at a cost per curie of actinium-225 below the thorium-generator route, lifting global actinium-225 output by an order of magnitude.","rationale":"Radium disposal is already a cost that source holders would pay to avoid, and purification chemistry is established. The binding constraint on the accelerator route is licensed feedstock, not physics.","test":"Inventory recoverable radium-226 in ten countries, run a pilot recovery of 50 grams with one accelerator producer, and price the resulting actinium-225 against current generator supply.","maturity":"early-clinical","actor":"policy","cost":"medium","horizonYears":4},{"id":"idea-data-ai-red-team-programme","kind":"idea","name":"Red-team programmes that attack cancer AI before patients do","aka":[],"tldr":"Pay independent experts to try to break cancer AI tools with unusual images, rare cases, bad scans and data shifts, and publish what breaks them.","summary":"Robustness of medical AI to artefacts, rare presentations, adversarial inputs and distribution shift is poorly characterised. The proposal funds standing red teams (imaging physicists, pathologists, security researchers) that stress-test cleared and pre-clearance cancer AI with curated adversarial and edge-case corpora, publish failure modes in a common taxonomy, and feed results to the registry and developers, as is done for cybersecurity and increasingly for general-purpose AI.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (AI that is built but not validated or deployed): Wu et al., How medical AI devices are evaluated: limitations and recommendations from an analysis of FDA approvals (Nature Medicine 2021)","url":"https://doi.org/10.1038/s41591-021-01312-x"}],"tags":[],"related":["idea-data-sequestered-prospective-benchmarks"],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-ai-validation"],"keyPapers":["paper-wu-nat-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Red-teaming will uncover clinically relevant failure modes in most tested models that were not disclosed in their validation, and disclosure will lead to fixes or labelling changes.","rationale":"Every mature safety-critical field uses adversarial testing; medical AI relies on developers' own validation, which is structurally blind to what the developers did not think of.","test":"Red-team ten cancer AI tools over one year; publish findings; track developer responses and label changes within a further year.","maturity":"speculative","actor":"research","cost":"small","horizonYears":1},{"id":"idea-gbc-prophylactic-cholecystectomy-targeted-and-evaluated","kind":"idea","name":"Redesign Chile's prophylactic cholecystectomy programme around risk, and evaluate it properly","aka":[],"tldr":"Chile has paid for preventive gallbladder removal in 35 to 49 year olds with stones since 2006 without a design that can show whether it prevents cancer deaths. Targeting the operation by region, ancestry and risk score, with an evaluation built in, would answer the question the world's only such programme has left open for twenty years.","summary":"The GES programme has issued 284,139 notifications since 2006. Standardised gallbladder cancer mortality has fallen, but was falling before the programme, and the 2019 analysis found the targeted age group's mortality decline doubled (4 to 8 percent per period) without a national break in trend. High-incidence areas do not receive proportionally more operations. Genetic work shows Mapuche ancestry raises risk independently of stones and body mass index, and exome studies show Chilean tumours carry the lowest mutation burden of five countries studied. A risk-based redesign (region, ancestry-informed score, sex, typhoid history) with a stepped-wedge or regression-discontinuity evaluation would make the programme both more efficient and, for the first time, measurable.","asOf":"2026-09-24","links":[{"label":"Samaniego et al.: is it time to modify the GES programme (Rev Med Chile 2024)","url":"https://europepmc.org/article/MED/40052976"},{"label":"Zollner et al.: Mapuche ancestry and gallbladder cancer risk, instrumental variable analysis (Cancers 2023)","url":"https://europepmc.org/article/MED/37627062"}],"tags":["gallbladder-evidence"],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["falp-chile","nci"],"pathways":[],"terms":["prophylactic-cholecystectomy","screening"],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption","b-real-world-evidence"],"keyPapers":["paper-samaniego-chile-ges-programme-evaluation-rev-med-chile-2024","paper-mardones-frenz-chile-ges-mortality-rev-med-chile-2019","paper-cid-chile-programme-gallbladder-cancer-mortality-am-j-epidemiol-2024","paper-garate-calderon-gallbladder-cancer-worldwide-exome-ebiomedicine-2026"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Reallocating GES cholecystectomy capacity to a validated risk score rather than an age band will reduce gallbladder cancer mortality per operation performed by at least 30 percent, and a built-in stepped-wedge rollout will detect that effect within ten years.","rationale":"The programme's marginal benefit is highest where incidence and individual risk are highest; current allocation by age alone ignores both.","test":"Stepped-wedge rollout of the risk-based allocation across health service regions, with gallbladder cancer mortality and incidence from national statistics as primary outcomes and operations per prevented death as the efficiency measure.","maturity":"being-tested-at-scale","actor":"policy","cost":"large","horizonYears":10},{"id":"idea-tr1-response-adapted-dose-reduction","kind":"idea","name":"Reduce the dose once the cancer responds: response-adapted de-escalation trials","aka":[],"tldr":"The dose needed to shrink a tumour may be higher than the dose needed to keep it from growing back. Trials that lower the dose once a response is achieved could reduce long-term side effects without losing control.","summary":"Randomised trials in which patients achieving a defined response (radiographic, molecular or biochemical) after induction are allocated to continue full dose or step down to a maintenance dose (e.g., 50 percent), with resumption of full dose on progression. Precedents include dose reduction of dasatinib and other TKIs in chronic-phase CML after deep response, and maintenance de-escalation strategies in myeloma; the proposal extends the approach to solid-tumour targeted agents and ADCs where chronic toxicity accumulates.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Wrong doses): FDA Oncology Center of Excellence, Project Optimus","url":"https://www.fda.gov/about-fda/oncology-center-excellence/project-optimus"}],"tags":[],"related":[],"cancers":["cll","multiple-myeloma","breast-her2-positive"],"sections":[],"technologies":["kinase-inhibitors","adc"],"targets":[],"drugs":["imatinib","trastuzumab-deruxtecan"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-dose-optimisation","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Response-adapted de-escalation will be non-inferior for PFS with a substantial reduction in cumulative toxicity and cost, and progression on the reduced dose will be salvageable by re-escalation in most cases.","rationale":"Tumour burden and the number of cells that must be suppressed fall after response; pharmacological suppression of residual disease may require less exposure than debulking, as CML dose-reduction studies suggest.","test":"Randomised phase 3 non-inferiority trials in two settings (an oral targeted agent in a solid tumour and an ADC) with PFS primary and cumulative toxicity, QoL and cost as secondaries.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":4},{"id":"idea-bio2-mrd-reference-standards","kind":"idea","name":"Reference materials and open proficiency testing for residual disease tests","aka":[],"tldr":"Different companies' leftover-cancer blood tests disagree, and there is no shared yardstick. Public reference samples would let anyone check which test actually works.","summary":"Tumour-informed and tumour-naive ctDNA assays report different sensitivities at different variant allele fractions, and cross-assay comparisons are almost entirely vendor-run. A public reference material programme (synthetic and patient-derived contrived plasma at defined fractions, blinded rounds, published per-assay results) would do for MRD what proficiency schemes did for HER2 immunohistochemistry.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Dormant cells and minimal residual disease): Tie et al., ctDNA analysis guiding adjuvant therapy in stage II colon cancer (NEJM 2022)","url":"https://doi.org/10.1056/NEJMoa2200075"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["mrd-testing","liquid-biopsy","ngs-mrd-clonoseq"],"targets":[],"drugs":[],"companies":["natera","guardant-health","foresight-diagnostics","adaptive-biotechnologies"],"institutions":[],"pathways":[],"terms":["vaf","mrd"],"trials":[],"people":[],"bottlenecks":["b-dormancy-mrd","b-biomarker-validation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Blinded proficiency testing reveals at least a threefold spread in limit of detection between commercial MRD assays at 0.01% variant allele fraction, and publishing results narrows that spread within two rounds.","rationale":"Every biomarker that decides treatment eventually needs external quality assessment; HER2 and PD-L1 scoring both improved measurably once schemes existed. MRD is about to gate adjuvant therapy decisions, so the cost of unquantified variability is now clinical.","test":"A metrology institute or reference laboratory network produces contrived plasma panels and runs one blinded round with five commercial and three academic assays, publishing all results with assay names attached.","maturity":"speculative","actor":"regulator","cost":"small","horizonYears":3},{"id":"idea-gbc-reflex-her2-testing-advanced-biliary","kind":"idea","name":"Reflex HER2 testing of every advanced gallbladder and extrahepatic biliary cancer","aka":[],"tldr":"Between one in eleven and one in five gallbladder cancers is HER2-positive and two HER2 drugs are now approved, but testing still happens only when someone asks. Making it automatic on every advanced biliary diagnosis, on resection tissue where it exists, would find the patients the trials were built for.","summary":"HER2 overexpression is about 20 percent in extrahepatic biliary cancers in the 2017 meta-analysis and 9.4 percent of gallbladder cancers by the HERIZON-BTC-01 definition in a 2026 resected series, which also found frequent heterogeneity involving under half of tumour cells, so small biopsies can miss it. Zanidatamab produced a 41.3 percent response rate in HER2-positive disease and trastuzumab deruxtecan has a tumour-agnostic HER2 3+ indication. Testing uptake in biliary cancer is not routinely audited. Reflex immunohistochemistry with in situ hybridisation for 2+ cases, ordered by pathology at diagnosis, is the model used for gastric and breast cancer.","asOf":"2026-09-24","links":[{"label":"Angerilli et al.: HER2 status and heterogeneity in 140 resected biliary cancers (Hum Pathol 2026)","url":"https://europepmc.org/article/MED/42595189"},{"label":"HERIZON-BTC-01 (Lancet Oncol 2023)","url":"https://europepmc.org/article/MED/37276871"}],"tags":["gallbladder-evidence"],"related":[],"cancers":["gallbladder","extrahepatic-cholangiocarcinoma"],"sections":[],"technologies":[],"targets":["her2"],"drugs":["zanidatamab","trastuzumab-deruxtecan"],"companies":[],"institutions":[],"pathways":[],"terms":["her2-positive","ihc","fish"],"trials":["herizon-btc-01","herizon-btc-302","destiny-pantumor02"],"people":[],"bottlenecks":["b-biomarker-validation","b-knowledge-diffusion"],"keyPapers":["paper-galdy-her2-biliary-tract-meta-analysis-cancer-metastasis-rev-2017","paper-angerilli-her2-ihc-cish-biliary-hum-pathol-2026","paper-harding-lancet-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Pathology-initiated reflex HER2 testing at diagnosis of advanced gallbladder or extrahepatic biliary cancer will raise the tested fraction to above 90 percent and double the number of patients receiving HER2-directed therapy within two years.","rationale":"The drugs exist and are approved; the bottleneck is a test that is cheap, standardised and already run in every pathology laboratory for other cancers.","test":"Before-and-after audit across a hepatobiliary network: proportion tested, turnaround time, HER2-positive rate, proportion of positives treated, with a heterogeneity sub-study comparing biopsy and resection specimens.","maturity":"early-clinical","actor":"clinic","cost":"small","horizonYears":2},{"id":"idea-tnbc-her2-ultralow-testing-uptake","kind":"idea","name":"Reflex re-scoring of HER2 0 versus 1+ with digital assistance so every eligible triple-negative patient reaches trastuzumab deruxtecan","aka":[],"tldr":"About a third of triple-negative tumours are HER2-low and so eligible for trastuzumab deruxtecan, but the difference between a HER2 score of 0 and 1+ is the one pathologists agree on least, and most triple-negative tumours were scored before the label mattered. Re-scoring archived slides with digital help when a patient relapses would find the eligible third.","summary":"Schettini's 3,689-patient study found HER2-low in 36.6 percent of triple-negative tumours, no biological difference between HER2-low and HER2 0 triple-negative disease, and suboptimal reproducibility of the HER2-low call among pathologists; DESTINY-Breast04 showed trastuzumab deruxtecan lengthens survival in HER2-low metastatic disease including the triple-negative cohort. The HER2 score was designed to find amplification, so the 0 versus 1+ distinction was never quality-assured, and the HER2-ultralow category (0 with faint staining in 10 percent or fewer cells) that DESTINY-Breast06 validated in hormone receptor-positive disease has no triple-negative evidence yet. Digital scoring algorithms for HER2 low expression are in validation.","asOf":"2026-09-24","links":[{"label":"Schettini et al.: clinical, pathological and PAM50 features of HER2-low breast cancer (NPJ Breast Cancer 2021)","url":"https://europepmc.org/article/MED/33397968"}],"tags":["tnbc-evidence"],"related":[],"cancers":["tnbc","her2-low-metastatic-breast-cancer"],"sections":[],"technologies":["digital-pathology-ai","adc"],"targets":["her2"],"drugs":["trastuzumab-deruxtecan"],"companies":["astrazeneca","daiichi-sankyo"],"institutions":[],"pathways":[],"terms":["her2-low","her2-ultralow","ihc"],"trials":["destiny-breast04"],"people":[],"bottlenecks":["b-biomarker-validation","b-knowledge-diffusion"],"keyPapers":["paper-schettini-her2-low-features-npj-breast-cancer-2021","paper-destiny-breast04-nejm-2022","paper-destiny-breast04-nat-med-2025-update"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Pathology-initiated re-scoring of HER2 on the diagnostic or metastatic specimen at relapse, using a standardised low-expression protocol with digital assistance, will raise the proportion of metastatic triple-negative patients recorded as HER2-low from under 25 percent to the 35 percent prevalence measured in cohorts and double the number receiving trastuzumab deruxtecan within two years.","rationale":"The drug and the approval exist; the limiting step is a score that was not designed for the decision it now makes, and the fix is a protocol and a re-read rather than a new test.","test":"Before-and-after audit across a pathology network: proportion of metastatic triple-negative cases with a documented HER2-low or HER2 0 status, concordance of re-scored versus original calls, proportion treated with trastuzumab deruxtecan; a nested validation of digital HER2 low-expression scoring against a reference panel; a prospective HER2-ultralow triple-negative cohort within the next trastuzumab deruxtecan trial.","maturity":"early-clinical","actor":"clinic","cost":"small","horizonYears":2},{"id":"idea-reg-ac225-accelerator-pharmacopoeia","kind":"idea","name":"Regional cyclotron hubs for actinium-225 with an agreed actinium-227 impurity limit","aka":[],"tldr":"Actinium-225 can be made in particle accelerators, but the product contains a trace of a long-lived impurity that regulators have not agreed how to handle. Settle the limit and build the hubs.","summary":"Proton irradiation of radium-226 yields actinium-225 with a small admixture of actinium-227 (half-life 21.8 years), while electron linac photonuclear and high-energy spallation routes differ in impurity profile. Without a harmonised monograph, each producer negotiates specifications with each regulator, slowing investment. The proposal is a joint European, US and Japanese pharmacopoeia monograph setting actinium-227 and other radionuclidic impurity limits based on dosimetry and waste handling, paired with public co-investment in three to five regional cyclotron or linac hubs sized for clinical supply.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Manufacturing cost and time for living and radioactive medicines): Hernandez, Prasad & Gellad, Total costs of chimeric antigen receptor T-cell immunotherapy (JAMA Oncology 2018)","url":"https://doi.org/10.1001/jamaoncol.2018.0977"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["targeted-alpha-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["alpha-vs-beta","dosimetry"],"trials":[],"people":[],"bottlenecks":["b-manufacturing-cell-therapy","b-regulatory-fragmentation"],"keyPapers":["paper-hernandez-jama-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A harmonised monograph published within two years is followed by at least three accelerator producers reaching GMP supply, and clinical trial sponsors report isotope supply as the limiting factor in fewer than 10% of alpha therapy trials, down from the majority today.","rationale":"Molybdenum-99 supply diversified only when regulators agreed specifications for non-HEU and accelerator-produced material. Investment follows regulatory certainty.","test":"Commission the dosimetric analysis of actinium-227 contamination at candidate limits, convene the pharmacopoeial groups, and track producer investment decisions and trial supply reports before and after publication.","maturity":"early-clinical","actor":"regulator","cost":"medium","horizonYears":3},{"id":"idea-reg-regional-radiopharmacy-hubs","kind":"idea","name":"Regional radiopharmacy hubs and harmonised transport rules for short-lived isotopes","aka":[],"tldr":"Radioactive cancer drugs decay while they travel and get stuck at borders. Regional production and simpler transport rules would get more doses to patients on time.","summary":"Radioligand therapies are often labelled centrally and shipped internationally, losing activity to decay and to customs delays; dangerous goods rules differ by country and carrier. The proposal is a network of regional GMP radiopharmacies (one per few million population) receiving bulk isotope and cold kits, labelling on demand, and delivering same-day, combined with an IAEA-brokered harmonisation of Class 7 transport paperwork and pre-clearance for medical isotopes at major airports.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Manufacturing cost and time for living and radioactive medicines): Hernandez, Prasad & Gellad, Total costs of chimeric antigen receptor T-cell immunotherapy (JAMA Oncology 2018)","url":"https://doi.org/10.1001/jamaoncol.2018.0977"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["radioligand-therapy"],"targets":[],"drugs":["pluvicto","lutathera"],"companies":[],"institutions":[],"pathways":[],"terms":["theranostics"],"trials":[],"people":[],"bottlenecks":["b-manufacturing-cell-therapy","b-global-access"],"keyPapers":["paper-hernandez-jama-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Regional labelling and pre-clearance reduce the share of radioligand doses cancelled or postponed for supply reasons from roughly 5-10% to below 1% and reduce shipped activity per delivered dose by at least a quarter.","rationale":"Nuclear medicine already runs this way for diagnostic isotopes (technetium generators, fluorine-18 cyclotron networks). Therapeutic isotopes have longer half-lives but far higher per-dose value, so the economics of regional hubs are favourable.","test":"Pilot two regional hubs in a large country and measure dose cancellation rates, shipped activity per dose and cost per dose against central supply over one year.","maturity":"early-clinical","actor":"industry","cost":"medium","horizonYears":3},{"id":"idea-acc-regional-oncology-training-hubs","kind":"idea","name":"Regional training hubs that produce oncologists, physicists and radiographers in-region","aka":[],"tldr":"Rather than sending a handful of trainees to Europe or America, build a few large training centres in Africa and South Asia that train the whole team together, with local case mix and local costs.","summary":"Specialist oncology training capacity in sub-Saharan Africa is tiny relative to need, and overseas training is expensive and leaky. Regional hubs (building on centres such as Kampala, Nairobi, Lagos, Dar es Salaam, and networks in India) would run accredited programmes across all oncology professions, with rotations, shared curricula, and remote faculty from partner institutions. Training in-region matches trainees to the diseases and constraints they will actually face.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Not enough oncologists, nurses, pathologists, physicists): Yang et al., Projected supply of and demand for oncologists and radiation oncologists through 2025 (JOP 2014)","url":"https://doi.org/10.1200/JOP.2013.001319"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["tata-memorial"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-workforce","b-global-access"],"keyPapers":["paper-yang-j-oncol-pract"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Regional hubs will graduate at least five times as many oncology professionals per dollar as overseas training, with in-country retention above 85% at five years.","rationale":"Regional medical training networks in anaesthesia and surgery (COSECSA) have shown high retention and scale; oncology can use the same governance.","test":"Establish two hubs with a ten-year funding commitment; report graduates, cost per graduate, retention, and deployment sites annually.","maturity":"being-tested-at-scale","actor":"philanthropy","cost":"large","horizonYears":6},{"id":"idea-fund-translational-institutes-gmp","kind":"idea","name":"Regional translational institutes with academic GMP suites and IND teams","aka":[],"tldr":"Build a handful of publicly-funded centres where academic discoveries can be manufactured to clinical grade and written up for regulators, so good ideas do not die for lack of a factory and a filing.","summary":"A network of five to ten regional institutes, each with GMP manufacturing for biologics, cell and gene therapies and radiopharmaceuticals, GLP toxicology partnerships, regulatory-affairs staff who write INDs and clinical trial applications, and phase 1 unit access. Academic teams apply with a candidate and leave with a first-in-human trial. Precedents include Cancer Research UK's Centre for Drug Development (which has taken dozens of academic agents into the clinic), NCATS' TRND and BrIDGs programmes, the Netherlands Cancer Institute's in-house pharmacy, and Fraunhofer's translational centres. Institutes are funded on throughput (INDs filed, trials started) and asset outcomes, not on publications.","asOf":"2026-09-08","links":[{"label":"NCATS","url":"https://ncats.nih.gov/"}],"tags":[],"related":["idea-fund-ind-enabling-fund","idea-fund-public-nonprofit-cro","idea-fund-shared-personalised-therapy-gmp"],"cancers":[],"sections":[],"technologies":["car-t","radioligand-therapy","monoclonal-antibody"],"targets":[],"drugs":[],"companies":[],"institutions":["cruk","nki","penn-abramson","nci"],"pathways":[],"terms":[],"trials":[],"people":["paul-workman"],"bottlenecks":["b-translational-valley","b-manufacturing-cell-therapy"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A national network of translational institutes triples the number of academically-originated oncology first-in-human trials per year within five years of full operation and halves the median time from candidate nomination to first patient dosed.","rationale":"CRUK's Centre for Drug Development and its predecessor have progressed many academic agents, several to approval or licensing, at costs far below industry; academic centres with in-house GMP (Penn, Baylor, NKI, Barcelona) are the places academic cell therapies actually reach patients. The binding constraint is capacity and regulatory expertise, both of which scale with dedicated funding.","test":"Fund two institutes for five years with throughput targets and compare INDs filed and time-to-first-patient for academic assets in their regions with regions without an institute.","maturity":"early-clinical","actor":"policy","cost":"large","horizonYears":5},{"id":"idea-mesothelin-car-t-regional","kind":"idea","name":"Regionally delivered mesothelin CAR-T with PD-1 blockade","aka":[],"tldr":"Deliver engineered T cells directly into the chest cavity where mesothelioma grows, and give immunotherapy to keep them working.","summary":"This idea would infuse mesothelin-directed CAR-T cells directly into the pleural cavity of patients with relapsed mesothelioma and add PD-1 blockade to keep the cells working. Mesothelin is expressed on almost all mesotheliomas, the pleural space is accessible, regional delivery avoids on-target lung toxicity, and in preclinical models CAR-T exhaustion is reversible with checkpoint blockade. A phase 1 study at Memorial Sloan Kettering Cancer Center led by Adusumilli combined intrapleural CAR-T with pembrolizumab and produced responses and some long survivors. The next step is a phase 2 with a second-line control and an armoured CAR-T arm; at an early clinical stage, it addresses the bottleneck of cold tumours and the idea of treating the body cavity rather than the bloodstream.","asOf":"2026-09-07","links":[{"label":"Adusumilli et al., Phase 1 trial of regional mesothelin-targeted CAR T-cell therapy with pembrolizumab in malignant pleural disease (Cancer Discovery 2021)","url":"https://doi.org/10.1158/2159-8290.CD-21-0407"}],"tags":[],"related":[],"cancers":["mesothelioma"],"sections":[],"technologies":["car-t","armored-car"],"targets":["mesothelin","pd1"],"drugs":[],"companies":[],"institutions":["mskcc"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-adusumilli-cancer-discov","paper-mesothelin-mesothelioma-cancer-discov-2016","paper-mesothelin-mesothelioma-clin-cancer-res-2004","paper-mesothelin-mesothelioma-j-clin-oncol-2016"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Intrapleural mesothelin CAR-T plus PD-1 blockade achieves median OS beyond 24 months in relapsed mesothelioma, exceeding historical second-line outcomes.","rationale":"Mesothelin is near-universally expressed; the pleural space is accessible; CAR-T exhaustion is reversible with checkpoint blockade in preclinical models.","test":"Phase 2 with a contemporaneous control (second-line chemotherapy or nivolumab), OS endpoint; armoured (PD-1 dominant-negative) CAR-T variant as a second arm.","maturity":"early-clinical"},{"id":"idea-tr2-preclinical-registered-reports","kind":"idea","name":"Registered reports for cancer biology: the plan is peer-reviewed before the result","aka":[],"tldr":"Journals agree to publish a study based on the quality of the question and plan, before anyone knows the answer. That removes the pressure to make results look positive.","summary":"Registered reports, adopted by over 300 journals mostly in psychology and neuroscience, reduce positive-result bias dramatically (around 44% positive results versus over 90% in conventional articles in one analysis). Cancer biology journals have barely adopted the format. A concerted push by the major cancer journals to offer registered reports for confirmatory preclinical studies (the last experiment before an investigational new drug application, for instance) would change the incentive at the point where it matters most for translation.","asOf":"2026-09-08","links":[{"label":"Registered Reports (Center for Open Science)","url":"https://www.cos.io/initiatives/registered-reports"}],"tags":[],"related":["idea-tr2-biomarker-study-registry","idea-tr2-negative-results-journal"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-reproducibility","b-negative-results"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Registered reports in cancer biology will report a positive-result rate below 60%, compared with above 85% in matched conventional articles, and their findings will replicate at a higher rate.","rationale":"The format directly removes the mechanisms of bias: outcome switching, selective reporting and publication bias.","test":"Three cancer journals launch the format; compare positive-result rates and replication of the first 100 registered reports with matched conventional papers.","maturity":"early-clinical","actor":"research","cost":"small","horizonYears":2},{"id":"idea-prev-mced-registry-randomised","kind":"idea","name":"Registry-based randomised MCED trial: a million people, no study visits","aka":[],"tldr":"Randomise people through the national health system, post the blood kit, and read cancer deaths off the registry. That is ten times cheaper per participant than a classic trial.","summary":"Swedish registry-based RCTs (TASTE, DETO2X) showed pragmatic randomisation at national scale at a fraction of usual cost. Propose an MCED trial that randomises through screening call/recall, draws blood at existing phlebotomy or mobile units, and uses cancer registry and death-certificate linkage for endpoints, with no in-person study visits.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The hardest cancers are found late): Crosby et al., Early detection of cancer (Science 2022)","url":"https://doi.org/10.1126/science.aay9040"}],"tags":[],"related":[],"cancers":[],"sections":["early-detection"],"technologies":["mced"],"targets":[],"drugs":[],"companies":[],"institutions":["karolinska"],"pathways":[],"terms":["stage-shift"],"trials":[],"people":[],"bottlenecks":["b-early-detection","b-trial-enrolment"],"keyPapers":["paper-crosby-science"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A registry-based RCT of at least one million adults aged 50-79 can detect a 15% relative reduction in cancer mortality within eight years at under $50 per participant-year.","rationale":"MCED effects on all-cancer mortality will be modest and need very large samples; only registry-linked pragmatic designs make that affordable.","test":"Feasibility pilot in a Nordic country or NHS region (100,000 invitations, mailed kits; uptake and linkage completeness as endpoints), then scale.","maturity":"speculative","actor":"research","cost":"large","horizonYears":8},{"id":"idea-data-registry-based-rcts","kind":"idea","name":"Registry-based randomised trials for oncology comparative effectiveness","aka":[],"tldr":"Use the cancer registry itself as the trial machine: randomise patients at diagnosis, then let the registry collect the outcomes for a fraction of the usual cost.","summary":"Registry-based randomised trials (R-RCTs), pioneered in Swedish cardiology, use the registry for identification, randomisation and outcome follow-up. Oncology has the registries (Nordic, England, Netherlands) but almost no R-RCTs. The proposal funds a programme of five R-RCTs on high-value comparative questions with routine endpoints (surveillance intervals, adjuvant duration, supportive care) and develops the ethics and consent templates to make the design routine.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Weak real-world evidence and registries): Gyawali, Hey & Kesselheim, Assessment of the clinical benefit of cancer drugs receiving accelerated approval (JAMA Intern Med 2019)","url":"https://doi.org/10.1001/jamainternmed.2019.0462"}],"tags":[],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["karolinska"],"pathways":[],"terms":["real-world-evidence"],"trials":[],"people":[],"bottlenecks":["b-real-world-evidence","b-trial-design","b-trial-enrolment"],"keyPapers":["paper-gyawali-jama-intern-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"R-RCTs will answer comparative effectiveness questions with 2,000 or more patients at under 500 dollars per patient and within three years, roughly a tenth of conventional trial cost.","rationale":"TASTE randomised 7,244 patients for a small fraction of a conventional trial budget; oncology questions about duration, schedule and surveillance have equally routine endpoints.","test":"Run one R-RCT in a Nordic or English registry (for example, imaging surveillance every six versus twelve months after curative colorectal surgery) and report cost, enrolment and completeness of outcomes.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":4},{"id":"idea-tr2-pragmatic-sequence-randomisation","kind":"idea","name":"Registry-embedded randomisation of treatment order in routine care","aka":[],"tldr":"When two approved drugs are both reasonable next steps and nobody knows which should come first, let the clinic flip a coin and record what happens.","summary":"Point-of-care randomisation embedded in the electronic record (as in the TASTE trial in cardiology and the NHS PRINCIPLE platform) can answer sequencing questions about approved drugs with thousands of patients at low cost. Consent is simplified because both options are standard of care; follow-up uses routine data.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Too many combinations to test): Palmer & Sorger, Combination cancer therapy can confer benefit via patient-to-patient variability without drug additivity or synergy (Cell 2017)","url":"https://doi.org/10.1016/j.cell.2017.11.009"}],"tags":[],"related":["idea-tr2-smart-sequencing-adc"],"cancers":["breast-hr-positive"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["real-world-evidence","adc-sequencing"],"trials":[],"people":[],"bottlenecks":["b-combination-space","b-real-world-evidence"],"keyPapers":["paper-palmer-cell"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A registry-embedded randomisation of sequence (for example CDK4/6 inhibitor then oral SERD versus the reverse) enrols at least ten times faster per site than a conventional sequencing trial and yields a survival comparison with adequate power within four years.","rationale":"Cardiology and infectious disease have used registry-randomised trials at scale. Oncology has the registries (national cancer registries, Flatiron-type databases) but has not embedded randomisation.","test":"Pilot in one national health system for one sequencing question where equipoise is documented in guidelines; measure enrolment rate and data completeness.","maturity":"speculative","actor":"clinic","cost":"medium","horizonYears":4},{"id":"idea-prev-precursor-endpoints-for-approval","kind":"idea","name":"Regulators accept shrinking of precancer as the endpoint for prevention drug approval","aka":[],"tldr":"Few companies develop cancer prevention drugs because trials take decades. If regulators accepted validated precancer endpoints, as they do cholesterol for heart disease, industry would return.","summary":"Few companies develop cancer prevention drugs because trials take decades, so this idea asks regulators to accept validated precursor endpoints, such as CIN2+, colorectal adenoma, Barrett's dysplasia and oral leukoplakia regression, for conditional approval with mandated long-term cancer incidence follow-up. Statin and antihypertensive development depended on surrogate endpoints, and cancer prevention has none accepted despite established links between these precursors and cancer risk. The aim is a large increase in industry-sponsored chemoprevention trials. The test is FDA and EMA guidance followed by counting trials registered before and after. Speculative in maturity, it addresses the bottlenecks Prevention we already have is not deployed and Trial design, endpoints and cost.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Prevention we already have is not deployed): Islami et al., Proportion of cancer attributable to modifiable risk factors (CA 2018)","url":"https://doi.org/10.3322/caac.21440"}],"tags":[],"related":[],"cancers":[],"sections":["prevention"],"technologies":["chemoprevention"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["accelerated-approval"],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption","b-trial-design"],"keyPapers":["paper-islami-ca-cancer-j-clin"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A precursor-endpoint pathway triples the number of industry-sponsored chemoprevention trials within five years.","rationale":"Statin and antihypertensive development depended on surrogate endpoints; cancer prevention has none accepted.","test":"FDA and EMA guidance, then count trials registered before and after.","maturity":"speculative","actor":"regulator","cost":"small","horizonYears":4},{"id":"idea-tr2-cdx-mutual-recognition","kind":"idea","name":"Regulators recognise each other's companion diagnostic approvals","aka":[],"tldr":"A test approved to select patients for a drug in the US must go through separate approval in Europe, Japan and elsewhere, delaying the drug. Accepting each other's test approvals would fix the delay.","summary":"Companion diagnostics are regulated separately from drugs and differently by region (FDA premarket approval, EU IVDR, PMDA). Divergence delays drug access and multiplies bridging studies. A mutual-recognition agreement for companion diagnostics among ICH-aligned regulators, analogous to Project Orbis for drugs, with a shared analytical validation dossier and a single bridging-study standard, would remove months to years of delay.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Biomarkers are not validated or standardised): Fernandez et al., Examination of low ERBB2 protein expression in breast cancer tissue (JAMA Oncology 2022)","url":"https://doi.org/10.1001/jamaoncol.2021.7239"}],"tags":[],"related":["foundation-medicine","foundationone-cdx"],"cancers":[],"sections":[],"technologies":["companion-diagnostic"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["companion-diagnostic-term"],"trials":[],"people":[],"bottlenecks":["b-biomarker-validation","b-regulatory-fragmentation"],"keyPapers":["paper-fernandez-jama-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Mutual recognition reduces the median lag between drug approval and companion diagnostic availability in the second region from over a year to under three months.","rationale":"Project Orbis and the Access Consortium show that regulators can share reviews; analytical validation of a test is less region-dependent than clinical practice.","test":"Pilot recognition of five companion diagnostics between two regulators and measure time to availability against contemporaneous non-pilot tests.","maturity":"speculative","actor":"regulator","cost":"small","horizonYears":3},{"id":"idea-tr1-remote-consent-tele-screening","kind":"idea","name":"Remote consent and tele-screening so the first trial visit is a video call","aka":[],"tldr":"Much of trial screening is paperwork, questions and reviewing scans that already exist. Doing this by video and electronic consent before any travel would let patients decide without a wasted trip.","summary":"Sites adopt electronic consent with teach-back, tele-screening visits reviewing existing imaging and pathology via central read, and remote collection of history and performance status, so in-person attendance is needed only for procedures the protocol genuinely requires. Regulators in the US and EU accept eConsent; adoption in oncology remains low.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Trials enrol too few, too slowly): Unger et al., Systematic review of barriers to cancer trial participation (JNCI 2019)","url":"https://doi.org/10.1093/jnci/djy221"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["nci"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-enrolment"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Sites offering remote consent and screening will convert a higher fraction of referred patients into enrolled patients and shorten the interval from referral to cycle 1 day 1.","rationale":"Screen failure after travel is demoralising and expensive; many failures could be identified from existing records. Remote consent lets patients involve family and take time, which improves comprehension.","test":"Stepped-wedge rollout across a cooperative group's sites; measure referral-to-enrolment conversion and time to first dose before and after.","maturity":"early-clinical","actor":"clinic","cost":"small","horizonYears":1},{"id":"idea-tr1-disability-and-mental-illness-inclusion","kind":"idea","name":"Remove blanket exclusions for mental illness and dementia; support consent instead","aka":[],"tldr":"People with serious mental illness or dementia are routinely excluded from cancer trials by vague compliance clauses, though they get cancer just as often and do worse. Replacing those clauses with assessable criteria, and funding supported consent and accommodations such as longer visits, would let them take part.","summary":"Protocols replace 'psychiatric illness that would interfere with compliance' and similar clauses with specific, assessable criteria; supported decision-making, legally authorised representative consent where appropriate, and accommodations (longer visits, carer involvement, simplified materials) are funded. Enrolment and outcomes for these groups are reported.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Trials do not represent the people who get cancer): Loree et al., Disparity of race reporting and representation in trials leading to cancer drug approvals (JAMA Oncology 2019)","url":"https://doi.org/10.1001/jamaoncol.2019.1870"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["nci"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-diversity","b-trial-enrolment"],"keyPapers":["paper-loree-jama-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Removing blanket exclusions with supported consent will enrol patients with psychiatric or cognitive conditions at a rate closer to their prevalence among cancer patients without increased protocol deviations attributable to the condition.","rationale":"People with serious mental illness have higher cancer mortality and are near-absent from trials; the exclusion is habitual, not evidence-based. Dementia trials show supported consent works.","test":"Audit exclusion language in current protocols; pilot the replacement criteria at psychiatric-liaison-supported cancer centres and measure enrolment and deviation rates.","maturity":"speculative","actor":"industry","cost":"small","horizonYears":2},{"id":"idea-prev-opportunistic-salpingectomy-default","kind":"idea","name":"Remove the fallopian tubes during any pelvic surgery once childbearing is finished","aka":[],"tldr":"Most ovarian cancers start in the fallopian tubes. Removing the tubes at hysterectomy, or instead of tying them, as British Columbia has done, appears to prevent ovarian cancer.","summary":"Most ovarian cancers start in the fallopian tubes, so this idea makes salpingectomy the default at hysterectomy and in place of tubal ligation for permanent contraception in all health systems, once childbearing is finished. British Columbia's opportunistic salpingectomy programme shows reduced serous ovarian cancer incidence in early follow-up, there is no known effect on ovarian function, and salpingectomy is also a more effective sterilisation than ligation. The aim is fewer high-grade serous ovarian cancers in the exposed cohort. The test is registry-based cohort comparisons across adopting jurisdictions. Being tested at scale, it addresses the bottleneck Prevention we already have is not deployed and sits in the prevention and surgery sections.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Prevention we already have is not deployed): Islami et al., Proportion of cancer attributable to modifiable risk factors (CA 2018)","url":"https://doi.org/10.3322/caac.21440"}],"tags":[],"related":[],"cancers":["ovarian"],"sections":["prevention","surgery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption"],"keyPapers":["paper-islami-ca-cancer-j-clin"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Programme-wide opportunistic salpingectomy reduces high-grade serous ovarian cancer incidence by at least 40% in the exposed cohort at 15 years.","rationale":"Tubal origin of high-grade serous cancer; no known effect on ovarian function; salpingectomy is also a more effective sterilisation than ligation.","test":"Run registry-based cohort comparisons across adopting jurisdictions.","maturity":"being-tested-at-scale","actor":"clinic","cost":"small","horizonYears":8},{"id":"idea-tr1-pk-informed-organ-thresholds","kind":"idea","name":"Replace fixed kidney and liver cut-offs with drug-specific, pharmacology-based thresholds","aka":[],"tldr":"Most trials copy the same kidney and liver cut-offs, such as creatinine clearance above 60, regardless of how the drug is cleared. Setting each threshold from the drug's own clearance route and organ-impairment pharmacokinetic studies would let patients with mild organ impairment join safely instead of being excluded.","summary":"Organ-function eligibility criteria (creatinine clearance, bilirubin, transaminases) would be set per drug from its clearance route and the results of early organ-impairment pharmacokinetic studies, rather than the default 'creatinine clearance above 60 ml/min' copied between protocols. Drugs with negligible renal clearance would have no renal cut-off; drugs with hepatic clearance would have a dose-adjusted cohort instead of an exclusion.","asOf":"2026-09-08","links":[{"label":"FDA: Eligibility Criteria: Patients with Organ Dysfunction or Prior or Concurrent Malignancies","url":"https://www.fda.gov/regulatory-information/search-fda-guidance-documents/cancer-clinical-trial-eligibility-criteria-patients-organ-dysfunction-or-prior-or-concurrent"}],"tags":[],"related":[],"cancers":["multiple-myeloma","urothelial","rcc"],"sections":[],"technologies":["monoclonal-antibody","adc"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-enrolment","b-dose-optimisation","b-aging-comorbidity"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Pharmacology-based thresholds will make at least 10-20 percent more patients eligible in older-skewed cancers without increasing dose-limiting toxicity, and will produce label dosing guidance for organ impairment at the time of approval rather than years later.","rationale":"Renal impairment is common in patients over 70 and in myeloma, bladder and kidney cancer; many modern agents (monoclonal antibodies, most ADCs) are not renally cleared, so the criterion excludes without protecting. The FDA organ-dysfunction eligibility guidance supports this approach.","test":"A sponsor applies PK-informed thresholds across its oncology portfolio for two years and reports the eligible fraction, DLT rates and organ-impairment sub-cohort outcomes versus its historical protocols.","maturity":"speculative","actor":"industry","cost":"small","horizonYears":3},{"id":"idea-prev-hcc-blood-surveillance-cirrhosis","kind":"idea","name":"Replace six-monthly ultrasound with a blood test for liver cancer in cirrhosis","aka":[],"tldr":"People with cirrhosis are meant to have ultrasound scans twice a year, but most do not. A blood test done with their routine liver bloods could catch liver cancer earlier.","summary":"GALAD and methylation or protein panels show sensitivity above ultrasound for early hepatocellular carcinoma, while adherence to ultrasound surveillance is under 30% in most reported settings. Propose a randomised trial of blood-based surveillance (MRI for positives) versus ultrasound, with early-stage detection and adherence as endpoints.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The hardest cancers are found late): Crosby et al., Early detection of cancer (Science 2022)","url":"https://doi.org/10.1126/science.aay9040"}],"tags":[],"related":[],"cancers":["hcc"],"sections":["early-detection"],"technologies":["liquid-biopsy","ultrasound","mri"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-early-detection"],"keyPapers":["paper-crosby-science"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Blood-based surveillance increases early-stage (BCLC 0/A) HCC detection by at least 20 percentage points, driven primarily by adherence.","rationale":"A test that rides on existing blood draws removes the main failure point, which is attending for imaging.","test":"Run a 3,000-patient RCT in cirrhosis clinics with a three-year endpoint.","maturity":"early-clinical","actor":"clinic","cost":"medium","horizonYears":4},{"id":"idea-prostate-other-cause-mortality-as-a-reported-service-outcome","kind":"idea","name":"Report death from other causes as an outcome of the prostate cancer service, split by deprivation and ethnicity","aka":["other-cause mortality prostate service outcome","competing mortality prostate cancer equity"],"tldr":"When Black and white men in the United States are given the same treatment, the gap in dying of prostate cancer largely closes. The gap in dying of everything else does not. Cancer services measure the first and not the second, which means the surviving disparity is invisible to the people best placed to act on it.","summary":"Dess and colleagues pooled three cohorts with progressively tighter control of access: a registry, an equal-access surgical system and four randomised radiotherapy trials. After inverse probability weighting, the prostate cancer-specific hazard for Black men fell from 1.30 to 1.09 in the registry, was not significantly different in the equal-access cohort, and was significantly lower in the trial cohort. Other-cause mortality remained significantly higher in two of the three cohorts, at subdistribution hazard ratios of 1.30 and 1.17.\n\nThat pattern has a direct operational meaning. A prostate cancer service that achieves equal treatment has done most of what it can about prostate cancer death and none of what it could about the larger remaining gap. The men in question are on androgen deprivation, which causes weight gain, insulin resistance, dyslipidaemia, loss of bone and muscle and, in some analyses, cardiovascular events; they are seen regularly by the cancer service for years; and their cardiovascular and metabolic risk is managed, if at all, elsewhere. The proposal is narrow and measurable: report other-cause mortality alongside cancer-specific mortality in every prostate cancer service audit, split by deprivation quintile and ethnicity, and make it the outcome against which a hormone therapy cardiometabolic clinic is judged.\n\nWhat any of this means for someone treated in Britain, from the screening committee's position and the NICE appraisals to scanner and radiotherapy capacity, waiting times and how to reach a trial, is on the UK and NHS pathway page for prostate cancer.","asOf":"2026-09-25","links":[],"tags":["prostate-evidence"],"related":["idea-acc-cardiometabolic-clinic-hormone-therapy","idea-exercise-as-adjuvant","idea-acc-risk-stratified-follow-up","survivorship-roadmap","prostate-roadmap"],"cancers":["prostate","prostate-intermediate-risk","prostate-high-risk","prostate-mhspc","prostate-nmcrpc"],"sections":["supportive-care","hormonal","nutrition-lifestyle"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["adt","quality-of-life","other-cause-mortality","intermittent-androgen-deprivation"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-global-access","b-aging-comorbidity","b-real-world-evidence","b-care-fragmentation","b-trial-diversity"],"keyPapers":["paper-dess-black-race-prostate-mortality-jama-oncol-2019","paper-conti-trans-ancestry-gwas-prostate-nat-genet-2021","paper-hussain-swog-9346-intermittent-androgen-deprivation-nejm-2013","paper-langley-lancet","paper-uspstf-prostate-screening-jama-2018"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Making other-cause mortality a reported and audited outcome of prostate cancer services, split by deprivation and ethnicity, will reveal a larger equity gap than cancer-specific mortality does and will support cardiometabolic intervention embedded in the cancer clinic that narrows it, at a cost per life-year lower than most systemic anticancer therapy in the same disease.","rationale":"Prostate cancer has an unusual competing-risk structure: most men diagnosed with it die of something else, and androgen deprivation, the backbone of treatment, is itself a cardiometabolic intervention in the wrong direction. Dess supplies the measurement that separates the two gaps, and shows that the one cancer services already work on largely closes under equal access while the other does not. Nothing in a standard cancer audit captures this, because cancer audits are built around cancer-specific outcomes on the reasonable ground that other deaths are not the service's doing. In a disease treated for a decade with a drug that worsens metabolic health, that reasoning no longer holds.","test":"Add other-cause mortality, split by deprivation quintile and by ethnicity, to national prostate cancer audit reporting, using registry linkage to death certification, and publish it alongside cancer-specific mortality by provider. Then run a cluster-randomised trial in which intervention sites embed cardiometabolic assessment and treatment into the androgen deprivation follow-up appointment (blood pressure, lipids, HbA1c, bone density, structured exercise referral) and control sites continue usual referral to primary care, with other-cause mortality at five years as the primary endpoint and cardiovascular events at two years as the interim readout. Reporting can start immediately; the trial takes five years.","maturity":"early-clinical","actor":"policy","cost":"medium","horizonYears":5},{"id":"idea-gbc-report-gallbladder-separately-in-biliary-trials","kind":"idea","name":"Report gallbladder cancer as its own population in every biliary trial","aka":[],"tldr":"Every drug gallbladder cancer patients receive was tested in mixed bile duct trials where they were a subgroup. Requiring trials to pre-specify and publish gallbladder results, with a minimum number enrolled, would give the disease its own evidence at almost no cost.","summary":"ABC-02, BILCAP, ABC-06, TOPAZ-1 and KEYNOTE-966 enrolled gallbladder cancer alongside intrahepatic and extrahepatic cholangiocarcinoma and reported it, if at all, in forest plots. Yet the diseases differ: HER2 positivity runs at 9 to 20 percent in gallbladder and extrahepatic cancers against 5 percent intrahepatic; immune profiles differ by population; and the UK CAPBIL cohort saw no adjuvant benefit in a mostly gallbladder population. A reporting standard (pre-specified gallbladder stratum, minimum enrolment, mandatory subgroup publication) could be asked of sponsors by regulators and journals and would cost the trials almost nothing.","asOf":"2026-09-24","links":[{"label":"Galdy et al.: HER2 in biliary tract cancers by site (Cancer Metastasis Rev 2017)","url":"https://europepmc.org/article/MED/27981460"},{"label":"Zhu et al.: population-specific immunogenomics of gallbladder cancer (Mod Pathol 2025)","url":"https://europepmc.org/article/MED/40541865"}],"tags":["gallbladder-evidence"],"related":[],"cancers":["gallbladder","biliary-tract-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["hazard-ratio"],"trials":["topaz-1","keynote-966","bilcap","abc-06","acticca-1","nct06109779"],"people":[],"bottlenecks":["b-rare-cancers","b-trial-design","b-negative-results"],"keyPapers":["paper-galdy-her2-biliary-tract-meta-analysis-cancer-metastasis-rev-2017","paper-zhu-population-specific-immunogenomics-gallbladder-cancer-mod-pathol-2025","paper-mcclements-capbil-surgical-outcomes-gallbladder-cancer-hpb-2026"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Mandating a pre-specified gallbladder cancer stratum with published results in biliary tract cancer trials will reveal clinically meaningful differences in treatment effect between gallbladder cancer and cholangiocarcinoma within five years.","rationale":"Prevalence of HER2, immune profile and recurrence pattern already differ between sites; pooled analyses hide effect modification. The cost of a stratum is small; the cost of a wrong extrapolation is borne by every gallbladder patient.","test":"Retrospective: obtain gallbladder-stratum results from TOPAZ-1, KEYNOTE-966, BILCAP and ABC-06 and test for interaction with site. Prospective: ACTICCA-1 and ARTEMIDE-Biliary01 publish gallbladder strata as primary-paper tables.","maturity":"speculative","actor":"regulator","cost":"small","horizonYears":3},{"id":"lymphoma-ev-manufacturing-time-as-a-trial-endpoint","kind":"idea","name":"Report the time from apheresis to infusion as a trial endpoint, not a logistics footnote","aka":["Vein-to-vein time as a CAR-T endpoint","Manufacturing interval in cell therapy trials"],"tldr":"The best explanation for why one second-line CAR-T trial failed when two succeeded is how long the cells took to make. That interval is almost never a reported endpoint.","summary":"This is a cheap idea with a large effect on interpretation. The cross-trial inference that manufacturing time explains BELINDA is the best available explanation for a 322-patient randomised failure, and it remains an inference because the data to test it were not collected as endpoints. Rapid-manufacture and point-of-care products are entering trials now, which makes the measurement urgent rather than retrospective.","asOf":"2026-10-01","links":[],"tags":["lymphoma-evidence"],"related":["lymphoma-roadmap"],"cancers":["dlbcl","non-hodgkin-lymphoma","follicular-lymphoma"],"sections":["cell-therapy"],"technologies":["car-t"],"targets":[],"drugs":["axicabtagene-ciloleucel","tisagenlecleucel","lisocabtagene-maraleucel"],"companies":[],"institutions":[],"pathways":[],"terms":["bridging-therapy","lymphodepletion","lymphoma-tx-car-t-pathway"],"trials":["belinda","zuma-7","transform","transcend-nhl-001"],"people":[],"bottlenecks":["b-manufacturing-cell-therapy","b-trial-design","b-real-world-evidence"],"keyPapers":["paper-belinda-tisagenlecleucel-second-line-nejm-2022","paper-transcend-nhl-001-liso-cel-lancet-2020","paper-zuma-7-axi-cel-second-line-nejm-2022"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"The interval between apheresis and infusion, and what is given during it, is a determinant of CAR-T outcome large enough to change trial results, and reporting it as a prespecified endpoint would improve both trial interpretation and clinical delivery.","rationale":"BELINDA randomised 322 patients to tisagenlecleucel or salvage chemotherapy with transplant in the second line and found median event-free survival of 3.0 months in both arms, while ZUMA-7 and TRANSFORM, testing the other two products in the same setting, were positive. The median time from leukapheresis to infusion in BELINDA was 52 days, and 25.9 per cent of the CAR-T group had progressed by week 6 against 13.8 per cent of the comparator group. TRANSCEND NHL 001 reported that 75 of 344 patients who underwent leukapheresis never received the product, which is attrition a response rate does not show.","test":"Require trials of autologous cell therapy to prespecify and report the distribution of the apheresis-to-infusion interval, the proportion of enrolled patients who never receive the product and why, and an intention-to-treat analysis from apheresis rather than from infusion. Then test, in a randomised comparison or a registry with sufficient variation, whether shortening the interval improves outcomes.","maturity":"early-clinical","actor":"regulator","cost":"small","horizonYears":4},{"id":"idea-moon-time-toxicity-reporting","kind":"idea","name":"Report time toxicity, the days a treatment consumes, in every trial and decision aid","aka":[],"tldr":"Alongside how many months a treatment adds, patients should be told how many days it takes from them in clinics, infusions, scans and recovery.","summary":"Time toxicity (days with in-person healthcare contact) has been proposed as a formal endpoint and, when reanalysed from trials of drugs offering weeks of benefit, can consume much of the survival gain. The proposal is that trials report days at home versus days in contact with healthcare for each arm, that regulators and guideline bodies display it, and that decision aids present it alongside survival and side-effects.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Patients lack understanding, navigation and agency): Basch et al., Overall survival results of a trial assessing patient-reported outcomes for symptom monitoring during routine cancer treatment (JAMA 2017)","url":"https://doi.org/10.1001/jama.2017.7156"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["os","pfs"],"trials":[],"people":[],"bottlenecks":["b-patient-voice","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"When time toxicity is presented, a meaningful share of patients with marginal-benefit palliative treatments choose differently, and sponsors design regimens with fewer visits.","rationale":"Patients weigh time differently from clinicians; the metric is computable from trial case report forms already collected.","test":"Reanalyse ten recent pivotal trials to report time toxicity; then randomise presentation of the metric in a decision-aid study and measure choice and regret.","maturity":"early-clinical","actor":"research","cost":"small","horizonYears":2},{"id":"idea-acc-time-toxicity-reporting","kind":"idea","name":"Report time toxicity, the days spent in healthcare, as a standard outcome for older patients","aka":[],"tldr":"A treatment that adds two months of life but takes up most of those days in hospitals and clinics may not be worth it to an older patient. Trials should report how many days treatment consumes.","summary":"Time toxicity, the number of days with physical healthcare contact, has been proposed as a patient-relevant outcome that is easily measurable from trial and administrative data. For older patients with limited survival, it may outweigh modest survival gains. Requiring its reporting in trials and in real-world evaluations of new therapies would inform shared decisions and could change the perceived value of some regimens.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Older and multimorbid patients are excluded and undertreated): Mohile et al., Evaluation of geriatric assessment and management on toxic effects of cancer treatment (GAP70+, Lancet 2021)","url":"https://doi.org/10.1016/S0140-6736(21)01789-X"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["os","pfs"],"trials":[],"people":[],"bottlenecks":["b-aging-comorbidity","b-toxicity-qol","b-trial-design"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Time toxicity will vary by more than fourfold between regimens with similar survival in the same indication, and presenting it in decision aids will change treatment choice for a measurable fraction of older patients.","rationale":"Days at home is a validated, patient-valued outcome in other fields; oncology has the data to compute it but does not report it.","test":"Retrospectively compute time toxicity for ten registration trials; then a randomised study of decision aids with and without time-toxicity information in patients over 75.","maturity":"speculative","actor":"research","cost":"small","horizonYears":2},{"id":"idea-bio2-trem2-myeloid-reprogramming","kind":"idea","name":"Reprogramme suppressive macrophages instead of trying to delete them","aka":[],"tldr":"Tumours fill with immune cells that protect them. Earlier drugs tried to remove those cells and failed. Newer ones aim to switch them to the attacking side.","summary":"CSF1R inhibitors depleted macrophages broadly and produced little benefit outside tenosynovial giant cell tumour, plausibly because depletion removes useful cells alongside harmful ones. TREM2, MARCO and LILRB2 mark specific suppressive macrophage states in human tumour single-cell atlases, and antibodies against them are in early trials. The proposition is state-switching, verified by on-treatment biopsies, rather than depletion.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Cold tumours and the immunosuppressive microenvironment): Haslam & Prasad, Estimation of the percentage of US patients eligible for and responding to checkpoint inhibitors (JAMA Netw Open 2019)","url":"https://doi.org/10.1001/jamanetworkopen.2019.2535"}],"tags":[],"related":[],"cancers":["pancreatic","colorectal","glioblastoma"],"sections":[],"technologies":["single-cell-spatial","checkpoint-inhibitor","monoclonal-antibody"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["cold-vs-hot"],"trials":[],"people":["caetano-reis-e-sousa"],"bottlenecks":["b-tme-immunosuppression","b-immunotherapy-response"],"keyPapers":["paper-haslam-jama-netw-open"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Blockade of a suppressive macrophage state marker shifts the intratumoural myeloid transcriptional programme towards antigen presentation and raises response to checkpoint blockade in tumours pre-selected for high suppressive macrophage content.","rationale":"Human single-cell data consistently identify TREM2-high macrophage states in poorly responding tumours, and genetic ablation in mice restores checkpoint response. Selecting patients by myeloid content, rather than treating everyone, is the step the CSF1R programmes skipped.","test":"A biopsy-mandated phase 2 in myeloid-high tumours with paired pre- and on-treatment single-cell profiling; kill the programme if the myeloid state does not shift, regardless of response rate.","maturity":"early-clinical","actor":"industry","cost":"medium","horizonYears":6},{"id":"idea-bio2-liver-niche-kupffer-reprogramming","kind":"idea","name":"Reprogramme the liver's own immune cells to refuse metastases","aka":[],"tldr":"The liver is where bowel cancer most often spreads. Drugs delivered straight into the liver's blood supply could retrain its resident immune cells to reject arriving cancer cells.","summary":"Kupffer cells and liver sinusoidal endothelium determine whether arriving colorectal cells die or seed, and hepatic arterial infusion is an established delivery route with dedicated pumps and an experienced clinical community. Combining regional delivery with a myeloid agonist (CD40 agonist, TLR9 agonist or STING agonist) targets the niche rather than the tumour, at doses that would be intolerable systemically.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Metastasis is understood least and studied last): Dillekås et al., Are 90% of deaths from cancer caused by metastases? (Cancer Medicine 2019)","url":"https://doi.org/10.1002/cam4.2474"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":[],"technologies":["sting-agonist","radioembolisation-tare"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["oligometastatic"],"trials":[],"people":[],"bottlenecks":["b-metastasis-biology","b-tme-immunosuppression"],"keyPapers":["paper-dillekas-cancer-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Regional hepatic delivery of a myeloid-agonist regimen after resection of colorectal liver metastases reduces the new-hepatic-lesion rate at 18 months compared with systemic therapy alone.","rationale":"Regional floxuridine infusion already improves liver-specific outcomes, proving the route matters. CD40 agonism converts liver macrophages to an anti-tumour state in murine colorectal liver metastasis models, and systemic CD40 agonists are limited mainly by hepatotoxicity and cytokine release.","test":"Dose-finding regional infusion study with paired liver biopsies for myeloid phenotype, then a randomised trial with new-hepatic-lesion-free survival as primary endpoint.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":7},{"id":"idea-pdac-stromal-reprogramming-not-depletion","kind":"idea","name":"Reprogramme the stroma rather than remove it: second-generation stromal trials with a stromal biomarker and a survival endpoint","aka":[],"tldr":"Pancreatic tumours are mostly scar tissue. The first attempt to dissolve it, an enzyme given with chemotherapy to nearly 500 patients, shrank more tumours but did not lengthen life, and mouse work showed that stripping out the scar-forming cells made cancers worse. The proposal is to test drugs that change what the stroma does rather than remove it, in trials measured on survival.","summary":"HALO-301 (2020) selected hyaluronan-high patients, added pegvorhyaluronidase alfa to gemcitabine and nab-paclitaxel and produced a higher response rate (47 versus 36 percent) with identical survival (11.2 versus 11.5 months); development stopped. Özdemir (2014) had shown that deleting alpha-SMA myofibroblasts in mice produced undifferentiated, hypoxic, immunosuppressed tumours and shorter survival, reversible by anti-CTLA4 but not gemcitabine, and that fewer myofibroblasts in human tumours also meant worse survival. Moffitt (2015) showed the stroma itself has prognostic subtypes (normal versus activated). The lesson is that the stroma is heterogeneous and partly restraining, so the target is its activated, immunosuppressive state rather than its mass: candidate approaches include FAP-directed agents (imaging and radioligands exist), TGF-beta pathway modulation and vitamin D receptor or other fibroblast-reprogramming agents, combined with RAS inhibition or chemotherapy. The design requirement is a stromal biomarker at entry and on treatment (activated stroma signature or FAP PET), randomisation against the same backbone, and overall survival rather than response as the endpoint, because response without survival is the failure mode this field has already seen.","asOf":"2026-09-24","links":[{"label":"HALO 109-301 (JCO 2020)","url":"https://europepmc.org/article/MED/32706635"},{"label":"Özdemir et al.: fibroblast depletion accelerates pancreas cancer (Cancer Cell 2014)","url":"https://europepmc.org/article/MED/24856586"}],"tags":["pancreatic-evidence"],"related":["idea-fap-theranostics-pancancer"],"cancers":["pancreatic","metastatic-pdac"],"sections":[],"technologies":["fapi-pet"],"targets":["fap"],"drugs":[],"companies":[],"institutions":[],"pathways":["tgf-beta","emt"],"terms":["desmoplasia","desmoplastic-stroma-rich","cancer-associated-fibroblasts","cold-vs-hot"],"trials":[],"people":[],"bottlenecks":["b-tme-immunosuppression","b-negative-results","b-preclinical-models"],"keyPapers":["paper-halo-301-pegvorhyaluronidase-jco-2020","paper-ozdemir-caf-depletion-accelerates-pancreatic-cancer-cancer-cell-2014","paper-moffitt-virtual-microdissection-subtypes-nat-genet-2015"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"In activated-stroma pancreatic cancer, a fibroblast-reprogramming agent added to a RAS inhibitor or chemotherapy backbone improves overall survival (hazard ratio 0.75 or better) where matrix depletion did not, and the benefit tracks conversion of the stromal signature on treatment.","rationale":"Depletion failed and can harm; the stroma's prognostic subtypes show it has states that can be measured and, in models, shifted; RAS inhibition now gives a backbone active enough for a stromal partner to matter.","test":"Randomised phase 2 with mandatory paired biopsies or FAP PET, stromal signature as a stratification factor, overall survival as primary endpoint; go or no-go on survival, not response.","maturity":"preclinical-evidence","actor":"research","cost":"large","horizonYears":8},{"id":"idea-tr1-randomised-phase-2-before-phase-3","kind":"idea","name":"Require a randomised phase 2 before any phase 3","aka":[],"tldr":"Phase 3 trials are often launched on a small single-arm response-rate study with no comparison group, and most then fail. Requiring a randomised phase 2 with a concurrent control first, with exceptions only for large effects in refractory settings, would filter out weak drugs earlier.","summary":"Sponsors and regulators adopt an expectation that phase 3 in a new indication is preceded by a randomised phase 2 (or the phase 2 portion of a seamless design) with a concurrent control, rather than a single-arm response-rate study. Exceptions for very large single-arm effects in refractory settings.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Trial design, endpoints and cost): Davis et al., Availability of evidence of benefits on survival and quality of life of cancer drugs approved by EMA 2009-13 (BMJ 2017)","url":"https://doi.org/10.1136/bmj.j4530"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["orr","pfs"],"trials":[],"people":[],"bottlenecks":["b-trial-design","b-negative-results"],"keyPapers":["paper-davis-bmj"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Programmes with a randomised phase 2 will have a phase 3 success rate at least 15 percentage points higher than programmes proceeding from single-arm phase 2, and overall development cost per approval will fall despite the added step.","rationale":"Response rates in single-arm studies are poor predictors of survival benefit, and phase 3 oncology failure rates are among the highest of any therapeutic area. Randomised phase 2 also yields early estimates for planning the phase 3.","test":"Compare phase 3 success rates for programmes with and without randomised phase 2 across a decade of registry data, adjusting for indication and mechanism.","maturity":"early-clinical","actor":"industry","cost":"medium","horizonYears":3},{"id":"idea-bio2-brain-exposure-disclosure","kind":"idea","name":"Require every oncology candidate to publish how much reaches the brain","aka":[],"tldr":"Whether a drug gets into the brain is measured early in development but rarely published. Making that number public would show which existing drugs could treat brain disease.","summary":"Unbound brain-to-plasma partition coefficients are routinely generated in preclinical development and almost never disclosed, so clinicians and academic groups cannot tell which approved drugs are worth testing in central nervous system disease. A disclosure requirement at investigational new drug or marketing authorisation stage, or a voluntary public registry, would create a searchable resource at near-zero cost.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The brain: barrier and sanctuary): Stupp et al., Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma (NEJM 2005)","url":"https://doi.org/10.1056/NEJMoa043330"}],"tags":[],"related":["fda-approvals","drugbank-chembl","clinicaltrials-gov"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["blood-brain-barrier"],"trials":[],"people":[],"bottlenecks":["b-brain-delivery","b-negative-results","b-knowledge-diffusion"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A public brain exposure registry identifies at least 20 approved oncology drugs with meaningful brain penetration that are not currently used for central nervous system disease, at least five of which merit trials.","rationale":"Similar mandated disclosures, such as trial registration and results reporting, changed behaviour quickly once required. The data already exist inside companies, so the marginal cost of publication is trivial relative to the value of knowing.","test":"Ask ten companies to disclose historical brain exposure data for approved oncology drugs voluntarily; publish the registry and measure how many new central nervous system trials cite it within two years.","maturity":"speculative","actor":"policy","cost":"small","horizonYears":3},{"id":"idea-reg-evidence-gate-before-repurposing-phase3","kind":"idea","name":"Require genetic and target-trial evidence before funding any repurposing phase 3","aka":[],"tldr":"The big metformin cancer trial failed after years and millions, despite strong observational hints. Cheaper checks on causality should be passed before funding the next one.","summary":"MA.32 (metformin in breast cancer) was negative despite extensive observational support that was later attributed to immortal-time and confounding biases. Mendelian randomisation using drug-target genetic proxies, target trial emulation with active-comparator new-user designs in large health records, and pre-registered replication across independent databases can test causal plausibility for a fraction of a trial's cost. The proposal is a funding rule: repurposing phase 3 trials receive public funding only after a standardised evidence gate (genetic support where a proxy exists, at least two concordant target trial emulations, and a plausible dose-response) has been passed and published.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (No incentive to repurpose cheap drugs): Pantziarka et al., The Repurposing Drugs in Oncology (ReDO) Project (ecancer 2014)","url":"https://doi.org/10.3332/ecancer.2014.442"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["real-world-evidence"],"trials":[],"people":[],"bottlenecks":["b-generic-repurposing","b-real-world-evidence"],"keyPapers":["paper-pantziarka-ecancermedicalscience"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Trials passing the gate have a positive-result rate at least twice that of historical repurposing phase 3 trials, and the gate rejects most candidates whose observational support is driven by bias.","rationale":"Drugs with genetic support for their target succeed in development at roughly double the rate; the same logic should apply to repurposing, and target trial emulation can now be run in weeks on national data.","test":"Retrospectively apply the gate to the ten completed oncology repurposing phase 3 trials and check whether it would have predicted their outcomes; then apply prospectively to the next funding round.","maturity":"early-clinical","actor":"research","cost":"small","horizonYears":2},{"id":"idea-fund-head-to-head-mandate","kind":"idea","name":"Require head-to-head trials against the best in class for later entrants","aka":[],"tldr":"Once two drugs of a kind exist, a third should have to prove itself against the best of them, not against an outdated comparison, so patients and payers learn which is actually better.","summary":"Regulators (or payers, through reimbursement rules) require that registration trials for the third and later entrants in an established mechanistic class use the best available in-class agent as the active comparator, or at minimum include a randomised head-to-head arm. Exceptions apply where the new agent addresses a population the incumbents do not. This makes me-too development more expensive and more informative at once: it either yields comparative evidence patients need or diverts capital to novel mechanisms.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Incentives reward me-too drugs and marginal gains): Upadhaya et al., PD1/PDL1 inhibitor clinical trial landscape (Nat Rev Drug Discov 2022)","url":"https://doi.org/10.1038/d41573-022-00030-4"}],"tags":[],"related":["idea-fund-benefit-indexed-exclusivity"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":["pembrolizumab","nivolumab","sacituzumab-govitecan","datopotamab-deruxtecan"],"companies":[],"institutions":[],"pathways":[],"terms":["standard-of-care"],"trials":[],"people":[],"bottlenecks":["b-incentive-misalignment","b-trial-design"],"keyPapers":["paper-upadhaya-nat-rev-drug-discov"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A head-to-head requirement reduces late-in-class registration filings by at least a quarter within five years and produces comparative effectiveness evidence for the majority of remaining in-class approvals, where today almost none exists.","rationale":"The EU and payers such as Germany's G-BA already prefer active comparators; the WHO and IQWiG have argued that placebo- or obsolete-comparator trials waste patients. Comparative trials among PD-1 antibodies and among TROP2 ADCs are essentially absent despite dozens of products.","test":"Implement through a payer coalition's reimbursement criteria (faster than legislation) and count filings and comparator choices in oncology over three years against a pre-period.","maturity":"speculative","actor":"regulator","cost":"small","horizonYears":5},{"id":"idea-acc-post-approval-evidence-over-75","kind":"idea","name":"Require post-approval evidence in patients over 75 and update labels accordingly","aka":[],"tldr":"New cancer drugs are approved on trials of younger, fitter patients, then given mostly to older ones. Regulators should require real-world safety and benefit data in the over-75s and put it on the label.","summary":"The median age of trial participants is often a decade below that of patients treated in practice, and older patients experience more toxicity and discontinuation. Regulators could require, as a condition of approval, a post-marketing registry or pragmatic study in patients over 75 with reporting within three years, and mandate label updates summarising the findings. This would create the evidence that geriatric oncology currently lacks.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Older and multimorbid patients are excluded and undertreated): Mohile et al., Evaluation of geriatric assessment and management on toxic effects of cancer treatment (GAP70+, Lancet 2021)","url":"https://doi.org/10.1016/S0140-6736(21)01789-X"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["real-world-evidence"],"trials":[],"people":[],"bottlenecks":["b-aging-comorbidity","b-real-world-evidence","b-regulatory-fragmentation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Drugs with mandated post-approval studies in the over-75s will have label-specific dosing or safety information for older patients within four years, and prescribing patterns will change measurably in response.","rationale":"Paediatric investigation requirements created an evidence base for children within a decade; the same lever applied to older adults, the majority of patients, would do more.","test":"Pilot the requirement for a set of new approvals and compare completion of studies, label updates, and post-marketing safety signals with historical controls.","maturity":"speculative","actor":"regulator","cost":"medium","horizonYears":4},{"id":"idea-data-ai-screening-endpoints","kind":"idea","name":"Require stage-shift or interval-cancer endpoints for AI in cancer screening","aka":[],"tldr":"AI for screening should be judged on whether it finds dangerous cancers earlier and misses fewer, not just on whether it agrees with radiologists on old images.","summary":"AI in mammography, lung CT and colonoscopy is evaluated on retrospective detection metrics that reward finding more lesions regardless of clinical significance, which risks overdiagnosis. The proposal requires, for adoption in organised screening programmes, evidence on interval cancer rates, stage distribution of detected cancers and recall rates from prospective studies (randomised or well-designed stepped implementations), with post-implementation monitoring of the same endpoints via registry linkage.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (AI that is built but not validated or deployed): Wu et al., How medical AI devices are evaluated: limitations and recommendations from an analysis of FDA approvals (Nature Medicine 2021)","url":"https://doi.org/10.1038/s41591-021-01312-x"}],"tags":[],"related":[],"cancers":[],"sections":["ai-computation","early-detection"],"technologies":["radiology-ai-screening","mammography","low-dose-ct-screening"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["stage-shift"],"trials":[],"people":[],"bottlenecks":["b-ai-validation","b-overdiagnosis","b-early-detection"],"keyPapers":["paper-wu-nat-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Judged on interval cancers and stage shift, some AI tools with strong retrospective performance will show no benefit or increased overdiagnosis, while others will reduce interval cancers, and the endpoint requirement will steer development toward the latter.","rationale":"Screening's history (PSA, thyroid ultrasound) shows that detecting more is not the same as helping; MASAI and similar trials show the correct endpoints are measurable within a programme.","test":"Adopt the endpoint requirement in one national screening programme; evaluate two AI tools via stepped implementation with registry-linked interval cancer follow-up over three years.","maturity":"early-clinical","actor":"regulator","cost":"medium","horizonYears":4},{"id":"idea-tr2-failed-trial-biobank","kind":"idea","name":"Rescue the biological samples from failed trials for biomarker research","aka":[],"tldr":"Trials that fail still collected thousands of blood and tissue samples. Instead of being destroyed, they should be pooled so scientists can learn who might have benefited.","summary":"Negative trials are often the most informative for biomarker discovery: a subgroup may have responded. Samples from discontinued programmes are usually destroyed or locked. A biobank with pre-negotiated transfer terms, linked de-identified clinical data, and an access committee would allow prospective-retrospective biomarker studies and could resurrect drugs for a biomarker-defined population.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Failures are hidden): Anderson et al., Compliance with results reporting at ClinicalTrials.gov (NEJM 2015)","url":"https://doi.org/10.1056/NEJMsa1409364"}],"tags":[],"related":["idea-tr2-prospective-retrospective-path","idea-tr2-shelved-asset-commons"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-negative-results","b-biomarker-validation"],"keyPapers":["paper-anderson-n-engl-j-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"At least two drugs from failed trials in the biobank will produce a validated predictive biomarker leading to a new enrichment trial within five years.","rationale":"Cetuximab in KRAS wild-type colorectal cancer and gefitinib in EGFR-mutant lung cancer were rescued retrospectively from broadly negative or marginal populations. Systematising sample rescue would make such rescues routine.","test":"Secure samples from five recently failed phase 3 oncology trials; fund two biomarker discovery studies; report time to access and findings.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":3},{"id":"idea-reg-weight-based-io-dosing-label","kind":"idea","name":"Restore weight-based dosing and vial sharing for immunotherapy in the label","aka":[],"tldr":"Immunotherapy is given as one flat dose regardless of body size, which means smaller patients get more than they need. Dosing by weight would save a fifth of the drug at no cost to patients.","summary":"Pembrolizumab and nivolumab were developed with weight-based dosing but labelled at flat doses (200 mg, 240 or 480 mg) that exceed the weight-based equivalent for most patients; pharmacokinetic modelling and several observational studies suggest no loss of efficacy from weight-based or capped dosing, and Dutch and other groups estimate savings of 20-30%. The proposal is a regulator-endorsed label update permitting weight-based dosing with dose banding and multi-dose vial sharing, supported by a pragmatic non-inferiority trial where regulators require one.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Prices and value): Prasad, De Jesús & Mailankody, The high price of anticancer drugs: origins, implications, barriers, solutions (Nat Rev Clin Oncol 2017)","url":"https://doi.org/10.1038/nrclinonc.2017.31"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":[],"drugs":["pembrolizumab","nivolumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-drug-pricing","b-dose-optimisation"],"keyPapers":["paper-checkmate-017-nejm-2015","paper-keynote-189-nejm-2018","paper-keynote-564-nejm-2021","paper-prasad-nat-rev-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Weight-based, banded dosing reduces checkpoint inhibitor drug spend per patient by at least 20% with overall survival non-inferior to flat dosing (hazard ratio upper bound below 1.1).","rationale":"Exposure-response for PD-1 antibodies is flat across the approved range, so the flat doses were chosen for convenience and, arguably, revenue; the drug is the same either way.","test":"Pragmatic registry-based randomised trial in one health system comparing weight-based banded dosing with flat dosing across indications, with survival and cost endpoints; petition regulators for label change on the result.","maturity":"early-clinical","actor":"clinic","cost":"medium","horizonYears":3},{"id":"idea-acc-retention-packages-oncology","kind":"idea","name":"Retention packages so trained oncology staff stay: bonds, top-ups, working equipment","aka":[],"tldr":"Radiation oncologists and physicists from poorer countries who train abroad commonly emigrate, and money alone does not keep them. A package combining a return-of-service bond, salary top-ups, a guarantee of working equipment, academic links and a predictable career path, co-funded by government and donors, should be trialled with five-year retention measured.","summary":"Training a radiation oncologist or physicist abroad and losing them to emigration is a common outcome. The evidence from other specialties suggests that money alone does not retain staff; working equipment, professional development, academic links, and predictable career paths matter as much. A retention package co-funded by government and donors, tied to training scholarships, with a return-of-service bond and a functioning-equipment guarantee, could be trialled and its five-year retention measured.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Not enough oncologists, nurses, pathologists, physicists): Yang et al., Projected supply of and demand for oncologists and radiation oncologists through 2025 (JOP 2014)","url":"https://doi.org/10.1200/JOP.2013.001319"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-workforce","b-global-access"],"keyPapers":["paper-yang-j-oncol-pract"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Trainees under a combined retention package will show at least 80% in-country retention at five years, compared with substantially lower historical rates for scholarship recipients without such packages.","rationale":"Return-of-service schemes work when the returning post is credible; combining them with equipment and academic support addresses the reasons people leave.","test":"Follow a prospective cohort of 200 scholarship trainees across several countries with package versus standard scholarship, tracking retention, productivity, and job satisfaction.","maturity":"speculative","actor":"policy","cost":"medium","horizonYears":5},{"id":"idea-tr1-model-based-dose-finding-with-late-toxicity","kind":"idea","name":"Retire the 3+3: model-based dose finding that counts late and chronic side effects","aka":[],"tldr":"The traditional way of finding a dose looks only at severe side effects in the first month. Modern statistical designs can use all patients' data and count the grumbling, long-lasting problems that make people quit months later.","summary":"Phase 1 designs (BOIN, CRM, TITE variants) that incorporate late-onset toxicity, cumulative low-grade toxicity over multiple cycles, patient-reported tolerability and pharmacokinetics into dose selection, with a target of the 'optimal biological dose' rather than the MTD, and with backfill cohorts at lower doses. Regulators expect a model-based design; the 3+3 becomes the exception requiring justification.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Wrong doses): FDA Oncology Center of Excellence, Project Optimus","url":"https://www.fda.gov/about-fda/oncology-center-excellence/project-optimus"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["kinase-inhibitors","adc","checkpoint-inhibitor"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["ruth-plummer"],"bottlenecks":["b-dose-optimisation","b-trial-design"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Model-based designs incorporating late toxicity will recommend lower doses than 3+3 for the same agents in a substantial fraction of cases, and those doses will show lower real-world discontinuation.","rationale":"For chronic oral therapies and immunotherapies, the toxicities that matter appear after cycle 1 and are often grade 2 but persistent; 3+3 is statistically inefficient and structurally blind to them.","test":"Re-analyse completed phase 1 datasets under TITE-BOIN with cumulative toxicity and compare recommended doses to the original; prospectively adopt in a sponsor's early-phase portfolio and track later dose changes.","maturity":"early-clinical","actor":"industry","cost":"small","horizonYears":2},{"id":"idea-bio2-metastasis-funding-floor","kind":"idea","name":"Ring-fence a fifth of national cancer research money for metastasis","aka":[],"tldr":"Spread causes around nine in ten cancer deaths but receives a small slice of research funding. A funding floor would change what gets studied.","summary":"Portfolio analyses have repeatedly put metastasis research at roughly 5-10% of cancer research spend. A committed floor, with a transparent classification method, an annual public report and a dedicated review panel that understands metastasis models, is a pure policy lever with no scientific risk, only allocation risk.","asOf":"2026-09-08","links":[{"label":"MetaVivor research funding","url":"https://www.metavivor.org"}],"tags":[],"related":["globocan"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["nci","cruk"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-metastasis-biology","b-funding-allocation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A ring-fenced metastasis programme with its own review panel doubles the number of funded metastasis-specific projects within three years and measurably increases metastasis-focused clinical trials within eight.","rationale":"Dedicated funding streams reliably grow fields: the same mechanism built radiopharmaceuticals, immunotherapy and paediatric oncology networks. Metastasis loses in general competition because its models are slower and its endpoints harder, which is a review-dynamics problem rather than a merit problem.","test":"One funder pilots a ring-fenced call with pre-registered classification of awards, then compares downstream publications, trials and career retention against matched general-competition awards over five years.","maturity":"speculative","actor":"policy","cost":"small","horizonYears":8},{"id":"idea-acc-risk-stratified-follow-up","kind":"idea","name":"Risk-stratified follow-up: low-risk survivors to primary care with fast re-entry","aka":[],"tldr":"Not every survivor needs to see an oncologist every six months for years. Sort people by recurrence risk, send low-risk survivors back to their family doctor with a clear plan, and guarantee rapid return if something changes.","summary":"Hospital-based follow-up for all survivors consumes specialist capacity without evidence of survival benefit for most low-risk patients. Risk-stratified models (as in England's personalised stratified follow-up) move low-risk patients to supported self-management and primary care, with remote surveillance tests and an open re-access route, reserving specialist follow-up for high-risk patients. Randomised evidence shows equivalence for recurrence detection in breast and colorectal cancer.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Survivorship and late effects are neglected): NCI Office of Cancer Survivorship statistics","url":"https://cancercontrol.cancer.gov/ocs/statistics"}],"tags":[],"related":["idea-acc-nurse-led-follow-up-clinics"],"cancers":["breast-hr-positive","colorectal","prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-workforce"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Risk-stratified follow-up will release at least a quarter of oncology follow-up capacity and will not worsen stage at recurrence or survivor-reported unmet needs.","rationale":"Recurrences are mostly detected by symptoms between visits, not at scheduled visits; the visits serve reassurance that can be delivered differently.","test":"A regional implementation with capacity released, stage at recurrence, time from symptom to re-access, and patient-reported outcomes as endpoints.","maturity":"being-tested-at-scale","actor":"policy","cost":"small","horizonYears":2},{"id":"idea-moon-survivor-lifelong-care-model","kind":"idea","name":"Risk-stratified lifelong care for tens of millions of survivors, automated and shared with primary care","aka":[],"tldr":"Cancer survivors are a huge and growing population with specific long-term risks. Give each a plan matched to their risk, run automatically and shared with their family doctor.","summary":"Survivors face recurrence, second cancers, cardiovascular and endocrine late effects, and psychosocial and financial harm, but follow-up is either oncologist-heavy and unsustainable or absent. The proposal is a national survivorship model: an automated, treatment-specific survivorship care plan generated from the record at end of treatment, risk-stratified pathways (self-managed, primary care-led, shared care, specialist), scheduled surveillance triggered by the record, patient-reported outcome check-ins, and re-entry routes to oncology, with primary care paid for its role.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Survivorship and late effects are neglected): NCI Office of Cancer Survivorship statistics","url":"https://cancercontrol.cancer.gov/ocs/statistics"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["cardio-oncology"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-care-fragmentation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"The model maintains or improves guideline-concordant surveillance and late-effect detection while reducing oncology follow-up visits by half and improving survivor-reported unmet needs.","rationale":"Stratified follow-up trials in breast and colorectal cancer show primary care-led or patient-initiated follow-up is safe for low-risk survivors; automation and payment make it scalable.","test":"Regional implementation trial comparing the model with standard follow-up on surveillance completion, late-effect detection, visits and patient-reported outcomes over five years.","maturity":"early-clinical","actor":"policy","cost":"medium","horizonYears":4},{"id":"idea-gbc-risk-targeted-ultrasound-in-high-incidence-regions","kind":"idea","name":"Risk-targeted ultrasound screening in high-incidence regions, tested against usual care","aka":[],"tldr":"In parts of Chile and northern India gallbladder cancer is common enough that a cheap ultrasound programme aimed at the highest-risk people might catch it while surgery can still cure it. Nobody has run the trial.","summary":"Sixty percent of Tata Memorial's 1,950 gallbladder cancer patients arrived with metastases and only 16 percent could be treated for cure; median survival was 58.2 months for early-stage against 4.2 months for metastatic disease. Risk is concentrated by geography (the Gangetic belt; southern Chile), ancestry (Mapuche), sex, gallstones and typhoid carriage, which makes a targeted rather than population programme plausible. Ultrasound is cheap and available. The risks are overdiagnosis of polyps and over-treatment of stones, which the Kaiser Permanente cohort shows are real in low-incidence settings; a high-incidence setting changes the arithmetic and only a randomised or cluster trial can show whether deaths fall.","asOf":"2026-09-24","links":[{"label":"Patkar et al.: Tata Memorial gallbladder cancer registry, 60 percent metastatic at presentation (Cancer Epidemiol 2025)","url":"https://europepmc.org/article/MED/41237686"},{"label":"Dutta et al.: epidemiology of gallbladder cancer in India (Chin Clin Oncol 2019)","url":"https://europepmc.org/article/MED/31484488"}],"tags":["gallbladder-evidence"],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":["ultrasound"],"targets":[],"drugs":[],"companies":[],"institutions":["tata-memorial"],"pathways":[],"terms":["screening","overdiagnosis","gallbladder-polyp","prophylactic-cholecystectomy"],"trials":[],"people":[],"bottlenecks":["b-early-detection","b-global-access","b-overdiagnosis"],"keyPapers":["paper-patkar-tata-memorial-gallbladder-cancer-registry-cancer-epidemiol-2025","paper-dutta-gallbladder-cancer-epidemiology-india-chin-clin-oncol-2019","paper-szpakowski-gallbladder-polyps-20-year-cohort-jama-netw-open-2020","paper-roa-gallbladder-cancer-primer-nat-rev-dis-primers-2022"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"In districts with age-standardised gallbladder cancer incidence above 10 per 100,000, a risk-scored ultrasound screening programme for women aged 40 to 65 with gallstones or other risk factors will shift stage at diagnosis and reduce gallbladder cancer mortality by 20 percent within ten years.","rationale":"Stage at diagnosis is the dominant determinant of survival; incidence in the target populations is high enough for a positive predictive value that low-incidence settings cannot reach.","test":"Cluster-randomised trial by district in Bihar or Uttar Pradesh and southern Chile, with usual care control, primary endpoint gallbladder cancer mortality at ten years, secondary endpoints stage distribution, cholecystectomy rate and overdiagnosis.","maturity":"speculative","actor":"policy","cost":"medium","horizonYears":10},{"id":"idea-bio2-robotic-convection-delivery","kind":"idea","name":"Robot-placed catheters and live imaging for drug infusion into brain tumours","aka":[],"tldr":"Pumping drugs slowly through fine tubes into a brain tumour can bypass the barrier, but the fluid often leaks away. Robotic placement and live scans would show where it actually goes.","summary":"Convection-enhanced delivery has repeatedly failed in trials, and post-hoc analyses attribute much of the failure to catheter placement and unmonitored backflow rather than to the drug. Robotic stereotactic placement, co-infused imaging tracers and intraoperative MRI make distribution measurable, and chronic implanted port systems permit repeat infusions on an outpatient basis.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The brain: barrier and sanctuary): Stupp et al., Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma (NEJM 2005)","url":"https://doi.org/10.1056/NEJMoa043330"}],"tags":[],"related":[],"cancers":["glioblastoma"],"sections":[],"technologies":["robotic-surgery","mri","litt"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["blood-brain-barrier"],"trials":[],"people":["michael-weller","roger-stupp"],"bottlenecks":["b-brain-delivery","b-negative-results","b-surgery-radiation-innovation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Distribution-verified convection delivery achieves target coverage of over 80% of the intended volume in most patients, and coverage correlates with local control, which would show past failures were delivery failures.","rationale":"No convection trial has reported per-patient coverage as a primary endpoint, so the field has never separated drug failure from delivery failure. Every other interventional field improved once delivery was imaged, as with catheter ablation and endovascular therapy.","test":"A device-focused study with co-infused tracer and MRI quantification of coverage for each infusion, reporting the distribution of coverage before any efficacy claim.","maturity":"early-clinical","actor":"engineering","cost":"medium","horizonYears":6},{"id":"idea-prev-mammography-ai-stepped-wedge","kind":"idea","name":"Roll out AI-supported mammography nationally as a stepped-wedge trial","aka":[],"tldr":"Sweden's MASAI trial showed AI can safely replace one of two radiologists. Rolling it out region by region in a randomised order would prove it works at national scale and that interval cancers do not rise.","summary":"MASAI (Lund) demonstrated a 44% workload reduction and higher cancer detection with AI-supported reading. Rather than piecemeal adoption, propose national programmes adopt in a randomised stepped-wedge order so every region serves as its own control, with interval cancer rate and recall rate as co-primary endpoints.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The hardest cancers are found late): Crosby et al., Early detection of cancer (Science 2022)","url":"https://doi.org/10.1126/science.aay9040"}],"tags":[],"related":[],"cancers":["breast-hr-positive"],"sections":["early-detection","imaging"],"technologies":["mammography","radiology-ai-screening"],"targets":[],"drugs":[],"companies":["lunit"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-early-detection","b-workforce"],"keyPapers":["paper-crosby-science"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"National AI-supported reading reduces radiologist reading load by at least 40% with no increase in interval cancers and no increase in DCIS-only detection.","rationale":"Stepped-wedge gives regulator-grade evidence at the cost of an implementation programme, and detects harms (recall, DCIS inflation) that single-centre trials cannot.","test":"Run a three-year stepped-wedge across about ten regions of a national programme with a pre-registered analysis.","maturity":"being-tested-at-scale","actor":"policy","cost":"medium","horizonYears":4},{"id":"idea-bio1-alternating-schedules","kind":"idea","name":"Rotate between drugs on a fixed schedule instead of waiting for failure","aka":[],"tldr":"Hospitals rotate antibiotics to stop bacteria adapting. Cycling between two cancer drugs on a set schedule, rather than using one until it fails, might work the same way.","summary":"Antibiotic cycling and mixing are used to manage resistance in intensive care, with mathematical models predicting when each is superior. In oncology, drugs are almost always given until failure. Where two agents with non-overlapping resistance mechanisms and tolerable toxicity exist, scheduled rotation before resistance is established could keep both populations suppressed. Modelling should precede the trial to choose cycle length.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Acquired resistance to every therapy): Soria et al., Osimertinib in untreated EGFR-mutated NSCLC (FLAURA, NEJM 2018)","url":"https://doi.org/10.1056/NEJMoa1713137"}],"tags":[],"related":["prostate-roadmap","idea-prostate-bipolar-androgen-therapy-phase-3-on-pfs2","idea-prostate-randomise-the-sequence-not-only-the-drugs"],"cancers":["breast-hr-positive","prostate"],"sections":[],"technologies":["endocrine-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["bipolar-androgen-therapy","intermittent-androgen-deprivation"],"trials":[],"people":[],"bottlenecks":["b-resistance","b-combination-space"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Scheduled rotation between two non-cross-resistant agents extends time to progression compared with sequential use of the same agents, with equivalent cumulative toxicity.","rationale":"Rotation denies any single clone a sustained selective advantage; the approach requires only existing drugs and a schedule change, making it unusually cheap to test.","test":"Model-informed randomised phase 2 in a setting with two well-tolerated non-cross-resistant options (for example endocrine agents or maintenance regimens), comparing rotation with sequence.","maturity":"speculative","actor":"research","cost":"medium","horizonYears":5},{"id":"idea-acc-remote-planning-hubs","kind":"idea","name":"Round-the-clock remote treatment-planning hubs for clinics without physicists","aka":[],"tldr":"Hospitals without enough physicists could upload scans to a shared planning centre, where AI drafts the treatment plan and remote experts finish and check it within a day.","summary":"Radiotherapy planning (contouring organs and target, optimising beams, quality assurance) is the scarcest skill in radiotherapy centres that lack physicists and dosimetrists. A cloud planning hub combining AI auto-segmentation with a pooled roster of dosimetrists and physicists in higher-capacity centres would turn a two-week wait into a 24-hour service. Commercial contouring software already exists; the missing piece is the organisational and regulatory model that lets a physicist in one country sign off a plan for another.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Most of the world has almost no cancer care): WHO fact sheet, Cancer","url":"https://www.who.int/news-room/fact-sheets/detail/cancer"}],"tags":[],"related":[],"cancers":[],"sections":["radiation","ai-computation"],"technologies":["imrt-igrt"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-global-access","b-workforce"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A regional planning hub will reduce median simulation-to-first-treatment time from more than 14 days to under 5 days in participating centres, with plan-quality audit scores at least equal to locally produced plans.","rationale":"Teleradiology proved that image interpretation can be pooled across borders with quality maintained; planning is a similar knowledge-work bottleneck with a structured output that is easy to audit.","test":"A twelve-month pilot in five LMIC centres with blinded plan-quality review by an independent physics group, time-to-treatment and re-plan rates as endpoints, and a costed model of hub economics.","maturity":"early-clinical","actor":"engineering","cost":"medium","horizonYears":3},{"id":"idea-data-ai-decommissioning-rules","kind":"idea","name":"Rules for retiring cancer AI when performance drops or the standard of care moves","aka":[],"tldr":"Just as drugs are withdrawn when they prove unsafe, AI tools should have clear triggers for being switched off, and someone responsible for pulling the switch.","summary":"No framework exists for taking a deployed model out of service: models trained on outdated staging or treatment eras continue to run. The proposal defines decommissioning triggers (performance below threshold on monitoring, guideline change affecting the task, vendor withdrawal, unaddressed red-team findings), assigns responsibility (site clinical AI officer, vendor, regulator), and requires notification of affected patients where results may have been wrong, mirroring device recall processes.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (AI that is built but not validated or deployed): Wu et al., How medical AI devices are evaluated: limitations and recommendations from an analysis of FDA approvals (Nature Medicine 2021)","url":"https://doi.org/10.1038/s41591-021-01312-x"}],"tags":[],"related":["idea-data-drift-monitoring-standard","idea-data-clinical-ai-model-registry"],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-ai-validation"],"keyPapers":["paper-wu-nat-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Explicit decommissioning rules will lead to retirement of a measurable share of currently deployed cancer AI tools that are obsolete or under-performing, and will shorten the time between trigger and action.","rationale":"Software in other safety-critical domains has defined end-of-life processes; healthcare AI has accumulated a decade of deployments with no retirement mechanism.","test":"Apply the rules to the AI inventory of one health system; count tools meeting decommissioning triggers; measure time to action.","maturity":"speculative","actor":"clinic","cost":"small","horizonYears":1},{"id":"idea-tr2-automated-stats-check","kind":"idea","name":"Run automated statistics and image checks on every cancer manuscript before review","aka":[],"tldr":"Software can already spot impossible statistics, mismatched p-values and duplicated images in a paper. Journals should run these checks on every submission, as spell-check runs on every document.","summary":"Tools such as statcheck (recomputing p-values from reported test statistics), GRIM and SPRITE (checking whether means are possible given sample sizes) and image-duplication detectors identify errors and manipulation at scale. Some journals run image checks; almost none run statistical checks routinely. Integrating a pipeline at submission, with results shown to authors and reviewers, would catch a substantial fraction of errors before publication and deter fabrication.","asOf":"2026-09-08","links":[{"label":"statcheck","url":"https://github.com/MicheleNuijten/statcheck"}],"tags":[],"related":["idea-tr2-outcome-switching-monitor","idea-tr2-raw-image-deposit"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-reproducibility"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Routine checks flag actionable issues in at least 10% of oncology submissions, and journals using them see a lower subsequent correction and retraction rate than matched journals without them.","rationale":"statcheck found inconsistent p-values in about half of psychology papers, with a meaningful share changing significance; image duplication has been documented in about 4% of biomedical papers.","test":"Deploy the pipeline at two oncology journals for a year; report flag rates, author responses and downstream correction rates.","maturity":"early-clinical","actor":"engineering","cost":"small","horizonYears":1},{"id":"idea-lung-small-cell-platform-with-shared-controls-and-subtypes","kind":"idea","name":"Run small-cell lung cancer as one platform with shared controls and subtype stratification","aka":[],"tldr":"Small-cell lung cancer has had two real advances in twenty-five years. It is probably four diseases being tested as one, in separate small trials that each need their own control group.","summary":"Rudin and eighteen colleagues proposed that small-cell lung cancer comprises subtypes defined by ASCL1, NeuroD1, YAP1 and POU2F3 expression, with different therapeutic vulnerabilities. George's genomes explain why conventional targeting failed: the disease is defined by biallelic loss of TP53 and RB1, and losses cannot be inhibited. Progress since has come from elsewhere, from DLL3 as a surface target and from immunotherapy given at lower tumour burden.\n\nThe disease is uncommon enough, and deteriorates fast enough, that individual randomised trials are slow and underpowered, and every one of them spends half its patients on a control arm that is the same in all of them. A platform trial with a shared control, subtype stratification at entry and the ability to drop and add arms is the design the situation calls for, and Lung-MAP has already shown it is operable in squamous non-small-cell disease.","asOf":"2026-09-25","links":[],"tags":["lung-evidence"],"related":["idea-sclc-subtype-directed","trial-modernisation-roadmap","lung-cancer-evidence-roadmap"],"cancers":["lung-cancer","sclc","limited-stage-sclc","extensive-stage-sclc"],"sections":["drug-discovery","immunotherapy"],"technologies":["t-cell-engager","ihc"],"targets":["dll3","tp53","rb1"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["lung-map"],"people":[],"bottlenecks":["b-rare-cancers","b-trial-design","b-undruggable-targets","b-trial-enrolment"],"keyPapers":["paper-rudin-sclc-molecular-subtypes-nat-rev-cancer-2019","paper-george-sclc-genomic-profiles-nature-2015","paper-dellphi-301-nejm-2023","paper-paz-ares-caspian-durvalumab-es-sclc-lancet-2019"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A subtype-stratified platform trial with a shared control arm detects subtype-specific treatment effects in small-cell lung cancer that parallel-group trials of the same total size cannot, and does so fast enough to matter in a disease with a median survival under a year in extensive stage.","rationale":"Shared controls raise the proportion of patients on experimental arms and cut the sample size needed per comparison. Subtype assignment is measurable on diagnostic material by immunohistochemistry or expression profiling. The candidate arms already exist: DLL3-directed engagers in ASCL1-high disease, PARP and ATR inhibitors where replication stress is high, and checkpoint blockade where inflammation is. Lung-MAP established the operational model in the same tumour site.","test":"A platform protocol in extensive-stage small-cell lung cancer with prospective subtype assignment at registration, a standing platinum-etoposide plus checkpoint inhibitor control, and at least three experimental arms with pre-specified subtype hypotheses and futility rules. Success is measured both on arm-level results and on whether subtype prospectively predicts benefit.","maturity":"preclinical-evidence","actor":"research","cost":"large","horizonYears":7},{"id":"idea-pdac-new-onset-diabetes-risk-score-pathway","kind":"idea","name":"Run the ENDPAC score on every new diabetes diagnosis after 50 and scan the high scorers","aka":[],"tldr":"About 1 in 100 people who develop diabetes after 50 has a pancreatic cancer behind it. A score built from weight change, blood sugar change and age, calculable from records already in primary care, picks out a group where the rate is nearer 1 in 30; the proposal is to scan that group rather than wait for symptoms.","summary":"Chari's population cohort found pancreatic cancer in 0.85 percent of 2,122 new diabetics aged 50 or over within three years, an observed-to-expected ratio of 7.94, with 10 of 18 diagnosed within six months of the diabetes. Sharma's ENDPAC model (weight change, glucose change, age at onset) had an area under the curve of 0.87; in validation a score of 3 or more identified 78 percent of cancers at 85 percent specificity, with a prevalence of 3.6 percent among high scorers, and a score of 0 or below in 49 percent of patients marked extremely low risk. The proposal is a pragmatic pathway, not a new test: an automated ENDPAC flag in the primary care record at diabetes diagnosis, contrast CT or MRI for scores of 3 or more, and CA 19-9 with awareness that Lewis-negative patients (Tempero 1987) cannot make it. It is distinct from the existing OnCo idea of a blood-based multi-cancer test in the same population and can precede it, because imaging is available now. The test is a prospective cohort with stage at diagnosis against contemporaneous controls; the Hungarian NODES cohort (2,522 estimated) and the US NOD cohort are the nearest running studies. The UK, where diabetes diagnoses are coded in a single primary care system, is an unusually good place to run it.","asOf":"2026-09-24","links":[{"label":"Sharma et al.: ENDPAC model (Gastroenterology 2018)","url":"https://europepmc.org/article/MED/29775599"},{"label":"Chari et al.: probability of pancreatic cancer following diabetes (Gastroenterology 2005)","url":"https://europepmc.org/article/MED/16083707"},{"label":"ClinicalTrials.gov NCT04164602","url":"https://clinicaltrials.gov/study/NCT04164602"}],"tags":["pancreatic-evidence"],"related":["idea-mced-new-onset-diabetes","early-detection-roadmap"],"cancers":["pancreatic"],"sections":[],"technologies":["ct","mri","pancreatic-surveillance"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["ppv","ca19-9"],"trials":[],"people":[],"bottlenecks":["b-early-detection","b-biomarker-validation"],"keyPapers":["paper-chari-pancreatic-cancer-following-diabetes-gastroenterology-2005","paper-sharma-endpac-model-new-onset-diabetes-gastroenterology-2018","paper-fahrmann-ca19-9-lead-time-gastroenterology-2021","paper-tempero-ca19-9-lewis-antigens-cancer-res-1987"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"An automated ENDPAC score at new diabetes diagnosis after 50, with imaging for scores of 3 or more, detects pancreatic cancer at a resectable stage in a higher proportion than symptomatic presentation and finds one cancer for every 30 to 40 people scanned.","rationale":"The score needs no new assay, the prevalence in high scorers is high enough for a scan to be justified, and 75 percent of cases in the derivation cohort were flagged more than six months before diagnosis.","test":"Prospective pragmatic cohort in a primary care network: ENDPAC computed at diagnosis, imaging for high scorers, three-year cancer ascertainment; primary outcome stage distribution and resection rate versus matched contemporaneous cases; secondary outcomes scans per cancer found and incidental findings.","maturity":"early-clinical","actor":"clinic","cost":"medium","horizonYears":5},{"id":"idea-bio1-co-clinical-avatar-trials","kind":"idea","name":"Run the mouse or organoid trial at the same time as the human trial","aka":[],"tldr":"Instead of testing a drug in lab models first and hoping the results carry over, build the same models from trial participants and run both experiments in parallel to see how well the models predict.","summary":"Co-clinical trials generate patient-derived organoids or xenografts from enrolled participants and treat them with the trial regimen, with model results locked and blinded until the clinical readout. This produces a prospective, unbiased estimate of model predictive value, which the field currently lacks, and gives a resource for studying the responders and non-responders.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Lab models that fail to predict what happens in patients): Wong, Siah & Lo, Estimation of clinical trial success rates (Biostatistics 2019)","url":"https://doi.org/10.1093/biostatistics/kxx069"}],"tags":[],"related":["idea-organoid-guided-adc"],"cancers":[],"sections":[],"technologies":["organoids","pdx-models","functional-drug-testing"],"targets":[],"drugs":[],"companies":["champions-oncology","xilis"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-preclinical-models","b-biomarker-validation"],"keyPapers":["paper-wong-biostatistics"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Blinded, prospectively locked avatar predictions achieve a positive predictive value above 70 percent for clinical response in at least one modality, establishing which model system deserves decision-making weight.","rationale":"Retrospective concordance figures for organoids are encouraging but subject to selection and reporting bias. Only prospective locking measures true predictive value, as was done for imaging biomarkers.","test":"Attach an avatar sub-study to three ongoing phase 2 trials in different tumour types with pre-registered analysis; report predictive values regardless of direction.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":4},{"id":"idea-prev-hpv-same-day-screen-and-treat","kind":"idea","name":"Same-day HPV test and heat treatment of precancer by nurses in low-income settings","aka":[],"tldr":"Where women cannot return for results, test for HPV and treat any precancer the same day with a battery-powered heat probe. This is the fastest route to WHO's cervical elimination target.","summary":"Where women cannot return for results, this idea has nurses test for HPV and treat any precancer the same day with a battery-powered thermal ablation probe, supported by point-of-care HPV testing and digital tracking and financed through Gavi and Global Fund mechanisms. WHO recommends HPV DNA testing as the primary screen and thermal ablation for screen-positive women in screen-and-treat settings, and loss to follow-up is the largest leak in low-income screening, so same-day delivery closes it. The test is a cluster RCT of same-day versus two-visit models in three countries. Being tested at scale, it addresses the bottlenecks Prevention we already have is not deployed and Most of the world has almost no cancer care.","asOf":"2026-09-08","links":[{"label":"WHO cervical cancer elimination initiative","url":"https://www.who.int/initiatives/cervical-cancer-elimination-initiative"}],"tags":[],"related":[],"cancers":["cervical"],"sections":["prevention"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption","b-global-access"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Same-day programmes achieve at least 80% treatment completion of screen-positives (versus under 50% for multi-visit models) and reduce cervical cancer incidence by at least 30% in covered populations within ten years.","rationale":"Loss to follow-up is the largest leak in low-income screening; same-day closes it.","test":"Cluster RCT of same-day versus two-visit models in three countries.","maturity":"being-tested-at-scale","actor":"policy","cost":"large","horizonYears":5},{"id":"idea-fund-national-drug-development-office","kind":"idea","name":"Scale up public drug development that takes academic assets to phase 1","aka":[],"tldr":"The US government already runs a small programme that turns academic cancer discoveries into drugs ready for human trials. Scale it up tenfold and copy it in other countries.","summary":"NCI's Experimental Therapeutics (NExT) programme and the Cancer Research UK Centre for Drug Development show that public bodies can run medicinal chemistry, pharmacology and IND-enabling work on academic targets and then license candidates to companies. Both are small relative to the pipeline of stranded academic discoveries. The proposal is to expand these to tens of concurrent programmes each, prioritising undruggable and neglected targets, with explicit licensing-out at phase 1 or 2 and revenue returning to the programme. Public development is also the natural home for assets with no commercial sponsor (rare cancers, generics, combinations of competitors' drugs).","asOf":"2026-09-08","links":[{"label":"NCI NExT Program","url":"https://next.cancer.gov/"}],"tags":[],"related":["idea-fund-translational-institutes-gmp","idea-fund-nonprofit-pharma"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["nci","cruk","icr-london"],"pathways":[],"terms":[],"trials":[],"people":["paul-workman","chris-lord"],"bottlenecks":["b-translational-valley","b-undruggable-targets"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A tenfold expansion of public drug development capacity brings at least fifteen academically-originated oncology candidates to phase 1 per year within six years and results in at least five licences to industry on terms that recover a meaningful share of costs.","rationale":"NExT has progressed multiple agents to the clinic and licensed several; CRUK's centre has taken dozens of agents into humans and contributed to approved drugs (including through its early support of PARP inhibitor and abiraterone development). The model works at small scale; the question is whether it scales, which the pilot tests.","test":"Fund an expansion tranche of ten new programmes with public milestone reporting and compare progression and licensing rates with the historical programme baseline.","maturity":"early-clinical","actor":"policy","cost":"large","horizonYears":6},{"id":"idea-fund-scoop-protection-policy","kind":"idea","name":"Scoop protection and co-publication norms to reduce academic secrecy","aka":[],"tldr":"Scientists hide results for fear of being beaten to publication. If journals and funders guaranteed that a preprinted finding cannot be scooped, and encouraged rival groups to publish side by side, sharing would become safe.","summary":"Journals in the cancer field adopt explicit scoop-protection policies (a preprint or registered report establishes priority and a competing paper appearing during review does not affect acceptance, as PLOS and eLife have done) and funders count preprints as outputs. Add a co-publication mechanism in which groups working on the same question are matched and encouraged to publish back-to-back with cross-replication, which the field treats as a strength. Secrecy delays diffusion and, by preventing early cross-checking, contributes to irreproducible claims reaching translation.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Secrecy and intellectual property block collaboration): Danchev et al., Evaluation of data sharing after implementation of the ICMJE data sharing statement requirement (JAMA Netw Open 2021)","url":"https://doi.org/10.1001/jamanetworkopen.2020.33972"}],"tags":[],"related":["idea-fund-open-results-bonus","idea-fund-academic-promotion-reform"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-ip-collaboration","b-reproducibility","b-knowledge-diffusion"],"keyPapers":["paper-danchev-jama-netw-open"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"In the two years after major oncology journals adopt scoop protection, the share of cancer biology papers preprinted before submission rises by at least half and surveys show a measurable fall in reported withholding of methods and data before publication.","rationale":"Preprinting rates rose sharply in fields where journals signalled acceptance and protection (genomics, neuroscience); the pandemic showed biomedical researchers will share early when norms permit. Back-to-back publication of independent confirmations is already a respected format in structural biology and genetics.","test":"Track preprint rates and survey-reported withholding in oncology before and after policy adoption by a coalition of journals and funders, compared with a field without the change.","maturity":"speculative","actor":"research","cost":"small","horizonYears":2},{"id":"idea-bio1-model-predictivity-benchmark","kind":"idea","name":"Score every model system on how well it predicted real trial results","aka":[],"tldr":"No one keeps score of which laboratory models actually predicted what happened in patients. A public scoreboard would show which models to trust.","summary":"Protein structure prediction improved rapidly once CASP created a blinded, periodic benchmark. An oncology equivalent would take drugs with known but embargoed clinical outcomes, ask model owners (organoids, PDX, chips, in silico) to submit blinded predictions of response rate or ranking, and publish accuracy by model class. Over time this creates evidence for which systems merit regulatory and investment weight.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Lab models that fail to predict what happens in patients): Wong, Siah & Lo, Estimation of clinical trial success rates (Biostatistics 2019)","url":"https://doi.org/10.1093/biostatistics/kxx069"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["organoids","pdx-models","ai-drug-design"],"targets":[],"drugs":[],"companies":[],"institutions":["broad-institute"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-preclinical-models","b-ai-validation","b-reproducibility"],"keyPapers":["paper-wong-biostatistics"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Blinded benchmarking reveals large and reproducible differences between model classes in predicting clinical response rates, and participation improves accuracy across rounds.","rationale":"Community benchmarks with held-out truth transformed structural biology and machine learning; oncology model validation is currently self-reported and non-comparable.","test":"Run a first round with ten agents whose phase 2 results are complete but unpublished or paywalled, and publish accuracy metrics per submitted model class.","maturity":"speculative","actor":"data","cost":"small","horizonYears":3},{"id":"idea-tr2-model-report-cards","kind":"idea","name":"Score every preclinical model by how often it predicted the clinical result","aka":[],"tldr":"For each type of laboratory model, keep a public record of how often its predictions came true in patients, so that researchers know which models to trust for which question.","summary":"Model predictivity is asserted, not measured. Linking preclinical efficacy claims (from publications and investigational new drug packages) to subsequent clinical outcomes would yield per-model, per-indication predictive values: for instance how often cell-line xenograft regression preceded objective responses in the same indication. Failures are essential to this calculation, which is why they must be recorded.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Failures are hidden): Anderson et al., Compliance with results reporting at ClinicalTrials.gov (NEJM 2015)","url":"https://doi.org/10.1056/NEJMsa1409364"}],"tags":[],"related":["cancer-models","idea-tr2-failure-taxonomy"],"cancers":[],"sections":[],"technologies":["pdx-models","organoids"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-negative-results","b-preclinical-models"],"keyPapers":["paper-anderson-n-engl-j-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Report cards will show at least two-fold differences in positive predictive value between model classes within the same indication, and this information will change model choice in subsequent grant applications.","rationale":"Systematic reviews in stroke and neuroscience showed that animal model results predicted clinical results poorly; oncology has never computed the equivalent at scale despite having the most trials.","test":"Link 300 drug-indication pairs with published preclinical data to trial outcomes; compute predictive values by model class; publish and update annually.","maturity":"speculative","actor":"data","cost":"small","horizonYears":3},{"id":"idea-reg-financial-toxicity-vital-sign","kind":"idea","name":"Screen every cancer patient for financial toxicity as a vital sign, with navigation","aka":[],"tldr":"Cancer costs push patients into debt and make them skip treatment. Asking about money at every visit, and having someone to help, catches this before it does harm.","summary":"Financial toxicity affects a large share of patients even in insured and universal systems and is associated with non-adherence and worse survival. Validated instruments (COST-FACIT) exist, and financial navigation programmes have shown reductions in patient debt and distress in US trials. The proposal is to embed a short financial toxicity screen in routine patient-reported outcome collection at each cycle, with an automatic referral to a financial navigator and a data feed to payers documenting the burden by drug and regimen.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Prices and value): Prasad, De Jesús & Mailankody, The high price of anticancer drugs: origins, implications, barriers, solutions (Nat Rev Clin Oncol 2017)","url":"https://doi.org/10.1038/nrclinonc.2017.31"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-drug-pricing","b-toxicity-qol"],"keyPapers":["paper-prasad-nat-rev-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Routine screening with navigation reduces the proportion of patients reporting severe financial toxicity by a third, reduces treatment non-adherence for oral oncolytics, and generates drug-level financial burden data that payers use in negotiations.","rationale":"Financial toxicity is a recognised adverse effect that is not measured, so it is not managed; the same logic that made pain a vital sign applies, and navigation interventions have randomised evidence of benefit.","test":"Cluster-randomised trial across 20 cancer centres of routine screening plus navigation versus usual care with financial toxicity score, adherence and out-of-pocket cost at 12 months.","maturity":"early-clinical","actor":"clinic","cost":"medium","horizonYears":3},{"id":"idea-acc-financial-toxicity-screening-at-diagnosis","kind":"idea","name":"Screen every patient for financial hardship at diagnosis and connect them to help","aka":[],"tldr":"Cancer often ruins families financially, and money worries make people skip treatment. Ask about finances at the first visit, as routinely as asking about allergies, and route people to assistance.","summary":"Financial toxicity is common, predicts non-adherence and worse outcomes, and is rarely assessed. Validated brief instruments (such as the COST measure) can be added to intake, with positive screens triggering referral to financial navigators, charity programmes, and benefit advice. This is cheap and addresses a cause of care fragmentation and abandonment in every health system, insured or not.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Fragmented care and guideline gaps): Hanna et al., Mortality due to cancer treatment delay: systematic review and meta-analysis (BMJ 2020)","url":"https://doi.org/10.1136/bmj.m4087"}],"tags":[],"related":["idea-acc-funded-navigator-per-diagnosis"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-care-fragmentation","b-patient-voice","b-drug-pricing"],"keyPapers":["paper-hanna-bmj"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Routine financial screening with navigation will reduce treatment non-adherence attributable to cost by at least a third and improve financial-toxicity scores at six months.","rationale":"Screening for distress became standard once it was embedded in intake; financial hardship is more prevalent than clinical distress and has a clearer remedy.","test":"A randomised implementation across ten clinics with adherence, financial-toxicity scores, and use of assistance as endpoints.","maturity":"early-clinical","actor":"clinic","cost":"small","horizonYears":2},{"id":"idea-moon-financial-toxicity-screening","kind":"idea","name":"Screen every patient for financial toxicity at diagnosis and refer like any other symptom","aka":[],"tldr":"Ask about money problems with a short validated questionnaire when treatment starts, and route those at risk to financial navigators before bills cause missed doses.","summary":"Financial toxicity is associated with non-adherence, bankruptcy and worse survival, and is invisible unless asked about. The COST-FACIT instrument is validated and short. The proposal is universal screening at diagnosis and at each treatment change, with automatic referral to financial navigation (benefits, assistance programmes, employment rights, billing review), and inclusion of the score as a routinely collected outcome in registries and trials.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Patients lack understanding, navigation and agency): Basch et al., Overall survival results of a trial assessing patient-reported outcomes for symptom monitoring during routine cancer treatment (JAMA 2017)","url":"https://doi.org/10.1001/jama.2017.7156"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-patient-voice","b-drug-pricing"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Screening plus navigation reduces treatment non-adherence for financial reasons and self-reported financial distress at six months, and cuts uncollectable debt for hospitals.","rationale":"Financial navigation programmes recover assistance funding worth many times their cost; the barrier is identification, not solutions.","test":"Randomised trial of screening-plus-navigation versus usual care in two health systems; primary endpoint COST score at six months, secondary adherence, out-of-pocket spend and debt.","maturity":"early-clinical","actor":"clinic","cost":"small","horizonYears":2},{"id":"idea-cost-financial-toxicity-screening","kind":"idea","name":"Screen every patient for money trouble the way we screen for pain","aka":[],"tldr":"People with cancer are far more likely to go bankrupt than people without, and the ones who do have worse survival; a two-question screen at diagnosis plus a financial navigator catches the problem while it can still be fixed.","summary":"A Washington State study linking cancer registry and court records (Ramsey et al., Health Affairs 2013) found people with cancer were 2.65 times more likely to file for bankruptcy than matched controls. Validated tools (COST, a financial-toxicity score) take two minutes. Financial navigators enrol patients in manufacturer, charity and public programmes, appeal denials and set up payment plans. Making screening a quality measure and navigation a reimbursable service would spread it beyond the large centres that already have it.","asOf":"2026-09-10","links":[{"label":"Ramsey et al., Health Affairs 2013: Washington State cancer patients and bankruptcy","url":"https://doi.org/10.1377/hlthaff.2012.1263"},{"label":"OnCo financial help browser","url":"https://onco-umber.vercel.app/assistance/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["financial-toxicity"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol","b-care-fragmentation","b-patient-voice"],"keyPapers":["paper-ramsey-health-aff-millwood"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Universal financial-toxicity screening with navigation will reduce the share of patients reporting severe financial distress at six months by a third and reduce treatment non-adherence for cost reasons.","rationale":"Every large centre that has published its navigation programme reports millions of dollars of assistance secured per navigator per year; the evidence gap is in smaller and rural practices.","test":"A cluster-randomised trial of screening plus navigation in community practices with distress scores, adherence, assistance secured and bad debt as endpoints.","maturity":"being-tested-at-scale","actor":"clinic","cost":"small","horizonYears":2},{"id":"idea-bio1-glue-degrader-atlas","kind":"idea","name":"Screen glue-like compounds against every cancer cell line and publish it","aka":[],"tldr":"Molecular glue degraders make one protein destroy another, but thalidomide analogues and indisulam were found by luck. A systematic screen of chemical libraries against genetically diverse cancer cell lines, published as an open atlas, would map which of the roughly 600 human E3 ligases can be redirected and against which targets.","summary":"Molecular glue degraders (thalidomide analogues, indisulam) were discovered serendipitously. Modern discovery pairs a chemical library with degradation readouts (global proteomics, reporter panels) across genetically diverse lines, using E3 ligase knockouts to confirm mechanism. A precompetitive atlas of compound-to-degraded-protein pairs would map which of the roughly 600 human E3 ligases can be redirected and against which classes of target.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The undruggable drivers): Dang et al., Drugging the 'undruggable' cancer targets (Nature Reviews Cancer 2017)","url":"https://doi.org/10.1038/nrc.2017.36"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["protac-degrader","proteomics"],"targets":[],"drugs":[],"companies":["monte-rosa","nurix","kymera","c4-therapeutics"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-undruggable-targets","b-ip-collaboration"],"keyPapers":["paper-dang-nat-rev-cancer"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Systematic glue screening at scale identifies degradation of at least 50 proteins with no known small-molecule binding site, including at least five transcription factors of oncological interest.","rationale":"Glue mechanisms do not require a target pocket, so they extend the druggable proteome to interaction surfaces. The technology is now industrialised but siloed inside a handful of companies.","test":"A funded consortium screening 100,000 compounds with proteome-wide degradation readouts across 20 lines; success measured by independently confirmed novel degraded targets released publicly.","maturity":"preclinical-evidence","actor":"philanthropy","cost":"large","horizonYears":5},{"id":"idea-tr1-seamless-2-3-with-prespecified-go","kind":"idea","name":"Seamless phase 2/3 with pre-registered go rules as the default for new agents","aka":[],"tldr":"Instead of stopping after the mid-sized trial, waiting a year, then starting the big one, run them as one study with a clear pre-agreed rule for continuing. This saves a year or more per drug.","summary":"Adaptive seamless designs where the phase 2 portion (dose or population selection) rolls into the phase 3 portion without a pause, with a pre-registered decision rule, an independent committee applying it, and appropriate statistical control of type I error. The idea is to make this the expected design for agents with a plausible registrational path, with regulators offering fast-track review of the adaptation plan.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Trial design, endpoints and cost): Davis et al., Availability of evidence of benefits on survival and quality of life of cancer drugs approved by EMA 2009-13 (BMJ 2017)","url":"https://doi.org/10.1136/bmj.j4530"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["pfs","os"],"trials":[],"people":[],"bottlenecks":["b-trial-design"],"keyPapers":["paper-davis-bmj"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Programmes using seamless 2/3 designs will reach primary phase 3 read-out at least 12 months sooner than matched programmes with separate phases, without a higher rate of failed phase 3s.","rationale":"Operational pauses between phases account for a sizeable share of development time. Seamless designs have supported approvals in several cancers; the remaining barrier is habit and the need for early commitment to the confirmatory endpoint.","test":"Compare development timelines (first-in-human to pivotal read-out) for seamless versus sequential programmes in the same drug class, using registry start and completion dates.","maturity":"being-tested-at-scale","actor":"industry","cost":"large","horizonYears":3},{"id":"idea-bio2-gdf15-stratified-enrolment","kind":"idea","name":"Select cachexia trial patients by the hormone driving their wasting","aka":[],"tldr":"Wasting has several causes. Measuring the specific hormone in each patient's blood would put the right patients into the right trial instead of mixing everyone together.","summary":"Cachexia trials have historically enrolled by weight loss criteria alone, mixing inflammatory, anorexic, hypermetabolic and mechanical causes. Plasma GDF-15, interleukin-6, C-reactive protein and resting energy expenditure define mechanistically distinct groups. Enriching for high GDF-15 in anti-GDF-15 trials, and for high interleukin-6 in anti-inflammatory trials, is straightforward and cheap.","asOf":"2026-09-08","links":[{"label":"GDF15","url":"https://en.wikipedia.org/wiki/GDF15"}],"tags":[],"related":[],"cancers":["pancreatic","nsclc"],"sections":[],"technologies":["proteomics"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-cachexia-supportive","b-biomarker-validation","b-trial-design"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Biomarker-stratified enrolment increases the observed treatment effect size in cachexia trials by at least 50% relative to unselected enrolment, converting historically borderline results into clear ones.","rationale":"Mechanistic stratification rescued many oncology drugs that failed in unselected populations. Cachexia is arguably the least stratified field in oncology despite having measurable, causally relevant plasma markers.","test":"Retrospectively stratify banked samples from completed cachexia trials by GDF-15 and interleukin-6 and test for treatment-by-biomarker interaction; if present, mandate stratification prospectively.","maturity":"speculative","actor":"industry","cost":"small","horizonYears":4},{"id":"idea-crc-mss-immunotherapy-by-biomarker-not-by-line","kind":"idea","name":"Select microsatellite stable patients for immunotherapy by a measured immune biomarker, not by how many treatments they have already failed","aka":[],"tldr":"Ninety-five percent of advanced bowel cancers ignore immunotherapy, and the only real signal so far came in patients without active liver secondaries. Trials keep enrolling by treatment line rather than by immune biology, which guarantees the responders are diluted away.","summary":"Le's original study set the boundary: 40 percent response in mismatch repair-deficient colorectal cancer, 0 of 18 in proficient disease, with 1,782 against 73 somatic mutations per tumour. Botensilimab, an Fc-enhanced anti-CTLA-4 antibody, with balstilimab gave the first credible microsatellite stable signal: 17 percent response and 61 percent disease control in 101 evaluable heavily pre-treated patients, with responses concentrated in those without active liver metastases.\n\nThe field has two measurable handles it does not use for enrolment. Galon's immune contexture showed in 2006 that the type, density and location of T cells in a colorectal tumour predicts outcome better than stage, and the consensus molecular subtypes separate the immune-infiltrated CMS1 and the mesenchymal, TGF-beta-driven CMS4 that excludes T cells. A trial that enrolled by Immunoscore band, CMS class and liver-metastasis status would test the combination in the population where the mechanism predicts it can work, rather than in whoever has exhausted chemotherapy.","asOf":"2026-09-24","links":[{"label":"Bullock et al.: botensilimab plus balstilimab in MSS colorectal cancer (Nat Med 2024)","url":"https://europepmc.org/article/MED/38871975"},{"label":"Le et al.: PD-1 blockade in mismatch-repair deficiency (N Engl J Med 2015)","url":"https://europepmc.org/article/MED/26028255"},{"label":"ClinicalTrials.gov NCT05608044","url":"https://clinicaltrials.gov/study/NCT05608044"}],"tags":["colorectal-evidence"],"related":["colorectal-roadmap","immunotherapy-roadmap","idea-immunotherapy-mss-crc"],"cancers":["colorectal"],"sections":["immunotherapy"],"technologies":["checkpoint-inhibitor"],"targets":["ctla4","pd1","tgf-beta"],"drugs":["botensilimab","balstilimab","nivolumab","ipilimumab","pembrolizumab"],"companies":["agenus"],"institutions":[],"pathways":[],"terms":["msi","cms-subtypes","cold-vs-hot","neoantigen"],"trials":[],"people":[],"bottlenecks":["b-immunotherapy-response","b-tme-immunosuppression","b-biomarker-validation","b-trial-design"],"keyPapers":["paper-bullock-botensilimab-balstilimab-mss-colorectal-nat-med-2024","paper-le-mmr-deficiency-pd1-nejm-2015","paper-galon-immune-contexture-colorectal-science-2006","paper-cms-guinney-nat-med-2015"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"In microsatellite stable metastatic colorectal cancer selected by an immune-exclusion biomarker (high Immunoscore or CMS1-like signature, no active liver metastases), Fc-enhanced CTLA-4 blockade with PD-1 blockade produces an objective response rate above 30 percent and an overall survival benefit against standard refractory-line treatment, where an unselected population shows neither.","rationale":"The one positive signal in this population is already concentrated in a biologically defined subgroup, liver-metastasis-free disease, discovered after the fact; enrolment by line of therapy mixes that subgroup with patients whose tumours have no T cells to release.","test":"A randomised trial stratified prospectively by Immunoscore band, consensus molecular subtype and liver-metastasis status, with overall survival as the primary endpoint in the biomarker-selected stratum and the unselected stratum reported separately; paired biopsies to confirm that responders convert from excluded to inflamed. Kill the hypothesis if response in the selected stratum does not exceed the 17 percent seen unselected.","maturity":"early-clinical","actor":"research","cost":"large","horizonYears":7},{"id":"idea-bio2-til-reactivity-selection","kind":"idea","name":"Select patients for cell therapy by whether their tumour holds reactive T cells","aka":[],"tldr":"Growing a patient's own tumour-fighting cells only works if those cells are there to start with. A test for them would spare futile treatment.","summary":"Tumour-infiltrating lymphocyte therapy is approved in melanoma but works in a minority, and manufacturing takes weeks and costs a great deal. Markers of genuinely tumour-reactive T cells, notably CD39 and CD69 co-expression and CXCL13 expression, distinguish reactive from bystander cells in human tumours. A pre-manufacture biopsy assay could predict product potency and patient benefit.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (No one can predict who responds to immunotherapy): Haslam & Prasad (JAMA Network Open 2019)","url":"https://doi.org/10.1001/jamanetworkopen.2019.2535"}],"tags":[],"related":[],"cancers":["melanoma","nsclc"],"sections":[],"technologies":["til-therapy","single-cell-spatial","flow-cytometry-mrd"],"targets":[],"drugs":["lifileucel"],"companies":["iovance"],"institutions":[],"pathways":[],"terms":["tils"],"trials":[],"people":["john-haanen","ton-schumacher"],"bottlenecks":["b-immunotherapy-response","b-manufacturing-cell-therapy","b-biomarker-validation"],"keyPapers":["paper-haslam-jama-netw-open"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A pre-manufacture reactivity assay predicts objective response to tumour-infiltrating lymphocyte therapy, allowing at least a third of patients unlikely to benefit to avoid a costly and toxic procedure.","rationale":"Bystander T cells dominate many tumours, so total lymphocyte density is a poor proxy for reactivity. Product potency assays are standard in cell therapy manufacture in other diseases, and the markers here are well characterised in human tissue.","test":"Retrospective analysis of banked pre-manufacture biopsies from treated patients for association with response; if positive, use the assay prospectively as an eligibility criterion in one arm of a trial.","maturity":"preclinical-evidence","actor":"industry","cost":"medium","horizonYears":5},{"id":"idea-moon-self-driving-cancer-labs","kind":"idea","name":"Self-driving laboratories that run the cancer biology hypothesis loop autonomously","aka":[],"tldr":"Robotic labs guided by AI that design experiments on tumour models, run them, read the results and design the next ones, around the clock, with every result published openly.","summary":"Autonomous laboratories exist in chemistry and materials science, and cloud labs and robotic organoid culture are emerging in biology. Cancer biology is limited by slow, poorly reproducible manual experimentation. The proposal is a network of self-driving cancer labs: automated organoid and cell line culture, perturbation, imaging and sequencing readouts, active-learning experiment selection against defined questions (resistance mechanisms, combination synergy, dependency mapping), and automatic public deposition of raw data and protocols.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Lab models that fail to predict what happens in patients): Wong, Siah & Lo, Estimation of clinical trial success rates (Biostatistics 2019)","url":"https://doi.org/10.1093/biostatistics/kxx069"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["organoids","crispr-screens","ai-drug-design"],"targets":["kras"],"drugs":[],"companies":["recursion"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-preclinical-models","b-reproducibility","b-translational-valley"],"keyPapers":["paper-wong-biostatistics"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Self-driving labs produce reproducible, reusable results at ten times the throughput and a fraction of the cost per experiment of conventional labs, and their findings translate at a higher rate.","rationale":"Automation removes the variability that undermines reproducibility and lets exploration scale with compute rather than with postdoc hours; open deposition keeps the results usable.","test":"Build one facility focused on resistance to KRAS inhibitors; compare throughput, replication rates and independent validation of findings against a conventional consortium over three years.","maturity":"preclinical-evidence","actor":"engineering","cost":"large","horizonYears":6},{"id":"idea-prev-screening-default-appointments","kind":"idea","name":"Send screening invitations with a pre-booked time, not a request to call","aka":[],"tldr":"Uptake rises when the invitation comes with a booked appointment and text reminders. Make that the default in every screening programme.","summary":"Uptake rises when a screening invitation arrives with a booked appointment and text reminders, so this idea makes that the national standard: every invitation carries a default booked slot with easy rebooking, a GP-endorsed letter and two SMS reminders. Timed appointments, reminders and GP endorsement each raise uptake in randomised trials in UK breast and bowel screening, and behavioural defaults are well understood. The aim is higher uptake overall and especially in the most deprived quintile. The test is programme-level A/B testing at scale, feasible in most call and recall systems. Being tested at scale, it addresses the bottleneck Prevention we already have is not deployed and is linked from the NordICC paper.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Prevention we already have is not deployed): Islami et al., Proportion of cancer attributable to modifiable risk factors (CA 2018)","url":"https://doi.org/10.3322/caac.21440"}],"tags":[],"related":[],"cancers":[],"sections":["prevention","early-detection"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption"],"keyPapers":["paper-islami-ca-cancer-j-clin"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Default slots plus reminders raise uptake by at least 8 percentage points overall and 12 points in the most deprived quintile.","rationale":"Behavioural defaults; multiple randomised trials in UK breast and bowel screening.","test":"Programme-level A/B testing at scale, feasible in most call/recall systems.","maturity":"being-tested-at-scale","actor":"policy","cost":"small","horizonYears":1},{"id":"idea-data-federated-analytics-network","kind":"idea","name":"Send the code to the data: a federated analytics network of cancer centres","aka":[],"tldr":"Hospitals keep their records at home; researchers send in a programme that runs at each hospital and only the summary results come back.","summary":"OHDSI has shown that a common data model (OMOP) plus federated analysis scripts can run identical studies across hundreds of databases without moving patient-level data. Oncology needs the oncology extension of OMOP (episodes, regimens, staging) completed and a standing network of 50 or more cancer centres with a governance committee that approves study packages, not data transfers. Related efforts include the EHDEN network in Europe and PCORnet in the US.","asOf":"2026-09-08","links":[{"label":"OHDSI","url":"https://www.ohdsi.org/"},{"label":"OMOP Oncology working group","url":"https://ohdsi.github.io/OncologyWG/"}],"tags":[],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["real-world-evidence"],"trials":[],"people":[],"bottlenecks":["b-data-silos","b-real-world-evidence"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A standing federated network with pre-approved study templates can answer a comparative effectiveness question on more than 10,000 patients in under six months, at least five times faster than a bespoke pooled analysis.","rationale":"OHDSI's LEGEND studies have run across tens of millions of records in months. Federated analysis avoids the legal negotiation that is the actual rate-limiting step, because no identifiable data leave the controller.","test":"Run three pre-registered oncology questions (for example, real-world survival on first-line immunotherapy by performance status) across at least 20 centres; measure time to result and concordance with existing trial or registry estimates.","maturity":"early-clinical","actor":"data","cost":"medium","horizonYears":3},{"id":"idea-fra-adc-sequencing-ovarian","kind":"idea","name":"Sequence folate-receptor ADCs by payload class","aka":[],"tldr":"Three FRα ADCs carry different poisons (tubulin, hemiasterlin, topoisomerase). Use them in sequence rather than treating them as interchangeable.","summary":"Three folate receptor alpha antibody-drug conjugates in ovarian cancer share an antigen but not a payload: mirvetuximab soravtansine carries the tubulin agent DM4 and is used only in FRalpha-high tumours, luveltamab tazevibulin carries a hemiasterlin, and rinatabart sesutecan carries the topoisomerase 1 inhibitor exatecan. The idea is to sequence them by payload class rather than treating them as interchangeable. The rationale is that resistance to a tubulin payload, through tubulin mutations or efflux, is not expected to cross to a topoisomerase payload, and FRalpha is rarely lost at progression. The test would be a post-mirvetuximab cohort of RAINFOL-02 or a phase 2 with paired biopsies; the evidence is preclinical, and the idea connects to the general rule of payload-class switching.","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT04209855: MIRASOL / GOG-3045","url":"https://clinicaltrials.gov/study/NCT04209855"}],"tags":[],"related":["idea-payload-switching"],"cancers":["ovarian"],"sections":[],"technologies":[],"targets":["folr1"],"drugs":["mirvetuximab-soravtansine","rinatabart-sesutecan","luveltamab-tazevibulin"],"companies":[],"institutions":[],"pathways":[],"terms":["adc-sequencing"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-mirasol-nejm-2023","paper-mirvetuximab-soravtansine-ovarian-j-clin-oncol-2023","paper-mirvetuximab-soravtansine-ovarian-ann-oncol-2021"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Patients progressing on mirvetuximab retain FRα and respond to a TOP1-payload FRα ADC at rates similar to ADC-naive patients.","rationale":"Payload-specific resistance (tubulin mutations, efflux) does not cross to topoisomerase payloads; FRα PET or repeat biopsy can confirm antigen persistence.","test":"Post-mirvetuximab cohort in RAINFOL-02 or a dedicated phase 2 with paired biopsies for FRα and payload-resistance markers.","maturity":"preclinical-evidence"},{"id":"idea-her2-adc-sequencing-payload","kind":"idea","name":"Sequencing HER2 ADCs by payload after T-DXd","aka":[],"tldr":"When Enhertu stops working, the next ADC should probably carry a different kind of payload, such as the tubulin inhibitors in Kadcyla or ARX788, rather than another topoisomerase drug.","summary":"The idea is to choose the next HER2 antibody-drug conjugate after trastuzumab deruxtecan by payload class: a tubulin-inhibitor ADC such as trastuzumab emtansine, ARX788 or disitamab vedotin rather than another topoisomerase 1 payload. T-DXd is now used first line and in early disease, so most later HER2 ADC use will follow it; resistance often spares HER2 expression but involves TOP1 or SLFN11 changes, and TOP1 payloads show cross-resistance. The hypothesis is that a tubulin-payload ADC gives a higher response rate and longer progression-free survival than a second TOP1-payload ADC when HER2 is retained. The test is a randomised phase 2 stratified by HER2 immunohistochemistry on a progression biopsy, measuring SLFN11 and TOP1; the evidence is preclinical.","asOf":"2026-09-07","links":[{"label":"DESTINY-Breast03: trastuzumab deruxtecan beats T-DM1 as second-line treatment of HER2-positive metastatic breast cancer (New England Journal of Medicine 2022)","url":"https://doi.org/10.1056/NEJMoa2115022"},{"label":"DESTINY-Breast04: trastuzumab deruxtecan works in HER2-low breast cancer, creating a new treatable group (New England Journal of Medicine 2022)","url":"https://doi.org/10.1056/NEJMoa2203690"}],"tags":[],"related":[],"cancers":["breast-her2-positive"],"sections":[],"technologies":["adc"],"targets":[],"drugs":["trastuzumab-deruxtecan","trastuzumab-emtansine","arx788","disitamab-vedotin"],"companies":[],"institutions":[],"pathways":[],"terms":["adc-sequencing"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-katherine-nejm-2019","paper-trastuzumab-deruxtecan-breast-her2-positive-n-engl-j-med-2020","paper-kristine-lancet-oncol-2018"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"After T-DXd progression with retained HER2 expression, a tubulin-payload HER2 ADC produces a higher ORR and longer PFS than a second TOP1-payload HER2 ADC.","rationale":"Cross-resistance among TOP1 payloads has been observed in breast cancer retrospective series; HER2 remains expressed in most T-DXd-resistant tumours.","test":"Randomised phase 2 of T-DM1 or ARX788 versus a TOP1-payload HER2 ADC after T-DXd, stratified by HER2 IHC on progression biopsy; measure SLFN11 and TOP1 status.","maturity":"preclinical-evidence"},{"id":"idea-tr2-smart-sequencing-adc","kind":"idea","name":"Sequential multiple-assignment randomised trials to find the best order of ADCs","aka":[],"tldr":"Patients are randomised at each decision point, not just at the start, so one trial can compare whole treatment sequences rather than single drugs.","summary":"SMART designs, standard in behavioural science, randomise patients again at progression. In metastatic breast cancer where three ADCs (T-DXd, sacituzumab, Dato-DXd) and multiple payload classes compete, a SMART would compare sequences (A then B versus B then A, payload switch versus antigen switch) with a primary endpoint of time to failure of the second line or overall survival.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Too many combinations to test): Palmer & Sorger, Combination cancer therapy can confer benefit via patient-to-patient variability without drug additivity or synergy (Cell 2017)","url":"https://doi.org/10.1016/j.cell.2017.11.009"}],"tags":[],"related":["idea-payload-switching","idea-her2-adc-sequencing-payload","adc-after-adc-caution"],"cancers":["breast-hr-positive","tnbc"],"sections":[],"technologies":["adc"],"targets":[],"drugs":["trastuzumab-deruxtecan","sacituzumab-govitecan","datopotamab-deruxtecan"],"companies":[],"institutions":[],"pathways":[],"terms":["adc-sequencing","efflux-pump"],"trials":[],"people":[],"bottlenecks":["b-combination-space","b-resistance"],"keyPapers":["paper-palmer-cell"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A SMART in HER2-low metastatic breast cancer identifies a sequence with at least four months longer overall survival than the most common real-world sequence.","rationale":"Sequences are almost never randomised, so guidelines are built from single-line trials with different populations. Cross-resistance among topoisomerase-1 payload ADCs makes order a plausibly large effect.","test":"A cooperative-group SMART with two re-randomisation points, 600 patients, embedding SLFN11 and TOP1 biomarker sampling at each progression.","maturity":"speculative","actor":"research","cost":"large","horizonYears":5},{"id":"idea-data-sequestered-prospective-benchmarks","kind":"idea","name":"Sequestered, prospectively collected benchmark datasets that no one can train on","aka":[],"tldr":"Keep test datasets locked away and collect them going forward, so AI claims are checked on data the developers have never seen and could not have memorised.","summary":"Public benchmarks leak into training sets and go stale; retrospective validation flatters models. The proposal is a set of sequestered evaluation datasets for key cancer AI tasks (mammography, lung nodules, prostate biopsy, HER2 scoring, ctDNA calls), collected prospectively from multiple sites and countries, held by a neutral body, with evaluation only via submission of the model or an API, and results published. NIST's face recognition testing and the MICCAI challenge model are precedents.","asOf":"2026-09-08","links":[{"label":"NIST FRTE (face recognition evaluation)","url":"https://www.nist.gov/programs-projects/face-technology-evaluations-frtefate"}],"tags":[],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":["radiology-ai-screening","digital-pathology-ai","ctdna"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-ai-validation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Performance on sequestered prospective data will be materially lower than published performance for most models, and public reporting will shift developers toward robust training and honest claims.","rationale":"In face recognition, NIST's sequestered testing became the de facto standard buyers rely on; in medical imaging, external test sets consistently reveal performance drops that published papers omit.","test":"Stand up two sequestered benchmarks; evaluate all willing vendors; publish results alongside their published claims; repeat annually to measure whether the gap narrows.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":2},{"id":"idea-fund-replication-set-aside","kind":"idea","name":"Set aside 3% of grant budgets to replicate findings before translation","aka":[],"tldr":"Before spending millions to turn a lab finding into a drug, spend a little to have an independent lab check it is real. Funders would reserve a small slice of money for exactly this.","summary":"Funders reserve 3% of research budgets for independent, pre-registered replications of high-impact preclinical findings that are about to receive translational investment (IND-enabling work, company formation, phase 1). Replication is done by contract labs or a network of academic 'replication cores' with blinded protocols agreed with the original authors. The Reproducibility Project: Cancer Biology found that many landmark effects were smaller or absent when repeated; catching this before translation saves far more than it costs.","asOf":"2026-09-08","links":[{"label":"Reproducibility Project: Cancer Biology","url":"https://www.cos.io/rpcb"}],"tags":[],"related":["idea-fund-organoid-translation-gate","idea-fund-ind-enabling-fund"],"cancers":[],"sections":[],"technologies":["pdx-models","organoids","crispr-screens"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-funding-allocation","b-reproducibility","b-translational-valley"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Systematic replication before translational investment finds at least 30% of candidate findings non-reproducible or materially weaker, and translational programmes that pass replication reach phase 1 with fewer late-stage preclinical failures than unreplicated ones.","rationale":"The Reproducibility Project: Cancer Biology reproduced effects at roughly half the original magnitude on average; Bayer and Amgen internal replication efforts reported majority failure. Independent verification is standard before major capital deployment in every other industry.","test":"Pilot with one translational fund: replicate the key experiment for every asset before IND-enabling money is released, and compare downstream attrition with the fund's historical record.","maturity":"speculative","actor":"research","cost":"medium","horizonYears":3},{"id":"idea-prev-ai-mammogram-risk-intervals","kind":"idea","name":"Set each woman's mammogram interval from her last mammogram, using AI risk","aka":[],"tldr":"Instead of every woman every two or three years, an AI reading of the current mammogram would set who comes back in one year and who can safely wait four.","summary":"Image-based risk models (Mirai and commercial density-plus-AI scores) outperform Tyrer-Cuzick for five-year risk. MyPeBS and WISDOM test risk-based intervals using classical risk plus polygenic scores. Propose a national programme trial where the AI score on the index mammogram assigns one-, three-, or four-year recall, with interval cancer rate and advanced-cancer incidence as endpoints.","asOf":"2026-09-08","links":[{"label":"MyPeBS","url":"https://www.mypebs.eu"},{"label":"WISDOM study","url":"https://www.wisdomstudy.org"}],"tags":[],"related":[],"cancers":["breast-hr-positive","tnbc"],"sections":["early-detection","imaging"],"technologies":["mammography","radiology-ai-screening"],"targets":[],"drugs":[],"companies":["lunit"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-early-detection","b-overdiagnosis"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"AI-image-based intervals reduce stage II+ cancer incidence by at least 15% at equal or lower total mammogram volume compared with fixed intervals.","rationale":"Most interval cancers occur in a small high-risk stratum identifiable on the prior image; most low-risk women get no benefit from frequent recall.","test":"Cluster-randomised comparison within an existing programme (e.g. NHS Breast Screening Programme sites) of fixed versus AI-assigned intervals; five-year advanced-cancer endpoint.","maturity":"early-clinical","actor":"clinic","cost":"medium","horizonYears":6},{"id":"idea-tr1-incidence-weighted-enrolment-targets","kind":"idea","name":"Set trial enrolment targets from who actually gets the disease, and publish progress live","aka":[],"tldr":"Each trial would set its target mix of patients from cancer registry data on who gets that cancer, by age, sex and ethnicity, and show a public running tally so gaps are visible while there is still time to fix them.","summary":"Sponsors derive enrolment targets per stratum from incidence data (SEER, GLOBOCAN, national registries) for the indication and the countries where the trial runs, publish the targets in the registry record, and update enrolled counts quarterly. Recruitment resources are reallocated during the trial toward under-enrolled strata (site additions, navigators, translated materials).","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Trials do not represent the people who get cancer): Loree et al., Disparity of race reporting and representation in trials leading to cancer drug approvals (JAMA Oncology 2019)","url":"https://doi.org/10.1001/jamaoncol.2019.1870"}],"tags":[],"related":["seer","globocan","clinicaltrials-gov"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-diversity","b-trial-enrolment"],"keyPapers":["paper-loree-jama-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Trials with live public stratum tallies will finish closer to incidence-weighted targets than trials with static goals, because course correction happens during accrual rather than being noted at the end.","rationale":"Enrolment gaps are usually discovered at analysis, too late to correct. Live dashboards changed vaccination and screening coverage by making gaps actionable.","test":"Randomise a sponsor's new trials to live public tallies or internal-only tracking and compare final representativeness.","maturity":"early-clinical","actor":"industry","cost":"small","horizonYears":2},{"id":"idea-moon-sexual-health-as-toxicity-domain","kind":"idea","name":"Sexual health assessed and treated as a standard toxicity domain","aka":[],"tldr":"Cancer treatment often damages sexual function and intimacy, and almost nobody asks. Make it a routine question with a clinic to refer to.","summary":"Sexual dysfunction after pelvic surgery, radiotherapy, endocrine therapy and stem cell transplant is very common and is among the least discussed toxicities. The proposal is routine screening with a brief validated item set at treatment milestones, a referral pathway to sexual health services (pelvic floor physiotherapy, vaginal and erectile therapies, counselling), and inclusion of sexual function as a PRO domain in trials of pelvic and endocrine treatments.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Toxicity and quality of life are undervalued): Di Maio et al., Symptomatic toxicities experienced during anticancer treatment: agreement between patient and physician reporting (JCO 2015)","url":"https://doi.org/10.1200/JCO.2014.57.9334"}],"tags":[],"related":[],"cancers":["prostate","cervical","colorectal","breast-hr-positive"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol","b-survivorship"],"keyPapers":["paper-di-maio-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Routine screening and referral increases treatment of sexual dysfunction severalfold and improves patient-reported quality of life and adherence to endocrine therapy.","rationale":"Under-treatment is driven by embarrassment and absent pathways, not absent treatments; adherence to endocrine therapy is known to fall with sexual side-effects.","test":"Implementation trial in prostate, cervical, rectal and breast cancer clinics with screening rates, referral, and quality of life at 12 months as endpoints.","maturity":"early-clinical","actor":"clinic","cost":"small","horizonYears":2},{"id":"idea-cost-vial-sharing-dose-rounding","kind":"idea","name":"Share vials and round doses to stop throwing away expensive drug","aka":[],"tldr":"Weight-based doses rarely match vial sizes, so the leftover is discarded and still billed; closed-system vial sharing and rounding doses to the nearest vial within 10% eliminate most of that waste.","summary":"Medicare pays for discarded drug under the JW modifier and, since 2023, requires refunds from manufacturers for waste above 10% under the Infrastructure Investment and Jobs Act. Pharmacies can avoid the waste in the first place: closed-system transfer devices extend the in-use stability of single-dose vials so one vial serves several patients, and dose banding (rounding to the nearest vial size within a defined tolerance) is standard in the NHS. Both are cheap and can be implemented by a hospital pharmacy in months.","asOf":"2026-09-10","links":[{"label":"CMS: Discarded drug refunds (JW and JZ modifiers) (page moved; nearest live section)","url":"https://www.cms.gov/medicare/payment/part-b-drugs/"}],"tags":[],"related":[],"cancers":[],"sections":["chemotherapy","immunotherapy"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-drug-pricing","b-dose-optimisation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Dose rounding and vial sharing will reduce discarded drug for the ten highest-spend Part B oncology drugs by more than 70% in participating centres.","rationale":"The NHS national dose-banding tables and multiple US single-centre studies report six- and seven-figure annual savings per institution.","test":"Pharmacy-level before-and-after audits of JW-modifier billing and drug spend, with a registry of any stability or safety issues.","maturity":"being-tested-at-scale","actor":"clinic","cost":"small","horizonYears":1},{"id":"idea-tr2-shared-control-network","kind":"idea","name":"Shared concurrent control arms across sponsors' trials in the same setting","aka":[],"tldr":"When five companies each run a trial against the same standard treatment in the same patients, let them pool the standard-treatment patients so fewer people are randomised to the old drug.","summary":"Concurrent trials in the same indication each recruit their own control arm on identical standard of care. A pre-agreed common data model, shared eligibility core and a neutral data custodian would let sponsors borrow concurrent (not historical) controls with regulatory pre-agreement, as pioneered by the Alzheimer's Disease EPOCH and the Bayesian borrowing frameworks in paediatric oncology.","asOf":"2026-09-08","links":[{"label":"FDA complex innovative trial design programme","url":"https://www.fda.gov/drugs/development-resources/complex-innovative-trial-design-meeting-program"}],"tags":[],"related":["clinicaltrials-gov"],"cancers":["urothelial","pancreatic"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["basket-umbrella-platform","hazard-ratio"],"trials":[],"people":[],"bottlenecks":["b-combination-space","b-trial-enrolment"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A shared-control network in first-line metastatic urothelial or pancreatic cancer reduces total patients randomised to control by at least 40% across participating trials without inflating type I error beyond pre-specified bounds.","rationale":"Concurrent controls avoid the drift and selection bias that make historical controls unreliable. FDA's complex innovative design programme and EMA have both accepted Bayesian borrowing when exchangeability is demonstrated.","test":"Pilot with three sponsors in one indication under FDA's complex innovative trial design meeting programme; simulate operating characteristics, then run and compare control-arm outcomes across sponsors for exchangeability.","maturity":"early-clinical","actor":"regulator","cost":"medium","horizonYears":4},{"id":"idea-fund-shared-personalised-therapy-gmp","kind":"idea","name":"Shared modular GMP facilities for academic personalised vaccines and cell products","aka":[],"tldr":"Personalised cancer vaccines and cell therapies need a manufacturing run for each patient, and universities cannot afford their own plants. Regional closed, automated, modular GMP facilities offering slots to academic trials at cost, with common release testing and a shared quality system, modelled on the UK Cell and Gene Therapy Catapult centre, would let academic groups run these trials.","summary":"Regional facilities with closed, automated, modular manufacturing (mRNA and peptide neoantigen vaccines, autologous CAR-T and TIL, dendritic cell products) offering slots to academic trials at cost, with common release testing, digital batch records and a shared quality management system accepted by regulators. Modelled on the UK's Cell and Gene Therapy Catapult manufacturing centre and CIRM's Alpha Clinics, but explicitly for oncology personalised therapies where academic groups hold the biology but cannot manufacture. Coupled with the hospital-exemption registry and public CAR-T network, this is the manufacturing layer of an academic personalised-therapy system.","asOf":"2026-09-08","links":[{"label":"Cell and Gene Therapy Catapult","url":"https://ct.catapult.org.uk/"}],"tags":[],"related":["idea-fund-translational-institutes-gmp","idea-fund-public-car-t-manufacturing","idea-fund-academic-adc-bispecific-platform"],"cancers":[],"sections":[],"technologies":["neoantigen-mrna-vaccine","car-t","til-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-translational-valley","b-manufacturing-cell-therapy"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Shared facilities cut the manufacturing cost per patient for academic personalised products by at least half and enable at least ten academic personalised-therapy trials per facility per year, compared with one or two in most academic centres today.","rationale":"The Cell and Gene Therapy Catapult has supported dozens of companies and academic groups with shared GMP; automated closed systems reduce staff and cleanroom costs that dominate academic manufacturing. Academic neoantigen vaccine trials have been limited by manufacturing slots, not by scientific readiness.","test":"Fund one facility for three years and track trials served, cost per product and batch success rate against academic in-house manufacturing benchmarks.","maturity":"early-clinical","actor":"engineering","cost":"large","horizonYears":4},{"id":"idea-tr2-reference-model-panels","kind":"idea","name":"Shared reference organoid and PDX panels that every lab can test against","aka":[],"tldr":"If every lab had access to the same set of well-characterised tumour models, results could be compared directly instead of each lab using its own private models.","summary":"Organoid and patient-derived xenograft results are hard to compare because models differ between labs. A curated reference panel (for example 50 organoids and 50 PDX models per major cancer, fully characterised, distributed at cost by a repository such as the Human Cancer Models Initiative or EurOPDX) with standard culture protocols and published baseline drug responses would serve as the common ground for method comparison and replication.","asOf":"2026-09-08","links":[{"label":"Human Cancer Models Initiative","url":"https://www.cancer.gov/ccg/research/functional-genomics/hcmi"},{"label":"EurOPDX","url":"https://www.europdx.eu/"}],"tags":[],"related":["cancer-models","idea-tr2-organoid-matrix-atlas","idea-tr2-reference-compound-panels"],"cancers":[],"sections":[],"technologies":["organoids","pdx-models"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-reproducibility","b-preclinical-models"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Drug-response results generated on the reference panel in different laboratories will show inter-laboratory concordance above 0.8, and findings validated on the panel will replicate more often than those on private models.","rationale":"Reference strains and lines underpin reproducibility in microbiology and immunology; oncology models have proliferated without a reference set.","test":"Distribute the panel to ten laboratories; run a common drug set; measure concordance; compare with historical cross-lab discordance.","maturity":"preclinical-evidence","actor":"philanthropy","cost":"medium","horizonYears":3},{"id":"idea-splice-neoantigens","kind":"idea","name":"Shared splice-derived neoantigens as off-the-shelf vaccine targets","aka":[],"tldr":"Mutations in the RNA splicing genes SF3B1, SRSF2 and U2AF1 produce the same mis-spliced proteins in patient after patient with MDS, CLL or uveal melanoma. If fragments of those proteins are displayed on common HLA molecules and seen by T cells, one off-the-shelf vaccine or TCR-T therapy could serve every SF3B1-mutant patient instead of being built per person.","summary":"This idea proposes shared splice-derived neoantigens as off-the-shelf vaccine targets: mutations in the RNA splicing machinery make the same abnormal proteins recur from patient to patient, so one vaccine could serve all who carry the mutation. SF3B1, SRSF2 and U2AF1 mutations produce recurrent mis-spliced transcripts in MDS, CLL and uveal melanoma, some predicted to be HLA-presented, opening the way to Off-the-shelf cancer vaccines or TCR-T cell therapy. The hypothesis is that recurrent splice-junction neoantigens from SF3B1-mutant cells are presented on common HLA alleles and elicit T-cell responses, enabling a shared vaccine for SF3B1-mutant MDS and CLL. The test runs from an immunopeptidomic screen using Proteomics & phosphoproteomics to a phase 1 shared vaccine in high-risk SF3B1-mutant MDS.","asOf":"2026-09-08","links":[{"label":"Kahles et al., Comprehensive analysis of alternative splicing across tumours from 8,705 patients (Cancer Cell 2018)","url":"https://doi.org/10.1016/j.ccell.2018.07.001"}],"tags":["mechanism","open-question"],"related":[],"cancers":["aml","cll","melanoma"],"sections":[],"technologies":["shared-antigen-vaccine","tcr-t","proteomics"],"targets":[],"drugs":[],"companies":[],"institutions":["mskcc","fred-hutch"],"pathways":["rna-splicing","antigen-presentation-immunoediting"],"terms":["neoantigen"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-kahles-cancer-cell"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Recurrent splice-junction neoantigens from SF3B1-mutant cells are presented on common HLA alleles and elicit T-cell responses, enabling a shared vaccine for SF3B1-mutant MDS and CLL.","rationale":"Immunopeptidomics has detected splice-derived peptides; SF3B1 K700E is recurrent; shared-antigen platforms (KRAS vaccines, PRAME TCR) prove the model.","test":"Immunopeptidomic screen of SF3B1-mutant primary cells for HLA-presented splice peptides, T-cell reactivity assays in patients, then a phase 1 shared vaccine in high-risk SF3B1-mutant MDS.","maturity":"speculative"},{"id":"idea-fund-benefit-indexed-exclusivity","kind":"idea","name":"Shorter exclusivity for later-in-class drugs without added benefit","aka":[],"tldr":"The fifth PD-1 antibody that is no better than the first should not get the same market protection as the first. Exclusivity would shrink for copies that add nothing.","summary":"The mirror image of value-based extension: for the third and subsequent entrants in a mechanistic class, regulatory data exclusivity is reduced (for example from eight to four years) unless a head-to-head trial demonstrates superiority or a clinically meaningful advantage (toxicity, route, population) graded on a public scale such as ESMO-MCBS. This does not block approval, which remains safety- and efficacy-based, but changes the return profile of me-too development so that capital moves to unmet needs. Capital diverted from copies is the point; the risk is reduced price competition within class, which can be offset by an abbreviated pathway for biosimilar-like entrants.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Incentives reward me-too drugs and marginal gains): Upadhaya et al., PD1/PDL1 inhibitor clinical trial landscape (Nat Rev Drug Discov 2022)","url":"https://doi.org/10.1038/d41573-022-00030-4"}],"tags":[],"related":["idea-fund-value-based-patent-extension","idea-fund-abbreviated-pathway-me-too-biologics"],"cancers":[],"sections":[],"technologies":[],"targets":["pd1","trop2"],"drugs":["pembrolizumab","nivolumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-incentive-misalignment","b-drug-pricing"],"keyPapers":["paper-upadhaya-nat-rev-drug-discov"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Benefit-indexed exclusivity reduces the number of later-in-class oncology programmes entering phase 3 without a superiority design by at least a third within five years and increases the share of pipeline assets on novel targets.","rationale":"Portfolio analyses document a dozen or more checkpoint inhibitors and TROP2 ADCs in parallel development, each expecting a share of the same market. Firms respond to exclusivity rules (orphan and paediatric exclusivity changed behaviour rapidly), so trimming reward for redundancy should redirect investment.","test":"Simulate the rule against the past decade of approvals to estimate affected products, consult industry, and legislate a sunset pilot with pre-registered indicators of pipeline composition.","maturity":"speculative","actor":"policy","cost":"small","horizonYears":5},{"id":"idea-shortened-venetoclax","kind":"idea","name":"Shorter venetoclax courses in unfit AML","aka":[],"tldr":"Give venetoclax for 7 or 14 days per cycle instead of 28 to cut infections and low blood counts without losing the benefit.","summary":"The idea is to give venetoclax for 7 or 14 days per 28-day cycle, rather than continuously, when combined with azacitidine or oral decitabine-cedazuridine in acute myeloid leukaemia patients unfit for intensive chemotherapy. Cytopenias and infections are the main cause of early death on venetoclax-azacitidine, marrow blasts clear within two weeks, and continued exposure mainly suppresses normal blood cell production. Retrospective and small prospective series show similar remission rates with shorter courses, against the 28-day schedule of VIALE-A. The hypothesis is that 14 days per cycle is non-inferior for overall survival with less severe infection; the test is a randomised non-inferiority trial, addressing the wrong-doses and older-patient bottlenecks.","asOf":"2026-09-07","links":[{"label":"VIALE-A: azacitidine and venetoclax in previously untreated acute myeloid leukaemia (NEJM 2020)","url":"https://doi.org/10.1056/NEJMoa2012971"}],"tags":[],"related":[],"cancers":["aml"],"sections":[],"technologies":[],"targets":[],"drugs":["venetoclax","azacitidine","decitabine-cedazuridine"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["viale-a"],"people":[],"bottlenecks":[],"keyPapers":["paper-viale-a-venetoclax-azacitidine-nejm-2020","paper-aza-aml-001-dombret-blood-2015","paper-azacitidine-aml-j-clin-oncol-2010"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Venetoclax 14 days per 28-day cycle after cycle 1 is non-inferior to 28 days for OS in unfit AML and reduces grade 3+ infection.","rationale":"Marrow blasts clear within the first two weeks; continued exposure mainly suppresses normal haematopoiesis.","test":"Randomised non-inferiority trial of 14- vs 28-day venetoclax with azacitidine (or oral decitabine-cedazuridine); co-primary OS and febrile neutropenia.","maturity":"early-clinical"},{"id":"idea-acc-pathway-capacity-simulation","kind":"idea","name":"Simulate each hospital's cancer pathway as a queue to find and remove the waits","aka":[],"tldr":"Hospitals rarely know which step, the scanner, the biopsy, the pathologist or the clinic slot, is causing the queue. Modelling the pathway like a factory line shows where a small change would remove weeks of waiting.","summary":"Discrete-event simulation and queueing analysis are standard in manufacturing and logistics but rarely applied to cancer diagnostic pathways, where a mismatch between weekly clinic capacity and scanner slots can create long waits that no single department sees. A reusable model fed by routine timestamp data would locate the binding constraint per pathway and quantify the effect of interventions before they are made.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Fragmented care and guideline gaps): Hanna et al., Mortality due to cancer treatment delay: systematic review and meta-analysis (BMJ 2020)","url":"https://doi.org/10.1136/bmj.m4087"}],"tags":[],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-care-fragmentation","b-workforce"],"keyPapers":["paper-hanna-bmj"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Hospitals using pathway simulation to target interventions will reduce the referral-to-treatment interval for at least two tumour pathways by 25% within a year, at lower cost than untargeted capacity expansion.","rationale":"Operations research routinely finds that a small number of constraints determine throughput and that adding capacity elsewhere achieves nothing; cancer pathways have the same structure.","test":"Apply the model in five hospitals, implement the top recommendation in each, and measure interval change against five matched hospitals.","maturity":"speculative","actor":"engineering","cost":"small","horizonYears":1},{"id":"idea-tr1-eligibility-impact-statement","kind":"idea","name":"Simulate eligibility against real-world data before every protocol is locked","aka":[],"tldr":"Before a trial is finalised, run its entry rules against records of real patients with that cancer and report what fraction would qualify. If it is under half, explain why.","summary":"An 'eligibility impact statement' in the protocol: the criteria are applied to a de-identified real-world cohort (EHR-derived or registry) and the eligible fraction, its demographic profile and the criteria excluding the most patients are reported. Work using real-world oncology data has shown that relaxing common criteria roughly doubles the eligible population with little change in estimated treatment effect.","asOf":"2026-09-08","links":[{"label":"Evaluating eligibility criteria of oncology trials using real-world data and AI (Nature 2021)","url":"https://www.nature.com/articles/s41586-021-03430-5"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["ai-trial-matching"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["real-world-evidence"],"trials":[],"people":[],"bottlenecks":["b-trial-enrolment","b-real-world-evidence"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Protocols with a pre-lock eligibility impact statement will end up with a higher real-world eligible fraction and faster accrual than protocols without one, because the statement makes the cost of each criterion visible to the team writing it.","rationale":"Teams over-restrict because restriction feels safe and its cost is invisible. A number on the page changes the conversation; this is how carbon and cost-impact statements work in other fields.","test":"A sponsor introduces the statement for half of its new protocols by random allocation of programmes and compares eligible fraction and accrual speed after 18 months.","maturity":"early-clinical","actor":"industry","cost":"small","horizonYears":1},{"id":"idea-single-dose-hpv-self-sampling-elimination","kind":"idea","name":"Single-dose HPV vaccination plus HPV self-sampling to reach WHO elimination in low-income countries","aka":[],"tldr":"One shot for girls and a mail-in swab for women could hit the WHO 90-70-90 targets at a fraction of the cost of the traditional three-dose, clinic-based model.","summary":"KEN SHE showed 97.5% single-dose efficacy; self-sampled HPV PCR matches clinician sampling; thermal ablation enables screen-and-treat. Modelling (Lancet Global Health 2024) suggests single-dose schedules could make elimination feasible in most low-income settings within the century, but coverage of girls is still ~27% globally.","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT03675256: KEN SHE (single-dose HPV vaccine)","url":"https://clinicaltrials.gov/study/NCT03675256"}],"tags":[],"related":[],"cancers":["cervical"],"sections":[],"technologies":["hpv-vaccine","hpv-testing","precancer-ablation"],"targets":[],"drugs":["gardasil-9"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["ken-she"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Countries adopting single-dose HPV vaccination plus HPV self-sampling with screen-and-treat reach 90% vaccination and 70% screening coverage a decade earlier than those on multi-dose, cytology-based programmes.","rationale":"Cost per protected girl halves; self-sampling removes clinic access and stigma barriers; ablation removes the surgeon bottleneck.","test":"Country-level comparisons within the WHO Cervical Cancer Elimination Initiative dashboards, and cluster-randomised implementation trials (e.g., in Kenya, Rwanda, India).","maturity":"being-tested-at-scale"},{"id":"idea-acc-single-fraction-palliative-radiotherapy-default","kind":"idea","name":"Single-fraction radiotherapy as the default for painful bone metastases","aka":[],"tldr":"Randomised trials and meta-analyses show a single 8 Gy radiotherapy session relieves pain from uncomplicated bone metastases as well as ten sessions, with a higher retreatment rate, yet habit and per-fraction payment keep most patients on the longer course. Making one session the default, with an opt-out justification and payment neutrality, would spare patients trips and free machines.","summary":"Multiple randomised trials and meta-analyses show a single 8 Gy fraction is as effective as multi-fraction schedules for pain from uncomplicated bone metastases, with a higher retreatment rate but no difference in overall pain control. Despite guidelines, single-fraction use remains a minority in many countries because of habit and reimbursement. A default protocol with an opt-out justification, plus payment neutrality, would align practice with evidence and release capacity.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Pain relief and palliative care are unavailable to most): WHO fact sheet, Palliative care","url":"https://www.who.int/news-room/fact-sheets/detail/palliative-care"}],"tags":[],"related":[],"cancers":[],"sections":["radiation"],"technologies":["imrt-igrt"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-palliative","b-surgery-radiation-innovation","b-global-access"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Departments adopting single-fraction default will raise single-fraction use for uncomplicated bone metastases above 70% and reduce time to treatment start for palliative referrals, with no change in patient-reported pain response.","rationale":"The evidence is as strong as any in radiotherapy; the barrier is behavioural and financial, both addressable by policy.","test":"Audit fraction use, time to treatment, pain response, and retreatment rates before and after policy change across a national network.","maturity":"being-tested-at-scale","actor":"clinic","cost":"small","horizonYears":1},{"id":"idea-acc-telepathology-district-network","kind":"idea","name":"Slide scanners in district hospitals wired to pathologists anywhere","aka":[],"tldr":"In much of Africa and South Asia there is about one pathologist per million people, so the pathologist, not the tissue sample, is the diagnostic bottleneck. A slide scanner in each district lab, routing images to a pooled roster of pathologists including diaspora volunteers, could give a diagnosis in days instead of months; the gap is scale and financing.","summary":"The bottleneck for cancer diagnosis in much of Africa and South Asia is the pathologist, not the tissue sample. Whole-slide scanners now cost a fraction of what they did, and pathology images travel well. A national or regional network would standardise tissue processing at district labs, scan every slide, route to a shared roster of pathologists (including diaspora volunteers and partner institutions), and track turnaround time as the primary metric. Several pilot networks exist; the gap is scale and sustainable financing.","asOf":"2026-09-08","links":[{"label":"Lancet Commission on diagnostics","url":"https://www.thelancet.com/commissions/diagnostics"}],"tags":[],"related":[],"cancers":[],"sections":["diagnostics"],"technologies":["digital-pathology-ai"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-global-access","b-workforce"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Districts connected to a telepathology network will reduce median biopsy-to-report time to under ten days from more than four weeks, with discordance on second review under 5%.","rationale":"Teleradiology built a global industry on the same logic. Histology processing is cheap and teachable; interpretation is the scarce, movable part.","test":"A stepped-wedge national rollout measuring turnaround time, proportion of cancers with a histological diagnosis before treatment, and cost per case, compared with districts not yet connected.","maturity":"being-tested-at-scale","actor":"engineering","cost":"medium","horizonYears":2},{"id":"idea-bio1-apobec-inhibitor-adjunct","kind":"idea","name":"Slow the tumour's mutation engine with APOBEC inhibitors during targeted therapy","aka":[],"tldr":"Subsets of lung, bladder and breast cancers carry raised APOBEC enzyme activity that keeps generating new mutations, feeding resistance. Blocking APOBEC3 alongside a targeted drug aims not to kill cells but to slow the rate at which resistant variants arise; the inhibitors are still in discovery.","summary":"APOBEC3A and APOBEC3B mutagenesis is elevated in subsets of lung, bladder and breast cancers and has been mechanistically linked to acquired resistance to EGFR inhibitors in preclinical models. Small-molecule APOBEC3 inhibitors are in discovery. The proposal is an anti-evolution adjunct: combine an APOBEC inhibitor with the targeted agent from the first dose, with the aim not of killing cells but of reducing the rate at which resistant variants are generated.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Tumour heterogeneity and clonal evolution): Gerlinger et al., Intratumor heterogeneity and branched evolution (NEJM 2012)","url":"https://doi.org/10.1056/NEJMoa1113205"}],"tags":[],"related":[],"cancers":["nsclc","urothelial"],"sections":[],"technologies":[],"targets":[],"drugs":["osimertinib"],"companies":[],"institutions":[],"pathways":[],"terms":["mutational-signature"],"trials":[],"people":[],"bottlenecks":["b-tumor-heterogeneity","b-resistance"],"keyPapers":["paper-flaura-nejm-2018","paper-osimertinib-nsclc-n-engl-j-med-2017","paper-osimertinib-nsclc-n-engl-j-med-2020"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"APOBEC3 inhibition during osimertinib treatment reduces the APOBEC-signature fraction of new mutations in progression samples and extends progression-free survival in APOBEC-high tumours.","rationale":"Genetic APOBEC3A deletion delays resistance in EGFR-mutant xenografts; the signature is measurable in ctDNA, giving a pharmacodynamic biomarker and a patient-selection tool.","test":"Confirm in vivo delay of resistance with a tool compound across three driver models; if reproduced, a phase 1b of the first clinical APOBEC inhibitor with osimertinib in APOBEC-high EGFR-mutant lung cancer with serial ctDNA signature analysis.","maturity":"preclinical-evidence","actor":"industry","cost":"large","horizonYears":7},{"id":"idea-tr2-writeup-grants","kind":"idea","name":"Small grants that pay scientists to write up abandoned projects","aka":[],"tldr":"Failed projects are not published because nobody has the time. Paying for a few months of writing would recover years of otherwise lost work.","summary":"Every lab has unpublished null results from completed projects: a hypothesis tested carefully that did not hold. The cost of writing them up is a few months of a postdoc's time with no career reward. A funder programme offering short 'completion grants' conditional on deposit in a negative-results venue would recover this work at very low cost per result.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Failures are hidden): Anderson et al., Compliance with results reporting at ClinicalTrials.gov (NEJM 2015)","url":"https://doi.org/10.1056/NEJMsa1409364"}],"tags":[],"related":["idea-tr2-negative-results-journal","idea-tr2-preclinical-negative-registry"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-negative-results","b-funding-allocation"],"keyPapers":["paper-anderson-n-engl-j-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A programme of 200 completion grants per year produces at least 150 published or deposited null results per year, at a cost per result under one tenth of a typical project grant.","rationale":"Surveys suggest a substantial share of completed studies are never published, most often because the result was null. The barrier is effort, not data.","test":"Pilot with 50 grants; measure completion rate, time to deposit and downstream views or citations.","maturity":"speculative","actor":"philanthropy","cost":"small","horizonYears":1},{"id":"idea-bio1-rna-targeting-small-molecules","kind":"idea","name":"Small molecules that cut the RNA message of an undruggable oncogene","aka":[],"tldr":"If the protein cannot be drugged, target the message that makes it. Small molecules can now recognise folded shapes in RNA and recruit an enzyme that chops it up.","summary":"Ribonuclease-targeting chimeras (RIBOTACs) and RNA-binding small molecules bind structured motifs in oncogenic transcripts and recruit RNase L. Precedent exists for microRNA precursors and for the splicing modulator class approved in spinal muscular atrophy, which proved that oral small molecules can act on RNA in humans. Candidate cancer targets include MYC regulatory elements, oncogenic lncRNAs and undruggable transcription factor messages.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The undruggable drivers): Dang et al., Drugging the 'undruggable' cancer targets (Nature Reviews Cancer 2017)","url":"https://doi.org/10.1038/nrc.2017.36"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["antisense-sirna","rna-seq"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-undruggable-targets"],"keyPapers":["paper-dang-nat-rev-cancer"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"An RNA-targeted degrader reduces the target transcript by more than 70 percent in tumour tissue after oral dosing, with corresponding protein loss and tumour growth inhibition.","rationale":"RNA structure gives sequence-specific recognition without needing a protein pocket, and risdiplam shows the pharmacology is achievable orally in patients.","test":"Select one oncogene with a well-characterised structured motif; run structure-based screening, confirm on-target transcript loss by RNA sequencing with off-target transcriptome profiling, then test in xenografts.","maturity":"speculative","actor":"research","cost":"medium","horizonYears":8},{"id":"idea-tr1-smart-designs-for-adaptive-strategies","kind":"idea","name":"SMART designs to test treatment strategies, not just single drugs","aka":[],"tldr":"Real treatment is a series of decisions: start with this, switch to that if it fails. Sequential multiple-assignment randomised trials test whole strategies by randomising patients again at each decision point.","summary":"SMART designs re-randomise participants at pre-specified decision points (e.g., at first progression or at ctDNA rise) to compare adaptive treatment strategies, estimating the best dynamic regime rather than the best single drug. Used in behavioural science and some leukaemia trials, rarely in solid tumours. Combined with a platform structure, this can address resistance-driven sequencing.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Trial design, endpoints and cost): Davis et al., Availability of evidence of benefits on survival and quality of life of cancer drugs approved by EMA 2009-13 (BMJ 2017)","url":"https://doi.org/10.1136/bmj.j4530"}],"tags":[],"related":["prostate-roadmap","idea-prostate-randomise-the-sequence-not-only-the-drugs"],"cancers":["colorectal","prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["resistance","ctdna"],"trials":[],"people":[],"bottlenecks":["b-trial-design","b-resistance"],"keyPapers":["paper-davis-bmj"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"SMART trials will identify treatment strategies that improve OS over the best single-decision comparison in at least one common solid tumour setting within five years.","rationale":"Sequencing and switching decisions drive outcomes as much as the choice of first drug; single-decision RCTs cannot evaluate them, and observational sequencing data are confounded.","test":"Run one SMART in metastatic colorectal or prostate cancer comparing switching rules (radiographic vs ctDNA-triggered) and second-line choices, with OS as the primary endpoint.","maturity":"speculative","actor":"research","cost":"medium","horizonYears":4},{"id":"idea-prev-weight-loss-auto-alert","kind":"idea","name":"Smart scales and health records flag unexplained weight loss for a cancer check","aka":[],"tldr":"Losing weight without trying is one of the strongest signs of hidden cancer, but it is rarely measured. Automatic alerts from recorded weights could prompt a check-up.","summary":"Unexpected weight loss in primary care carries a 1-3% cancer risk within six months, higher with other signs, yet weights are recorded sporadically. Propose a primary-care algorithm, with opt-in consumer scale or wearable integration, that flags 5% or more unintentional loss over six months and prompts a structured blood-and-imaging check.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The hardest cancers are found late): Crosby et al., Early detection of cancer (Science 2022)","url":"https://doi.org/10.1126/science.aay9040"}],"tags":[],"related":[],"cancers":[],"sections":["early-detection"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-early-detection"],"keyPapers":["paper-crosby-science"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Automated weight-loss alerts increase cancer diagnoses via non-emergency routes and reduce emergency presentations by at least 10% in the alerted population.","rationale":"Weight loss precedes diagnosis by months; the signal is free and the action is cheap.","test":"Run a cluster RCT of the alert in primary care networks; the endpoints are route to diagnosis and stage.","maturity":"speculative","actor":"clinic","cost":"small","horizonYears":3},{"id":"idea-prev-smokefree-generation-evaluation","kind":"idea","name":"Smoke-free generation laws with a built-in evaluation across countries","aka":[],"tldr":"Banning tobacco sales to anyone born after a set year, as the UK is doing, could end smoking within a generation. Adopting countries should coordinate evaluation so the evidence is undeniable.","summary":"Banning tobacco sales to anyone born after a set year, as the UK Tobacco and Vapes Bill does with a rising age of sale, could end smoking within a generation, so this idea forms an international consortium of adopting countries to pre-register outcome measures and evaluate the policy together. New Zealand repealed its version in 2024, so the evidence needs to be undeniable; age-of-sale laws such as Tobacco 21 in the US already reduce initiation, and a generational ban progressively removes the peer-supply loophole. Measures include smoking initiation by birth cohort, illicit market share and retail compliance. The test is a pre-registered synthetic-control evaluation. Being tested at scale, it addresses the bottleneck Prevention we already have is not deployed.","asOf":"2026-09-08","links":[{"label":"UK Tobacco and Vapes Bill (page moved; nearest live section)","url":"https://www.gov.uk/government/collections/"}],"tags":[],"related":[],"cancers":["nsclc"],"sections":["prevention"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A rising age of sale reduces smoking prevalence among the first affected birth cohorts by at least half relative to synthetic controls within five years.","rationale":"Age-of-sale laws already reduce initiation (Tobacco 21 in the US); a generational ban progressively removes the peer-supply loophole.","test":"Pre-registered synthetic-control evaluation.","maturity":"being-tested-at-scale","actor":"policy","cost":"small","horizonYears":6},{"id":"idea-fund-social-impact-bonds-prevention","kind":"idea","name":"Social impact bonds for cancer prevention, repaid from avoided treatment costs","aka":[],"tldr":"Investors would fund vaccination and screening campaigns up front and be repaid by health systems only if the campaigns hit verified targets, turning future savings into money for prevention now.","summary":"Outcome-based contracts in which private or philanthropic investors finance delivery programmes (HPV catch-up vaccination for adults up to 26 or 45, lung screening enrolment among smokers, hepatitis B and C test-and-treat, bowel screening uptake in low-participation areas) and the payer repays with a return only when independently verified coverage or diagnosis-stage targets are met. This shifts the risk of implementation failure from the health system to investors and aligns incentives on measured outcomes. Precedents exist in social care and in tuberculosis and HIV programmes in several countries.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Incentives reward me-too drugs and marginal gains): Upadhaya et al., PD1/PDL1 inhibitor clinical trial landscape (Nat Rev Drug Discov 2022)","url":"https://doi.org/10.1038/d41573-022-00030-4"}],"tags":[],"related":["idea-fund-prevention-moonshot"],"cancers":["cervical","nsclc","colorectal"],"sections":[],"technologies":["hpv-vaccine","radiology-ai-screening"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-incentive-misalignment","b-prevention-adoption"],"keyPapers":["paper-upadhaya-nat-rev-drug-discov"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Social impact bonds for cancer prevention achieve their coverage targets in at least two of the first three pilots at a cost per additional person covered no higher than standard grant-funded programmes, and payers repay with a return that is still below the projected downstream savings.","rationale":"Prevention is chronically under-funded because its savings accrue years later to different budgets; impact bonds move the money forward while keeping accountability on outcomes. Evaluations of health impact bonds show mixed cost-effectiveness but consistent outcome focus, so oncology pilots should be pre-registered with explicit comparisons.","test":"Run three bonds (HPV catch-up, lung screening, bowel screening) in different regions with independent verification and compare coverage and cost against matched regions using standard funding.","maturity":"speculative","actor":"payer","cost":"medium","horizonYears":5},{"id":"idea-reg-social-impact-bond-switching","kind":"idea","name":"Social impact bonds that fund biosimilar switching, repaid from payer savings","aka":[],"tldr":"Hospitals often lack the staff to switch patients to cheaper equivalent drugs. Private investors could fund the switching teams and be repaid by the health system from the money saved.","summary":"Switching programmes (pharmacists, patient information, prescribing system changes) return far more in drug savings than they cost, but compete for scarce operating budgets. A social impact bond raises private capital to fund the programme and repays investors, with a return, from verified savings measured against a pre-agreed baseline; the payer pays only if savings materialise. Social impact bonds have been used in social care and public health; oncology drug switching has an unusually measurable outcome.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Prices and value): Prasad, De Jesús & Mailankody, The high price of anticancer drugs: origins, implications, barriers, solutions (Nat Rev Clin Oncol 2017)","url":"https://doi.org/10.1038/nrclinonc.2017.31"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-drug-pricing","b-funding-allocation"],"keyPapers":["paper-prasad-nat-rev-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Bond-funded switching programmes achieve biosimilar and generic shares above 85% within a year and generate verified savings at least five times the programme cost, with investors repaid in full.","rationale":"The savings from switching are large, fast and measurable from claims data, which is exactly the profile that makes outcome-based financing work; the constraint is up-front capacity, which the bond supplies.","test":"Structure one bond covering ten hospitals for two new oncology biosimilar launches, with an independent evaluator verifying savings, and publish the returns and clinical safety data.","maturity":"speculative","actor":"philanthropy","cost":"medium","horizonYears":2},{"id":"idea-bio2-matrix-stiffness-prevention","kind":"idea","name":"Soften the tissue that new metastases need in order to grow","aka":[],"tldr":"Cancer cells need stiff, cross-linked tissue scaffolding to settle and grow in a new organ. Blocking the enzymes that build it may stop new colonies taking hold.","summary":"LOX and LOXL2 cross-link collagen to create the stiff matrix required for metastatic outgrowth, and hypoxia-driven LOX secretion prepares bone and lung niches. An anti-LOXL2 antibody failed in fibrosis and in advanced pancreatic cancer, but was never tested in the prevention setting where the biology predicts benefit and the target burden is small.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Metastasis is understood least and studied last): Dillekås et al., Are 90% of deaths from cancer caused by metastases? (Cancer Medicine 2019)","url":"https://doi.org/10.1002/cam4.2474"}],"tags":[],"related":[],"cancers":["pancreatic","breast-hr-positive"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["hif-vhl","emt"],"terms":["desmoplasia"],"trials":[],"people":["erik-sahai"],"bottlenecks":["b-metastasis-biology","b-negative-results"],"keyPapers":["paper-dillekas-cancer-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"LOX or LOXL2 inhibition given adjuvantly, when only micrometastatic disease is present, delays radiographic metastasis, while having no effect on established macroscopic disease.","rationale":"Matrix cross-linking is rate-limiting for outgrowth, not for the survival of an already vascularised lesion, which would explain why treatment trials failed. Early-intervention-only benefit has precedent in anti-fibrotic therapy for lung fibrosis.","test":"Test the setting-dependence in mice first: the identical agent in adjuvant versus established-metastasis designs. Only a large adjuvant-specific effect should trigger a human trial in high-risk resected disease.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":8},{"id":"idea-acc-solar-microgrids-for-cancer-units","kind":"idea","name":"Solar microgrids so radiotherapy, pathology and drug fridges never lose power","aka":[],"tldr":"Cancer units in poorer countries lose treatment days, spoil drugs and damage machines during power cuts. Solar panels with batteries sized for the cancer unit would remove that failure point.","summary":"Voltage instability and outages shorten linac component life, interrupt fractions, spoil temperature-sensitive drugs, and halt slide processing. Hospital solar microgrids with battery storage are now cost-competitive with diesel in most of Africa and South Asia. Designing the microgrid specifically for the cancer unit's load profile, with the linac on a conditioned circuit, is a bounded engineering project with quick payback.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Most of the world has almost no cancer care): WHO fact sheet, Cancer","url":"https://www.who.int/news-room/fact-sheets/detail/cancer"}],"tags":[],"related":[],"cancers":[],"sections":["radiation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-global-access"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Cancer units on a dedicated solar-plus-battery microgrid will cut power-related treatment interruptions by at least 80% and reduce linac component failures within two years compared with grid-plus-generator units.","rationale":"Off-grid solar transformed vaccine cold chains and rural clinics; the same approach applied to the highest-value equipment in a hospital has an obvious return.","test":"Install at five units, log outages, interruptions, fraction completions, and component replacements before and after, alongside fuel-cost savings.","maturity":"early-clinical","actor":"engineering","cost":"medium","horizonYears":2},{"id":"idea-reg-confirmatory-trial-escrow","kind":"idea","name":"Sponsors deposit the confirmatory trial budget in escrow at accelerated approval","aka":[],"tldr":"To get an early approval, a company would set aside the money for the follow-up trial up front, so the trial cannot be quietly abandoned.","summary":"Confirmatory trials for accelerated approvals are often delayed or redesigned in ways that reduce their chance of a clear answer. The proposal is a financial escrow: at approval the sponsor deposits the estimated cost of the pre-agreed confirmatory trial with an independent trustee. The funds are released against enrolment and reporting milestones; if the sponsor defaults, the trustee funds an academic cooperative group to complete the trial. This complements, rather than replaces, an automatic sunset.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Regulatory divergence between regions): FDA Oncology Center of Excellence, Project Orbis","url":"https://www.fda.gov/about-fda/oncology-center-excellence/project-orbis"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["accelerated-approval"],"trials":[],"people":[],"bottlenecks":["b-regulatory-fragmentation","b-incentive-misalignment"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Escrow-backed confirmatory trials reach their primary readout a median of 18 months sooner than historical confirmatory trials, and the proportion never reported falls to near zero.","rationale":"Escrow converts a soft regulatory commitment into a hard financial one and creates a funded route for independent completion when commercial interest wanes (for example after a competing product launches). Environmental remediation bonds work on the same logic.","test":"Legislative pilot in one region for new accelerated oncology approvals; compare time to confirmatory readout with concurrent non-escrow approvals elsewhere.","maturity":"speculative","actor":"policy","cost":"small","horizonYears":6},{"id":"idea-net-antagonist-ligands","kind":"idea","name":"SSTR antagonist radioligands to increase tumour dose","aka":[],"tldr":"Radioligand therapy for neuroendocrine tumours built on somatostatin receptor antagonists rather than the agonists used today: antagonists bind the receptor in every state and are not internalised, so they occupy several times more sites per cell and deliver more radiation per dose. The test is a randomised phase 2 against agonist lutetium therapy.","summary":"The idea is to build peptide receptor radionuclide therapy for neuroendocrine tumours on somatostatin receptor 2 antagonists rather than the agonists used today. Antagonists bind receptors in every conformational state and are not internalised, so they occupy several times more binding sites on each cell and deliver more radiation per dose. First-in-human studies of the antagonist 177Lu-satoreotide tetraxetan showed higher tumour uptake and dose than agonists, and early trials report responses in patients refractory to agonist PRRT. The hypothesis is higher response rates at an equivalent renal dose, including in tumours with low SSTR2 expression; the test is a randomised phase 2 of antagonist versus agonist 177Lu-PRRT in grade 1 to 2 gastroenteropancreatic NETs.","asOf":"2026-09-07","links":[{"label":"Reidy-Lagunes et al., Phase 1 trial of the SSTR antagonist radioligand 177Lu-satoreotide tetraxetan in neuroendocrine tumours (Clinical Cancer Research 2019)","url":"https://doi.org/10.1158/1078-0432.CCR-19-1026"}],"tags":[],"related":[],"cancers":["neuroendocrine"],"sections":[],"technologies":["prrt"],"targets":["sstr2"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["alphamedix-02","compete","nct04919226"],"people":[],"bottlenecks":[],"keyPapers":["paper-reidy-lagunes-clin-cancer-res"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Antagonist PRRT achieves higher response rates than agonist PRRT at equivalent renal dose, including in low-SSTR-expressing tumours.","rationale":"Antagonists bind receptors in all conformational states and are not internalised, increasing binding sites several-fold.","test":"Randomised phase 2 antagonist vs agonist 177Lu-PRRT in grade 1-2 GEP-NETs.","maturity":"early-clinical"},{"id":"idea-data-external-control-arm-standard","kind":"idea","name":"Standards for external control arms built from federated real-world data","aka":[],"tldr":"When a trial has no comparison group, the comparison is sometimes built from old patient records. Set rules for how that is done so the answer is not rigged.","summary":"External control arms from real-world or historical trial data are increasingly used in rare cancers and single-arm approvals, with inconsistent methods. The proposal defines standards: pre-specification before trial unblinding, construction from federated data with documented eligibility mapping, minimum covariate set, quantitative bias analysis and tipping-point sensitivity analyses, plus public deposition of the control cohort definition. Regulatory guidance (FDA 2023 draft on externally controlled trials) is the starting point.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Weak real-world evidence and registries): Gyawali, Hey & Kesselheim, Assessment of the clinical benefit of cancer drugs receiving accelerated approval (JAMA Intern Med 2019)","url":"https://doi.org/10.1001/jamainternmed.2019.0462"}],"tags":[],"related":[],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["real-world-evidence","basket-umbrella-platform"],"trials":[],"people":[],"bottlenecks":["b-real-world-evidence","b-trial-design","b-rare-cancers"],"keyPapers":["paper-gyawali-jama-intern-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Standardised external controls will reduce the discrepancy between single-arm effect estimates and subsequent randomised confirmation by half.","rationale":"Several single-arm approvals with historical controls were later contradicted by randomised trials; the failures trace to unmeasured confounding and cherry-picked comparators, both addressable by pre-specification and bias analysis.","test":"Reconstruct external controls under the standard for ten single-arm approvals that later had randomised confirmation; compare the standardised estimate with the randomised result.","maturity":"early-clinical","actor":"regulator","cost":"small","horizonYears":2},{"id":"idea-tr2-spatial-biomarker-standards","kind":"idea","name":"Standards for spatial and multiplex tissue biomarkers before they reach the clinic","aka":[],"tldr":"New microscopes can measure dozens of proteins at once and map where immune cells sit in a tumour. These readouts could predict immunotherapy response, but every lab does it differently.","summary":"Multiplex immunofluorescence and spatial transcriptomics generate spatial biomarkers (immune cell distances, niches, tertiary lymphoid structures) with strong retrospective association to immunotherapy outcome. Platforms, panels, segmentation and metrics are not standardised, so no spatial biomarker has reached clinical validation. A consortium defining minimal reporting, reference tissue, shared segmentation benchmarks and a core panel would let spatial biomarkers be compared across studies and taken into prospective trials.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Biomarkers are not validated or standardised): Fernandez et al., Examination of low ERBB2 protein expression in breast cancer tissue (JAMA Oncology 2022)","url":"https://doi.org/10.1001/jamaoncol.2021.7239"}],"tags":[],"related":["10x-genomics"],"cancers":[],"sections":[],"technologies":["single-cell-spatial","digital-pathology-ai"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["tils","cold-vs-hot"],"trials":[],"people":[],"bottlenecks":["b-biomarker-validation","b-immunotherapy-response"],"keyPapers":["paper-fernandez-jama-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A standardised spatial immune score will predict PD-1 blockade response with an area under the curve above 0.75 across two independent cohorts run on different platforms, exceeding PD-L1 IHC.","rationale":"Multi-institutional meta-analyses find spatial features outperform PD-L1 in retrospective data; lack of standards, not lack of signal, blocks translation.","test":"Run a multi-site ring study on the same tissue blocks across platforms; define the reproducible feature set; validate prospectively in an immunotherapy trial.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":4},{"id":"idea-acc-reflex-biomarker-panels-by-tumour","kind":"idea","name":"Standing reflex biomarker panels per tumour type, run without an oncologist's order","aka":[],"tldr":"For each cancer type, agree the set of stains and tests that are always needed, and have the lab run them automatically on diagnosis rather than waiting for someone to ask.","summary":"Beyond genomic profiling, predictive tests such as PD-L1, mismatch repair, HER2 in gastric and colorectal cancer, and HPV/p16 in oropharynx are ordered inconsistently, delaying or denying effective therapy. A national or hospital-level reflex protocol per tumour type, maintained against current guidelines, would make testing complete and timely. Reflex mismatch-repair testing in colorectal cancer for Lynch syndrome is an established precedent.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Fragmented care and guideline gaps): Hanna et al., Mortality due to cancer treatment delay: systematic review and meta-analysis (BMJ 2020)","url":"https://doi.org/10.1136/bmj.m4087"}],"tags":[],"related":["idea-acc-reflex-genomic-profiling-at-diagnosis"],"cancers":["colorectal","gastric","head-and-neck","nsclc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["msi","cps"],"trials":[],"people":[],"bottlenecks":["b-care-fragmentation","b-biomarker-validation"],"keyPapers":["paper-hanna-bmj"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Reflex panels will raise completeness of guideline-required predictive biomarkers at first oncology visit to above 95% and cut time from diagnosis to first-line treatment decision by at least a week.","rationale":"Testing that depends on an individual clinician remembering to order it will always be incomplete; making it a laboratory default removes the failure mode.","test":"Implement reflex panels in a regional laboratory network and audit completeness, turnaround, and downstream therapy use before and after.","maturity":"being-tested-at-scale","actor":"clinic","cost":"small","horizonYears":1},{"id":"idea-tr1-start-low-titrate-up-oral-agents","kind":"idea","name":"Start low and step up: individualised titration of oral cancer drugs, randomised","aka":[],"tldr":"Instead of starting everyone on the full dose and cutting back after side effects, start lower and increase in patients who tolerate it. This keeps more people on treatment and is how blood-pressure drugs are given.","summary":"Randomised comparisons of standard full-dose start versus a step-up schedule (starting at 50-70 percent of label dose, escalating at cycle 2-3 in the absence of toxicity) for oral agents with high early discontinuation rates (some PARP inhibitors, multi-kinase inhibitors, CDK4/6 inhibitors, PI3K/AKT inhibitors). Niraparib's individualised starting dose by weight and platelet count is a precedent that improved tolerability without loss of efficacy.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Wrong doses): FDA Oncology Center of Excellence, Project Optimus","url":"https://www.fda.gov/about-fda/oncology-center-excellence/project-optimus"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["parp-inhibitor","cdk46-inhibitor"],"targets":[],"drugs":["niraparib","abemaciclib","capivasertib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-dose-optimisation","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Step-up dosing will reduce early discontinuation and grade 3+ toxicity in the first three cycles by at least a third, with non-inferior PFS, for agents with exposure-driven early toxicity.","rationale":"Early toxicity drives discontinuation before benefit can accrue; many patients who reduce dose after toxicity do as well as those who do not, suggesting the starting dose is too high for a subset.","test":"Randomised phase 3 non-inferiority trials of step-up versus full-dose starts for two oral agents with documented high early discontinuation, powered for PFS with discontinuation as key secondary.","maturity":"early-clinical","actor":"industry","cost":"medium","horizonYears":3},{"id":"idea-bio1-translation-dependency-myc","kind":"idea","name":"Starve MYC-driven tumours by blocking protein production machinery","aka":[],"tldr":"Cancers driven by MYC need to make proteins at an unusually fast rate. Slowing the cell's protein factory hits them harder than it hits normal cells.","summary":"MYC amplification imposes dependence on cap-dependent translation, ribosome biogenesis and eIF4A/eIF4E activity. Selective eIF4A inhibitors (for example zotatifin) and RNA polymerase I inhibitors have entered clinical trials. Rather than treating these as broad cytotoxics, the proposal is to select patients by MYC amplification or a translation-dependency signature, which has not been done systematically.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The undruggable drivers): Dang et al., Drugging the 'undruggable' cancer targets (Nature Reviews Cancer 2017)","url":"https://doi.org/10.1038/nrc.2017.36"}],"tags":[],"related":[],"cancers":["sclc","tnbc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["oncogene-addiction"],"trials":[],"people":[],"bottlenecks":["b-undruggable-targets","b-biomarker-validation"],"keyPapers":["paper-dang-nat-rev-cancer"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Response to eIF4A or ribosome biogenesis inhibition is concentrated in tumours with MYC amplification or a high translation-dependency signature, with a response rate at least three times that of unselected patients.","rationale":"Blocking translation is an indirect route to MYC that requires no MYC binder; the dependency is well supported in models, but trials to date have largely been unselected, which is a common reason such drugs fail.","test":"Biomarker-stratified phase 2 with pre-specified MYC-amplified and signature-high cohorts, powered to compare response rates between strata.","maturity":"early-clinical","actor":"industry","cost":"medium","horizonYears":4},{"id":"idea-bio1-persister-metabolic-vulnerability","kind":"idea","name":"Starve the survivors: target the energy pathway drug-tolerant cells switch to","aka":[],"tldr":"Cells that survive treatment often change how they make energy, relying on burning fat rather than sugar. Blocking that switch might finish them off.","summary":"Drug-tolerant persisters and residual disease cells show increased oxidative phosphorylation and fatty acid oxidation dependence in melanoma, lung and leukaemia models. OXPHOS and fatty acid oxidation inhibitors have entered early clinical testing, with tolerability as the main issue. The proposal is intermittent, response-triggered administration at the point of maximal response rather than continuous use in bulk disease.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Acquired resistance to every therapy): Soria et al., Osimertinib in untreated EGFR-mutated NSCLC (FLAURA, NEJM 2018)","url":"https://doi.org/10.1056/NEJMoa1713137"}],"tags":[],"related":[],"cancers":["melanoma","aml"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["mrd","resistance"],"trials":[],"people":[],"bottlenecks":["b-resistance","b-dormancy-mrd"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Metabolic inhibition applied at maximal response reduces measurable residual disease more than continuing targeted therapy alone, without the toxicity seen with continuous dosing.","rationale":"Metabolic state, unlike genotype, is shared across many persister populations, so the approach could apply across drivers; the failures of OXPHOS inhibitors to date have been in unselected bulk disease.","test":"Preclinical timing study comparing continuous versus nadir-triggered metabolic inhibition, then a phase 1b in patients in deep response with ctDNA as the pharmacodynamic endpoint.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":6},{"id":"idea-prev-gastric-serology-migrant-screening","kind":"idea","name":"Stomach cancer serology screening for high-risk migrant communities in low-incidence countries","aka":[],"tldr":"People who grew up in East Asia, Eastern Europe or Latin America keep a high stomach cancer risk after migrating. Cheap blood tests could select who needs an endoscopy.","summary":"Pepsinogen I/II ratio plus H. pylori serology (the ABC method) stratifies gastric cancer risk in Japan. Western countries do not screen because average incidence is low, but first-generation migrants from high-incidence regions carry two- to five-fold risk. Propose targeted serological screening with endoscopy for high-risk groups.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The hardest cancers are found late): Crosby et al., Early detection of cancer (Science 2022)","url":"https://doi.org/10.1126/science.aay9040"}],"tags":[],"related":[],"cancers":["gastric"],"sections":["early-detection"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-early-detection","b-trial-diversity"],"keyPapers":["paper-crosby-science"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Serology-directed endoscopy in first-generation migrants from high-incidence regions aged 50 and over yields early gastric cancer or high-grade dysplasia in at least 1% of endoscopies, comparable to Japanese and Korean programmes.","rationale":"Risk follows birthplace and childhood H. pylori acquisition; the serology is cheap and validated.","test":"Pilot in 5,000 participants in a large migrant community (e.g. California, London); yield and cost per early cancer.","maturity":"speculative","actor":"clinic","cost":"small","horizonYears":4},{"id":"idea-prev-thyroid-no-screening-no-small-biopsy","kind":"idea","name":"Stop biopsying small thyroid nodules and never screen the thyroid","aka":[],"tldr":"South Korea's thyroid cancer rate rose 15-fold after ultrasound screening, with no fall in deaths. A firm rule not to biopsy nodules under 1 cm, and not to screen, would prevent this harm elsewhere.","summary":"Korean thyroid overdiagnosis is the clearest natural experiment in the field, and incidence fell after the 2014 public debate without any mortality change. Guidelines already discourage biopsy of sub-centimetre nodules but practice varies. Propose national policy: no ultrasound thyroid screening, mandatory adherence to size thresholds, and public reporting of the thyroid cancer incidence-to-mortality ratio as a harm indicator.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Overdiagnosis and false alarms): Welch & Black, Overdiagnosis in cancer (JNCI 2010)","url":"https://doi.org/10.1093/jnci/djq099"}],"tags":[],"related":[],"cancers":["thyroid"],"sections":["early-detection"],"technologies":["ultrasound"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-overdiagnosis"],"keyPapers":["paper-welch-j-natl-cancer-inst"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Policy adoption reduces thyroid cancer incidence by at least 30% within five years with no change in thyroid cancer mortality.","rationale":"Korea showed reversibility: incidence fell rapidly once biopsy thresholds were enforced.","test":"Interrupted time-series in adopting regions versus controls.","maturity":"being-tested-at-scale","actor":"policy","cost":"small","horizonYears":4},{"id":"idea-bio2-cns-cohort-mandate","kind":"idea","name":"Stop excluding brain metastases from cancer trials","aka":[],"tldr":"One in five people with advanced cancer has brain spread, yet most trials refuse them. Requiring brain cohorts would give those patients evidence instead of guesswork.","summary":"Brain metastasis exclusion criteria persist by habit, and regulators and professional bodies have issued guidance encouraging inclusion of patients with stable treated brain metastases. Making a CNS cohort with CNS-specific response endpoints a default expectation for registrational trials in CNS-tropic cancers, unless justified otherwise, would generate labelled intracranial data rather than post-approval retrospectives.","asOf":"2026-09-08","links":[{"label":"ASCO-Friends eligibility criteria work","url":"https://www.asco.org"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["asco","esmo"],"pathways":[],"terms":["her2-brain-metastases"],"trials":["her2climb","alina"],"people":[],"bottlenecks":["b-brain-delivery","b-trial-enrolment","b-trial-design"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A default-inclusion policy raises the proportion of new oncology approvals with intracranial activity data in the label from a minority to over half within five years, without slowing accrual.","rationale":"Inclusion of patients with treated brain metastases has been feasible where sponsors have tried it, and the resulting intracranial data changed practice in HER2-positive breast cancer and ALK-positive lung cancer. The barrier is convention and risk aversion, not science.","test":"Audit exclusion criteria in the last 200 registrational oncology protocols, publish the rate, then have one regulator or cooperative group adopt default CNS cohorts for CNS-tropic diseases and measure accrual, safety and labelling outcomes.","maturity":"speculative","actor":"regulator","cost":"small","horizonYears":4},{"id":"idea-tr1-prior-cancer-hiv-hepatitis-inclusion","kind":"idea","name":"Stop excluding people with a prior cancer, controlled HIV, or treated hepatitis","aka":[],"tldr":"Having had another cancer years ago, or living with controlled HIV or treated hepatitis, still keeps patients out of trials for no scientific reason. Condition-specific rules, as FDA guidance recommended in 2020, would replace blanket bans and widen access in communities where these conditions are more common.","summary":"Protocols would replace blanket exclusions with condition-specific rules: prior malignancy allowed unless it is likely to interfere with the endpoint; HIV allowed if on effective antiretrovirals with adequate CD4 count; hepatitis B and C allowed if suppressed or cured. The FDA issued a guidance to this effect in 2020; adoption is incomplete and monitoring of adoption is absent.","asOf":"2026-09-08","links":[{"label":"FDA: Eligibility Criteria: Patients with HIV, Hepatitis B or Hepatitis C","url":"https://www.fda.gov/regulatory-information/search-fda-guidance-documents/cancer-clinical-trial-eligibility-criteria-patients-hiv-hepatitis-b-virus-or-hepatitis-c-virus"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["nci","asco"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-enrolment","b-trial-diversity"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Trials adopting these criteria will increase enrolment of Black and Hispanic participants in the US and of participants in high-HIV-prevalence countries, with no detectable difference in efficacy estimates or serious adverse events among the newly eligible.","rationale":"Cancer survivors are a growing population and often have the same disease biology; HIV on modern therapy does not alter most drug pharmacology or checkpoint-inhibitor safety in observational series; hepatitis exclusion is largely a legacy of hepatotoxicity concerns that can be handled by monitoring.","test":"Audit new industry phase 3 protocols each year for these exclusions, publish a scorecard, and compare outcomes of the newly eligible subgroup in trials that include them.","maturity":"early-clinical","actor":"industry","cost":"small","horizonYears":2},{"id":"idea-tr1-aggressive-futility-boundaries","kind":"idea","name":"Stop failing trials earlier with pre-registered aggressive futility rules","aka":[],"tldr":"Large phase 3 trials often continue for years after interim data show the drug is unlikely to work. Pre-registering futility boundaries at 30 to 50 percent of the information, judged by independent committees and reported publicly, would stop them earlier, sparing patients and freeing money for better ideas.","summary":"Phase 3 protocols include non-binding but pre-registered futility boundaries at 30-50 percent information (predictive probability of success below a threshold), evaluated by independent monitoring committees, with public reporting of the interim decision. Sponsors commit to the rule in the registry entry, reducing the temptation to continue for commercial reasons.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Trial design, endpoints and cost): Davis et al., Availability of evidence of benefits on survival and quality of life of cancer drugs approved by EMA 2009-13 (BMJ 2017)","url":"https://doi.org/10.1136/bmj.j4530"}],"tags":[],"related":["clinicaltrials-gov"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-design","b-negative-results","b-funding-allocation"],"keyPapers":["paper-davis-bmj"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Trials with pre-registered aggressive futility rules will stop negative studies a median of 12 months earlier and expose 30 percent fewer patients to ineffective experimental arms, with a negligible increase in falsely abandoned effective drugs.","rationale":"Retrospective analyses of negative phase 3 trials show most would have met conventional futility criteria at interim, yet sponsors often lack pre-specified rules or set them conservatively.","test":"Simulate aggressive futility rules on completed negative phase 3 trials with interim data available and quantify time and patients saved versus false stops of positive trials.","maturity":"speculative","actor":"industry","cost":"small","horizonYears":2},{"id":"idea-tr1-include-pregnancy-capable-people-sensibly","kind":"idea","name":"Stop over-excluding people who could become pregnant; study pregnancy exposure","aka":[],"tldr":"Trials often impose heavy contraception rules and exclude anyone pregnant or breastfeeding, even when the drug is unlikely to be harmful. Sensible, evidence-based rules and pregnancy registries would include more young women and produce data they currently lack.","summary":"Contraception requirements are set from the drug's actual reproductive toxicology rather than a blanket demand for two contraceptive methods; breastfeeding exclusion is replaced by lactation PK studies where feasible; and pregnancy exposure registries are funded for oncology drugs so that the inevitable exposures generate data. Adolescent and young adult women are disproportionately affected by current rules.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Trials do not represent the people who get cancer): Loree et al., Disparity of race reporting and representation in trials leading to cancer drug approvals (JAMA Oncology 2019)","url":"https://doi.org/10.1001/jamaoncol.2019.1870"}],"tags":[],"related":[],"cancers":["tnbc","cervical","hodgkin-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-diversity","b-trial-enrolment"],"keyPapers":["paper-loree-jama-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Evidence-based reproductive criteria will increase enrolment of women under 45 without increasing exposed pregnancies, and lactation and pregnancy registries will generate label information for most oncology drugs within a decade.","rationale":"Cancer in pregnancy and in lactating women is treated on almost no data; young women decline trials because of contraception burden; other therapeutic areas have moved to risk-based reproductive criteria.","test":"Audit contraception criteria against reproductive toxicology for approved agents; pilot risk-based criteria in one cooperative group and measure enrolment of women under 45 and exposed pregnancies.","maturity":"speculative","actor":"regulator","cost":"small","horizonYears":3},{"id":"idea-prev-barrett-surveillance-deescalation","kind":"idea","name":"Stop routine endoscopies for non-dysplastic Barrett's oesophagus","aka":[],"tldr":"People with Barrett's oesophagus without dysplasia have endoscopies every few years, but the BOSS trial found no survival benefit. Redirecting effort to those with dysplasia would save harm and cost.","summary":"BOSS (UK) randomised surveillance versus at-need endoscopy and found no mortality benefit. Propose guideline change to stop routine surveillance for non-dysplastic short-segment Barrett's, replacing it with capsule sponge or biomarker (p53, TFF3) risk stratification to select the minority for surveillance.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Overdiagnosis and false alarms): Welch & Black, Overdiagnosis in cancer (JNCI 2010)","url":"https://doi.org/10.1093/jnci/djq099"}],"tags":[],"related":[],"cancers":["esophageal"],"sections":["early-detection"],"technologies":[],"targets":["tp53"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-overdiagnosis"],"keyPapers":["paper-welch-j-natl-cancer-inst"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Biomarker-stratified surveillance reduces endoscopies by at least 60% with no increase in oesophageal adenocarcinoma mortality.","rationale":"Randomised evidence of no benefit; p53 immunohistochemistry identifies the progressors.","test":"Implement and monitor via registry; embedded RCT of biomarker-stratified surveillance.","maturity":"early-clinical","actor":"policy","cost":"small","horizonYears":4},{"id":"idea-prev-screening-stop-by-life-expectancy","kind":"idea","name":"Stop screening by life expectancy, not birthday, with a tool in the record","aka":[],"tldr":"Screening someone unlikely to live ten years causes harm without benefit. A life-expectancy estimate in the medical record could stop invitations and prompt a conversation.","summary":"Screening someone unlikely to live ten years causes harm without benefit, while healthy older adults are excluded by birthday, so this idea embeds an ePrognosis-type life-expectancy tool in the medical record to gate screening invitations and prompt a conversation. Individualised cessation is guideline-endorsed but not implemented, and deprescribing frameworks show it can be done. The aim is less screening in people with under ten years of life expectancy and more in healthy older adults, with patient acceptance measured. The test is a cluster RCT in primary care with over-screening and under-screening as endpoints. At early-clinical maturity it addresses the bottlenecks Overdiagnosis and false alarms and Older and multimorbid patients are excluded and undertreated.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Overdiagnosis and false alarms): Welch & Black, Overdiagnosis in cancer (JNCI 2010)","url":"https://doi.org/10.1093/jnci/djq099"}],"tags":[],"related":[],"cancers":[],"sections":["early-detection"],"technologies":["geriatric-assessment"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-overdiagnosis","b-aging-comorbidity"],"keyPapers":["paper-welch-j-natl-cancer-inst"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Life-expectancy gating reduces screening in people with under ten years' expectancy by at least 30% and increases it in healthy older adults, with patient acceptance of at least 80%.","rationale":"Individualised cessation is guideline-endorsed but not implemented; deprescribing frameworks show it can be done.","test":"Run a cluster RCT in primary care.","maturity":"early-clinical","actor":"clinic","cost":"small","horizonYears":3},{"id":"idea-prev-ipmn-surveillance-stop-rule","kind":"idea","name":"Stop watching stable low-risk pancreatic cysts after five years","aka":[],"tldr":"Small pancreatic cysts turn up on abdominal scans and are then followed for life. Low-risk cysts under 2 cm that are unchanged at five years rarely turn to cancer in Japanese and US cohorts, so a randomised trial of stopping surveillance would test whether years of scans can be spared.","summary":"Low-risk branch-duct IPMN under 2 cm that is stable at five years has low malignancy rates in Japanese and US cohorts, but guidelines diverge. Propose a randomised trial of surveillance cessation versus continued surveillance for stable low-risk cysts, with pancreatic cancer incidence and imaging burden as endpoints.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Overdiagnosis and false alarms): Welch & Black, Overdiagnosis in cancer (JNCI 2010)","url":"https://doi.org/10.1093/jnci/djq099"}],"tags":[],"related":[],"cancers":["pancreatic","ipmn-cystic-precursors"],"sections":["early-detection","imaging"],"technologies":["mri"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-overdiagnosis"],"keyPapers":["paper-welch-j-natl-cancer-inst"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Cessation after five years of stability results in pancreatic cancer incidence under 1% over five further years, non-inferior to continued surveillance.","rationale":"Lifelong surveillance carries cost and anxiety; event rates in stable cysts are low.","test":"2,000-patient multicentre RCT.","maturity":"speculative","actor":"clinic","cost":"medium","horizonYears":6},{"id":"idea-prev-deferred-disclosure-newborn-genomes","kind":"idea","name":"Store adult-onset cancer gene results from newborn genomes and disclose at 18","aka":[],"tldr":"Newborn sequencing programmes exclude adult cancer genes because babies cannot consent. Storing those results and offering them at 18 would preserve choice and give a lifetime of prevention.","summary":"Newborn sequencing programmes such as Genomics England's Generation Study exclude adult-onset cancer genes because babies cannot consent, so this idea sequesters actionable adult-onset variants in BRCA and Lynch genes and offers them for disclosure at 18 with counselling. This avoids re-sequencing, respects autonomy and captures carriers before cancer develops, so that they enter surveillance far earlier than through current diagnosis routes. The test is a pilot consent and disclosure protocol in an existing newborn genome cohort. Speculative in maturity, it addresses the bottleneck Inherited risk is mostly unidentified and links to germline testing and whole-genome sequencing.","asOf":"2026-09-08","links":[{"label":"Genomics England","url":"https://www.genomicsengland.co.uk"}],"tags":[],"related":[],"cancers":[],"sections":["prevention"],"technologies":["germline-testing","wes-wgs"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-hereditary-risk"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"At least 70% of participants opt in to deferred disclosure at 18, and carriers enter surveillance a median 15 years earlier than through current diagnosis routes.","rationale":"Avoids re-sequencing, respects autonomy, and captures carriers before cancer develops.","test":"Pilot consent and disclosure protocol in an existing newborn genome cohort.","maturity":"speculative","actor":"policy","cost":"medium","horizonYears":10},{"id":"idea-reg-realtime-streaming-submission","kind":"idea","name":"Stream trial data to regulators as it accrues; review starts at last patient visit","aka":[],"tldr":"Instead of waiting months for a company to package trial results, regulators would see the data flow in during the trial and could decide within weeks of it ending.","summary":"FDA's Real-Time Oncology Review allows early submission of top-line data and datasets; this proposal goes further, with a standardised, validated data pipeline (CDISC SDTM/ADaM generated continuously from the sponsor's EDC) delivered to a shared regulator environment under blinded access controls during the trial. At database lock the regulator already holds cleaned data; the assessment starts immediately and the label negotiation is the only serial step.","asOf":"2026-09-08","links":[{"label":"FDA Real-Time Oncology Review","url":"https://www.fda.gov/about-fda/oncology-center-excellence/real-time-oncology-review"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-regulatory-fragmentation","b-data-silos"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Streaming submission cuts the interval from database lock to approval decision for positive pivotal oncology trials to under 60 days, compared with a current median of roughly 8-12 months including dossier preparation.","rationale":"Most of the time between a positive readout and approval is dossier assembly and sequential question rounds, not scientific deliberation. RTOR has already shown that approvals can follow readouts by weeks when data arrive early.","test":"Pilot with five sponsors on five phase 3 trials with streaming submission to FDA and EMA jointly; measure lock-to-decision time and the number of information requests against matched RTOR and conventional reviews.","maturity":"early-clinical","actor":"regulator","cost":"medium","horizonYears":3},{"id":"idea-bio2-platelet-cloak-aspirin-mrd","kind":"idea","name":"Strip the platelet coat off travelling tumour cells in ctDNA-positive patients","aka":[],"tldr":"Cancer cells in the blood wrap themselves in platelets as camouflage. Aspirin may remove that cloak, and it is cheapest to test in the patients at highest risk of relapse.","summary":"Platelet cloaking shields circulating tumour cells from natural killer cells and shear stress and supplies TGF-beta that drives epithelial-mesenchymal transition. Aspirin has adjuvant signals in PIK3CA-pathway-mutant colorectal cancer and is being tested at scale in unselected populations, but no trial has enriched for molecular residual disease, where the event rate is high and the biology is precisely platelet-tumour cell interaction.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Metastasis is understood least and studied last): Dillekås et al., Are 90% of deaths from cancer caused by metastases? (Cancer Medicine 2019)","url":"https://doi.org/10.1002/cam4.2474"}],"tags":[],"related":[],"cancers":["colorectal","breast-hr-positive"],"sections":[],"technologies":["mrd-testing","liquid-biopsy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["emt"],"terms":[],"trials":["dynamic","circulate-japan"],"people":[],"bottlenecks":["b-metastasis-biology","b-dormancy-mrd","b-generic-repurposing"],"keyPapers":["paper-dillekas-cancer-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"In patients who are ctDNA-positive after curative surgery, aspirin added to standard care produces higher ctDNA clearance at six months than standard care alone.","rationale":"An MRD-enriched design turns a small absolute effect in an unselected population into a testable large relative effect in a small trial, and gives a molecular endpoint that reads out in months rather than years.","test":"A 200-patient randomised trial inside an existing MRD platform in colorectal or breast cancer, with six-month ctDNA clearance as primary endpoint and platelet-CTC imaging as a mechanistic substudy.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":5},{"id":"idea-acc-structured-deprescribing-at-diagnosis","kind":"idea","name":"Structured deprescribing review at cancer diagnosis and again at transition to palliative care","aka":[],"tldr":"Older cancer patients often take ten or more medicines, some of which no longer help and may interact with cancer treatment. A pharmacist review to stop unnecessary ones, at diagnosis and when goals change, would reduce harm.","summary":"Polypharmacy is common in older patients with cancer and is associated with toxicity, falls, and hospitalisation. Preventive medicines with long time-to-benefit (statins in limited prognosis, tight glycaemic control, bisphosphonates for osteoporosis in the last year of life) can be stopped. Evidence-based deprescribing algorithms exist for many drug classes. A protocolised pharmacist-led review at two defined points would apply them systematically.","asOf":"2026-09-08","links":[{"label":"Deprescribing.org algorithms","url":"https://deprescribing.org/"}],"tags":[],"related":["idea-acc-oncology-pharmacist-prescribing"],"cancers":[],"sections":["supportive-care"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-aging-comorbidity","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Structured deprescribing will reduce the mean number of medicines by at least two per patient and reduce adverse drug events and falls by at least 20%, without increasing symptom burden.","rationale":"Deprescribing trials in geriatrics show safety and modest benefit; oncology adds a clear prognostic frame that makes stopping easier to justify.","test":"A randomised trial in 600 patients over 70 with adverse drug events, falls, quality of life, and medicine counts as endpoints.","maturity":"early-clinical","actor":"clinic","cost":"small","horizonYears":2},{"id":"idea-exercise-as-adjuvant","kind":"idea","name":"Structured exercise prescribed like a drug in all curative-intent cancer care","aka":[],"tldr":"The CHALLENGE trial showed a supervised exercise programme improves survival in colon cancer. Extend it to breast, prostate, and lung cancer with the same rigour.","summary":"The CHALLENGE trial showed that a supervised exercise programme improves outcomes in colon cancer, and this idea extends the same rigour to breast, prostate and lung cancer, prescribing structured exercise like a drug in all curative-intent care. A three-year programme after curative treatment is expected to improve disease-free survival through insulin and IGF reduction, lower inflammation and immune surveillance. Level-1 evidence now exists, so implementation is the barrier: reimbursement, workforce and adherence. The test is CHALLENGE-design trials in TNBC and prostate cancer with health-economic analysis and digital delivery arms. Being tested at scale, it addresses the bottlenecks Cachexia, toxicity and the limits of the patient and Survivorship and late effects are neglected.","asOf":"2026-09-04","links":[{"label":"CHALLENGE: structured exercise after adjuvant chemotherapy for colon cancer (NEJM 2025)","url":"https://doi.org/10.1056/NEJMoa2502760"}],"tags":[],"related":[],"cancers":["colorectal","tnbc","prostate"],"sections":[],"technologies":["exercise-oncology"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A 3-year structured exercise programme after curative treatment improves iDFS in TNBC (and other cancers) with effect sizes comparable to some adjuvant drugs.","rationale":"Mechanisms include insulin/IGF reduction, inflammation, and immune surveillance; effect size in CHALLENGE (DFS HR 0.72) rivals drugs.","test":"Run CHALLENGE-design trials in TNBC and prostate cancer with health-economic analysis and digital delivery arms.","maturity":"being-tested-at-scale"},{"id":"idea-acc-district-surgeon-oncology-mentorship","kind":"idea","name":"Structured mentorship so district general surgeons perform common cancer operations safely","aka":[],"tldr":"Surgery cures more cancers than any other treatment, but most district hospitals refer everything to a distant centre. Train and mentor general surgeons to do common cancer operations well, with specialists checking results.","summary":"Mastectomy, colectomy, gastrectomy, and hysterectomy for cancer are within the technical reach of general surgeons in district hospitals if they are trained in oncological principles (margins, lymph node handling, staging documentation) and mentored through their first cases, with pathology review and outcome audit. Surgical mentorship networks and low-cost simulation exist in general surgery; the oncology-specific layer is missing.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Not enough oncologists, nurses, pathologists, physicists): Yang et al., Projected supply of and demand for oncologists and radiation oncologists through 2025 (JOP 2014)","url":"https://doi.org/10.1200/JOP.2013.001319"}],"tags":[],"related":[],"cancers":["breast-hr-positive","colorectal","gastric"],"sections":["surgery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-workforce","b-global-access","b-surgery-radiation-innovation"],"keyPapers":["paper-yang-j-oncol-pract"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Mentored district surgeons will achieve margin-negative rates and 30-day morbidity comparable to regional cancer centres for a defined list of operations, while reducing patient travel and waiting time by more than half.","rationale":"The Lancet Commission on Global Surgery and the evidence from surgical task-sharing show that structured supervision maintains quality; cancer surgery volume in LMICs is the largest unfilled cure opportunity.","test":"A prospective audit of 1,000 operations across 20 mentored district hospitals against regional-centre benchmarks, with pathology-verified margins and nodal yield.","maturity":"early-clinical","actor":"clinic","cost":"medium","horizonYears":3},{"id":"idea-data-structured-radiology-response","kind":"idea","name":"Structured, coded radiology reports for cancer response instead of free text","aka":[],"tldr":"Radiologists would record tumour measurements and response in tick-box, coded form rather than prose, so progression is machine-readable across every scan.","summary":"Response assessment (RECIST, PERCIST) is documented in free text that machines cannot reliably parse. Structured reporting templates with coded lesion measurements (RSNA RadReport, DICOM SR) and a response field would make progression a first-class data element for registries and RWE. The proposal mandates structured oncology follow-up reporting in publicly funded imaging and funds template integration in reporting software.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Data silos): AACR Project GENIE","url":"https://www.aacr.org/professionals/research/aacr-project-genie/"}],"tags":[],"related":[],"cancers":[],"sections":["ai-computation","imaging"],"technologies":["ct","mri","pet-ct"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["recist","pfs"],"trials":[],"people":[],"bottlenecks":["b-data-silos","b-real-world-evidence"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Structured response reporting will raise machine-derivable progression dates from under 30 percent to over 90 percent of follow-up scans and make real-world PFS as reliable as trial PFS.","rationale":"Structured reporting has improved completeness in prostate MRI (PI-RADS) and lung nodules (Lung-RADS); response assessment is the missing oncology template.","test":"Deploy a structured response template at three centres; compare agreement of derived progression dates with trial-style central review in 500 patients against free-text NLP extraction.","maturity":"early-clinical","actor":"clinic","cost":"small","horizonYears":2},{"id":"idea-data-standard-of-care-change-alerts","kind":"idea","name":"Subscribable alerts when the standard of care changes for a patient's situation","aka":[],"tldr":"Doctors and patients could subscribe to a specific cancer, stage and biomarker and be told, with sources, the moment the recommended treatment changes for that situation.","summary":"Practice changes reach clinicians and patients through conferences, news and word of mouth. With computable guidelines and structured trial results, a change in recommendation for a defined population (for example, HER2-low metastatic breast cancer, second line) can be detected and pushed as a structured alert with the evidence and plain-language summary, to clinicians via the EHR and to patients via apps, with a flag for patients who may be affected.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Knowledge reaches practice too slowly): Morris, Wooding & Grant, The answer is 17 years, what is the question (JRSM 2011)","url":"https://doi.org/10.1258/jrsm.2011.110180"}],"tags":[],"related":["idea-data-computable-living-guidelines","idea-data-plain-language-summary-mandate"],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-knowledge-diffusion","b-patient-voice"],"keyPapers":["paper-morris-j-r-soc-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Situation-specific alerts will shorten the time between a practice-changing result and its application to eligible patients, especially in community settings.","rationale":"Personalised, timely, actionable messages outperform broadcast dissemination in behaviour change research; oncology has never had the structured backbone to send them.","test":"Offer alerts to clinicians in a network for one year covering ten practice changes; compare uptake in their eligible patients with non-subscribers via structured data.","maturity":"speculative","actor":"engineering","cost":"small","horizonYears":2},{"id":"idea-reg-io-subscription-national","kind":"idea","name":"Subscription pricing for checkpoint inhibitors: fixed national fee, unlimited use","aka":[],"tldr":"Instead of paying per dose, a country would pay a fixed annual fee and treat every eligible patient with immunotherapy. This has worked for hepatitis C drugs and antibiotics.","summary":"Louisiana and Australia bought hepatitis C antivirals under subscription ('Netflix') models that delinked revenue from volume, and NHS England pays fixed annual subscriptions for two antibiotics. Checkpoint inhibitors are used across dozens of indications, are volume-limited in most middle-income countries by per-dose price, and have low marginal manufacturing cost. The proposal is a national subscription contract: a fixed annual payment for unlimited pembrolizumab or nivolumab (or a biosimilar once available) in all approved indications, with the manufacturer's incentive shifted to supporting diagnosis and appropriate use.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Prices and value): Prasad, De Jesús & Mailankody, The high price of anticancer drugs: origins, implications, barriers, solutions (Nat Rev Clin Oncol 2017)","url":"https://doi.org/10.1038/nrclinonc.2017.31"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":[],"drugs":["pembrolizumab","nivolumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-drug-pricing","b-global-access"],"keyPapers":["paper-prasad-nat-rev-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"In a subscribing middle-income country the number of patients treated with checkpoint inhibitors rises at least threefold at total spend no higher than the prior year, and the manufacturer's revenue is maintained or increased.","rationale":"Where the marginal cost of production is low and the untreated population is large, both parties gain from delinking price from volume; subscription also removes the rationing by indication that per-dose pricing forces.","test":"Negotiate a three-year subscription in one or two middle-income countries and compare treated patients, spend and outcomes with matched countries on per-dose pricing.","maturity":"early-clinical","actor":"payer","cost":"large","horizonYears":3},{"id":"idea-sclc-subtype-directed","kind":"idea","name":"Subtype-directed therapy for SCLC (ASCL1 / NEUROD1 / POU2F3 / inflamed)","aka":[],"tldr":"Small-cell lung cancer is at least four diseases under the microscope's uniform appearance. Treat each by its transcription-factor subtype.","summary":"Small-cell lung cancer looks uniform under the microscope, but the Rudin and Gay classification splits it into transcription-factor subtypes: ASCL1-driven SCLC-A, which is DLL3-high and BCL-2 dependent, NEUROD1-driven SCLC-N, POU2F3-driven SCLC-P and the inflamed SCLC-I. The idea is to assign subtype prospectively by RNA or immunohistochemistry and treat each accordingly: tarlatamab for SCLC-A, immunotherapy for SCLC-I, Aurora kinase inhibitors for SCLC-N and PARP or ATR inhibitors for SCLC-P. The rationale is that these dependencies are reproducible in cell lines and xenografts, and a retrospective IMpower133 analysis suggested SCLC-I gained most from atezolizumab. The proposed test is a subtype-stratified umbrella trial in relapsed patients, and the evidence so far is preclinical.","asOf":"2026-09-07","links":[{"label":"DeLLphi-301: tarlatamab, a DLL3-targeting T-cell engager, in previously treated small-cell lung cancer (New England Journal of Medicine 2023)","url":"https://doi.org/10.1056/NEJMoa2307980"},{"label":"ClinicalTrials.gov NCT05740566: DeLLphi-304","url":"https://clinicaltrials.gov/study/NCT05740566"}],"tags":[],"related":["lung-cancer-evidence-roadmap","idea-lung-small-cell-platform-with-shared-controls-and-subtypes"],"cancers":["sclc"],"sections":[],"technologies":[],"targets":["dll3","bcl2","atr","parp"],"drugs":["tarlatamab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-dellphi-301-nejm-2023","paper-dll3-sclc-clin-cancer-res-2019","paper-tarlatamab-sclc-n-engl-j-med-2025"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Prospective subtype assignment (RNA or IHC) will predict benefit: DLL3 engagers in SCLC-A, immunotherapy in SCLC-I, Aurora kinase inhibitors in SCLC-N, and PARP/ATR inhibitors in SCLC-P.","rationale":"Subtype-specific dependencies are reproducible in cell lines and PDX; DLL3 expression tracks ASCL1.","test":"Biomarker-stratified umbrella trial assigning relapsed patients by IHC subtype to tarlatamab, ATR inhibitor, Aurora A inhibitor, or chemo-immunotherapy.","maturity":"preclinical-evidence"},{"id":"idea-pdac-surveillance-for-every-germline-carrier","kind":"idea","name":"Surveillance for every germline carrier found by universal testing, inside a registry rather than a research exception","aka":[],"tldr":"One patient in twenty with pancreatic cancer carries an inherited gene fault, and most have no family history. Guidelines now say test every patient, which finds relatives who carry it too, but the yearly scans that catch cancer at stage I in carriers are still offered only in research programmes. The proposal is to make surveillance follow the test result automatically.","summary":"Hu 2018 found a pathogenic variant in CDKN2A, TP53, MLH1, BRCA2, ATM or BRCA1 in 5.5 percent of 3,030 patients, 5.2 percent of those without a family history; NCCN and ASCO responded with germline testing for all. The CAPS programme showed what surveillance of carriers achieves: 9 of 10 surveillance-detected cancers resectable (Canto 2018), 7 of 9 at stage I in CAPS5, and across 1,731 people a median survival of 9.8 years for screen-detected cancer against 1.5 years outside surveillance (Dbouk 2022). The 2020 CAPS consensus nevertheless asked that surveillance stay in research settings until benefit was shown. The gap is cascade: the patient is tested, the drug decision (platinum, olaparib) is made, and the relatives who test positive have no routine route to annual endoscopic ultrasound or MRI. PRECEDE (20,000 estimated participants, primary completion December 2030) is the scale-up cohort. The proposal is a national registry that enrols every carrier found by cascade testing into protocolised annual imaging with outcomes reported, so that the evidence the consortium asked for is generated by the service rather than in spite of it. UK access and the EUROPAC programme are on the UK and NHS page.","asOf":"2026-09-24","links":[{"label":"CAPS5: stage and survival (JCO 2022)","url":"https://europepmc.org/article/MED/35704792"},{"label":"CAPS Consortium recommendations (Gut 2020)","url":"https://europepmc.org/article/MED/31672839"},{"label":"ClinicalTrials.gov NCT04970056","url":"https://clinicaltrials.gov/study/NCT04970056"}],"tags":["pancreatic-evidence"],"related":["germline-to-parp","early-detection-roadmap"],"cancers":["pancreatic","brca-palb2-pdac"],"sections":[],"technologies":["germline-testing","pancreatic-surveillance","mri"],"targets":["brca"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["gbrca-mutation","germline-vs-somatic"],"trials":["precede"],"people":[],"bottlenecks":["b-hereditary-risk","b-early-detection","b-care-fragmentation"],"keyPapers":["paper-hu-germline-mutations-pancreatic-cancer-risk-jama-2018","paper-canto-caps-long-term-surveillance-gastroenterology-2018","paper-caps-consortium-surveillance-recommendations-gut-2020","paper-dbouk-caps5-stage-survival-jco-2022"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Registry-based annual surveillance of germline carriers identified by cascade testing yields a stage I proportion above 50 percent among detected cancers and a five-year survival above 60 percent, at fewer than 100 scans per cancer or high-grade lesion found.","rationale":"Universal testing already generates the carriers; the surveillance protocol exists; the missing piece is the service pathway and a registry that turns it into evidence.","test":"National registry with protocolised imaging and pre-specified outcomes (stage distribution, resection rate, survival, scans per lesion, overdiagnosis of low-grade cysts) compared with carriers outside surveillance; PRECEDE and CAPS as external comparators.","maturity":"being-tested-at-scale","actor":"policy","cost":"large","horizonYears":6},{"id":"idea-acc-auto-generated-survivorship-plans","kind":"idea","name":"Survivorship care plans generated automatically from the treatment record","aka":[],"tldr":"Every patient finishing treatment should get a clear document listing what they had, what to watch for, and when to be checked. Software can write it from the record so it actually happens.","summary":"Survivorship care plans are recommended by every oncology guideline body but are produced for a minority of patients because writing them by hand takes an hour. Structured treatment data (regimens, cumulative doses, radiation fields, surgery) can be mapped by rules to late-effect risks and evidence-based surveillance schedules (for example, the Children's Oncology Group long-term follow-up guidelines) and rendered for patient and family doctor automatically, with clinician review.","asOf":"2026-09-08","links":[{"label":"Children's Oncology Group long-term follow-up guidelines","url":"http://www.survivorshipguidelines.org/"}],"tags":[],"related":["idea-acc-portable-treatment-summary"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-care-fragmentation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Automated generation will raise survivorship plan delivery from under 30% to above 90% of eligible patients and increase adherence to recommended surveillance (echocardiography after anthracyclines, breast MRI after chest radiotherapy) by at least 25 percentage points.","rationale":"The knowledge is codified in guidelines; the failure is purely one of labour, which software removes.","test":"Implement in three centres and measure plan delivery, surveillance adherence at two years, and primary care physician awareness of late-effect risks.","maturity":"early-clinical","actor":"data","cost":"small","horizonYears":2},{"id":"idea-bio1-first-strike-second-strike","kind":"idea","name":"Switch drugs at maximum response, not at relapse","aka":[],"tldr":"Species go extinct when a second disaster hits a population already shrunk by a first one. Apply the same logic: hit the tumour with a different kind of drug when it is smallest, rather than waiting for it to grow back.","summary":"The first-strike, second-strike model from extinction biology proposes that a therapy switch at nadir, when the residual population is small and less diverse, exploits stochastic extinction and pre-empts the expansion of resistant clones. Current practice continues the first drug until progression, when the population is large and resistant. A trial would randomise patients at best response to a mechanistically distinct second strike versus continuation.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Tumour heterogeneity and clonal evolution): Gerlinger et al., Intratumor heterogeneity and branched evolution (NEJM 2012)","url":"https://doi.org/10.1056/NEJMoa1113205"}],"tags":[],"related":[],"cancers":["nsclc","melanoma"],"sections":[],"technologies":[],"targets":[],"drugs":["lorlatinib"],"companies":[],"institutions":["moffitt"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-tumor-heterogeneity","b-resistance"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"In patients achieving deep response on a targeted agent, a time-limited switch to a non-cross-resistant agent at nadir increases the rate of durable remission at three years compared with continuing the first agent to progression.","rationale":"Small populations are more vulnerable to extinction; the mechanism is well established in ecology and is implicit in consolidation strategies in leukaemia, but has never been tested in solid tumours.","test":"Phase 2 in ALK-positive lung cancer or BRAF melanoma: at confirmed best response, randomise to three months of a different mechanism (for example chemotherapy or an ADC) followed by original therapy, versus continuation; endpoint durable remission at 36 months.","maturity":"speculative","actor":"research","cost":"medium","horizonYears":5},{"id":"idea-prev-hpv-single-dose-switch-catchup","kind":"idea","name":"Switch every country to single-dose HPV vaccination and add catch-up to age 26","aka":[],"tldr":"One dose of HPV vaccine protects as well as two or three. Halving the doses frees supply to vaccinate far more girls, boys and young adults.","summary":"One dose of HPV vaccine protects as well as two or three, so this idea coordinates a switch to single-dose schedules in every country and directs the freed supply to gender-neutral and catch-up vaccination to age 26. KEN SHE and other trials showed single-dose efficacy and WHO recommends one- or two-dose schedules, yet many countries retain two doses; in low-income countries supply and delivery cost rather than hesitancy are the main limits, and a single dose halves both. Progress would be measured by coverage in Gavi-supported countries and HPV16/18 prevalence in 18-year-olds. The test is country-level monitoring as the switch is implemented. Being tested at scale, it addresses the bottlenecks Prevention we already have is not deployed and Most of the world has almost no cancer care.","asOf":"2026-09-08","links":[{"label":"WHO cervical cancer elimination initiative","url":"https://www.who.int/initiatives/cervical-cancer-elimination-initiative"},{"label":"Gavi","url":"https://www.gavi.org"}],"tags":[],"related":[],"cancers":["cervical","head-and-neck"],"sections":["prevention"],"technologies":["hpv-vaccine"],"targets":[],"drugs":[],"companies":[],"institutions":["iarc"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption","b-global-access"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A single-dose switch increases full coverage in Gavi-supported countries by at least 20 percentage points within three years and reduces HPV16/18 prevalence in 18-year-olds by at least half within a decade.","rationale":"Supply and delivery cost, not hesitancy, are the main limits in low-income countries; single dose halves both.","test":"Country-level coverage and prevalence monitoring as the switch is implemented.","maturity":"being-tested-at-scale","actor":"policy","cost":"large","horizonYears":5},{"id":"idea-bio1-epigenetic-silencing-in-vivo","kind":"idea","name":"Switch off an undruggable oncogene permanently with epigenetic editing","aka":[],"tldr":"Instead of blocking a cancer protein, add a chemical off-switch to its gene so the cell stops making it. Early versions of this tool are being tested in other diseases.","summary":"CRISPR-based epigenetic silencers (CRISPRoff and related systems) place heritable DNA methylation and repressive marks at a promoter without cutting DNA. Delivered by lipid nanoparticles, this could durably silence an amplified or overexpressed but undruggable oncogene. Epigenetic editing has entered clinical development for a liver target, establishing delivery and durability precedent in humans.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The undruggable drivers): Dang et al., Drugging the 'undruggable' cancer targets (Nature Reviews Cancer 2017)","url":"https://doi.org/10.1038/nrc.2017.36"}],"tags":[],"related":[],"cancers":["neuroblastoma"],"sections":[],"technologies":["crispr-screens","epigenetic-drugs","methylation-profiling"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-undruggable-targets"],"keyPapers":["paper-dang-nat-rev-cancer"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A single LNP dose of an epigenetic silencer targeting an amplified oncogene achieves durable transcript suppression in tumour tissue for more than four weeks and inhibits tumour growth.","rationale":"Silencing avoids the need for a binding pocket entirely, and heritable repression means dividing tumour cells retain the off state. Tumour-selective delivery remains the main risk.","test":"In a MYCN-amplified neuroblastoma model, compare tumour and liver transcript silencing and durability after systemic LNP dosing, with methylation sequencing to confirm mechanism and off-target promoter analysis.","maturity":"speculative","actor":"research","cost":"medium","horizonYears":9},{"id":"idea-cns-first-adc-strategy","kind":"idea","name":"Systemic-first management of HER2-positive brain metastases","aka":[],"tldr":"With Enhertu and tucatinib controlling brain metastases in most patients, radiation could be reserved for those who do not respond, sparing cognitive side effects.","summary":"This idea would manage asymptomatic or small HER2-positive brain metastases with systemic therapy first, trastuzumab deruxtecan or the tucatinib triplet, holding stereotactic radiosurgery in reserve for lesions that do not respond. Radiation necrosis and cognitive decline are cumulative, whereas DESTINY-Breast12 and HER2CLIMB show systemic agents now achieve intracranial responses comparable to local therapy in many patients. The hypothesis is that systemic-first treatment with deferred radiosurgery is non-inferior on intracranial progression-free survival and superior on neurocognitive outcomes. The test is a randomised trial of upfront versus deferred radiosurgery with neurocognitive function at one year as primary endpoint, addressing the brain-delivery bottleneck.","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT04739761: DESTINY-Breast12","url":"https://clinicaltrials.gov/study/NCT04739761"},{"label":"ClinicalTrials.gov NCT02614794: HER2CLIMB","url":"https://clinicaltrials.gov/study/NCT02614794"}],"tags":[],"related":[],"cancers":["breast-her2-positive"],"sections":[],"technologies":["sbrt"],"targets":[],"drugs":["trastuzumab-deruxtecan","tucatinib"],"companies":[],"institutions":[],"pathways":[],"terms":["her2-brain-metastases"],"trials":["destiny-breast12","her2climb"],"people":[],"bottlenecks":[],"keyPapers":["paper-trastuzumab-deruxtecan-breast-her2-positive-n-engl-j-med-2020","paper-her2climb-brain-lin-jco-2020","paper-tuxedo-1-trastuzumab-deruxtecan-brain-metastases-nat-med-2022"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Systemic-first therapy (T-DXd or tucatinib triplet) with deferred radiosurgery is non-inferior to upfront radiosurgery on intracranial PFS and superior on neurocognitive outcomes.","rationale":"Radiation necrosis and cognitive decline are cumulative; systemic agents now achieve intracranial responses comparable to local therapy in many patients.","test":"Randomised trial of upfront SRS vs deferred SRS with systemic HER2 therapy; primary endpoint neurocognitive function at 12 months, secondary intracranial PFS and OS.","maturity":"early-clinical"},{"id":"idea-acc-tailored-second-cancer-screening","kind":"idea","name":"Tailored screening for second cancers in survivors with known high-risk exposures","aka":[],"tldr":"Survivors who had chest radiotherapy as young women, or certain chemotherapies, have much higher risks of specific second cancers. They should be screened like people with inherited risk, and today most are not.","summary":"Women treated with chest radiotherapy before 30 have breast cancer risks comparable to BRCA carriers and are recommended annual MRI; survivors of Hodgkin lymphoma have elevated lung and gastrointestinal cancer risks; alkylating agents raise leukaemia risk. Uptake of recommended surveillance is low because survivors and their doctors do not know the exposures. Registry-driven identification and invitation to tailored screening, as is done for hereditary syndromes, would apply existing evidence.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Survivorship and late effects are neglected): NCI Office of Cancer Survivorship statistics","url":"https://cancercontrol.cancer.gov/ocs/statistics"}],"tags":[],"related":[],"cancers":["hodgkin-lymphoma","breast-hr-positive"],"sections":[],"technologies":["mri"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-early-detection"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Registry-driven invitation will raise adherence to recommended second-cancer surveillance among high-risk survivors from under 40% to above 75%, and will shift second cancers to earlier stage at diagnosis.","rationale":"Organised invitation is what makes population screening work; high-risk survivors are a defined, findable population with strong evidence for surveillance.","test":"A randomised trial of registry-driven invitation versus usual care among 5,000 high-risk survivors with adherence and stage at second-cancer diagnosis as endpoints.","maturity":"early-clinical","actor":"clinic","cost":"medium","horizonYears":4},{"id":"idea-crc-ctdna-de-escalation-beyond-stage-ii","kind":"idea","name":"Take ctDNA-guided de-escalation beyond stage II, and stop escalating on a positive result until a trial says it helps","aka":[],"tldr":"A blood test after surgery already lets stage II colon cancer patients skip chemotherapy safely. The same test in stage III would spare far more people, and the unproven half, giving more chemotherapy to those who test positive, has so far changed nothing.","summary":"DYNAMIC randomised 455 patients with stage II colon cancer and cut adjuvant chemotherapy use from 28 to 15 percent with two-year recurrence-free survival of 93.5 against 92.4 percent, non-inferior against a margin of 8.5 percentage points. GALAXY, in 1,039 patients across stages II to IV, found a hazard ratio of 10.0 for recurrence with a positive test four weeks after surgery and showed adjuvant chemotherapy benefit concentrated in the positives (hazard ratio 6.59).\n\nBoth halves of the strategy are unfinished. De-escalation is proven only in stage II, where QUASAR put the absolute survival benefit of chemotherapy at 3.6 percent to begin with; the far larger prize is the stage III population where six months of oxaliplatin is routine and 60 to 70 percent of patients are cured by surgery alone. Escalation has no positive trial at all: the ALTAIR arm of CIRCULATE-Japan, which added trifluridine-tipiracil for ctDNA-positive patients, did not improve outcomes, and this idea takes that as evidence that a more intensive version of the same drug class is the wrong response to a positive test.","asOf":"2026-09-24","links":[{"label":"Tie et al.: DYNAMIC (N Engl J Med 2022)","url":"https://europepmc.org/article/MED/35657320"},{"label":"Kotani et al.: GALAXY (Nat Med 2023)","url":"https://europepmc.org/article/MED/36646802"},{"label":"ClinicalTrials.gov NCT05174169","url":"https://clinicaltrials.gov/study/NCT05174169"},{"label":"ClinicalTrials.gov NCT04120701","url":"https://clinicaltrials.gov/study/NCT04120701"}],"tags":["colorectal-evidence"],"related":["colorectal-roadmap","ctdna-tests","idea-ctdna-guided-adjuvant-crc"],"cancers":["colorectal","colon-cancer"],"sections":["diagnostics","chemotherapy"],"technologies":["mrd-testing","liquid-biopsy","signatera","ngs"],"targets":[],"drugs":["folfox","capox","capecitabine"],"companies":["natera","guardant-health"],"institutions":[],"pathways":[],"terms":["ctdna","mrd","neoadjuvant-adjuvant"],"trials":["dynamic","circulate-japan"],"people":[],"bottlenecks":["b-dormancy-mrd","b-toxicity-qol","b-biomarker-validation"],"keyPapers":["paper-dynamic-nejm-2022","paper-galaxy-signatera-nat-med-2023","paper-tie-ctdna-minimal-residual-disease-stage-ii-colon-sci-transl-med-2016","paper-idea-duration-adjuvant-stage-iii-colon-nejm-2018"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"In stage III colon cancer, a ctDNA-negative result at four to seven weeks after surgery identifies a group in whom three months of a fluoropyrimidine alone is non-inferior to six months of oxaliplatin-based chemotherapy for three-year disease-free survival, while a positive result identifies a group whose outcome is unchanged by intensifying the same cytotoxic backbone and who should instead be randomised to a mechanistically different agent.","rationale":"The prognostic separation is an order of magnitude, larger than any clinicopathological factor; the de-escalation half has already survived a randomised test in stage II; and the failure of cytotoxic escalation in ALTAIR argues that the positive group needs a different class of drug rather than more of the same.","test":"CIRCULATE-US (NRG-GI008), the French CIRCULATE and DYNAMIC-III readouts, with a pre-registered pooled individual patient analysis across stage III; for the positive group, a separate randomisation to a biology-matched agent rather than to intensified chemotherapy, with three-year disease-free survival as the primary endpoint and chemotherapy exposure and persistent neuropathy as co-primary harms.","maturity":"being-tested-at-scale","actor":"clinic","cost":"large","horizonYears":5},{"id":"idea-bio2-fmt-plus-checkpoint-phase3","kind":"idea","name":"Take faecal transplant plus immunotherapy to a definitive trial","aka":[],"tldr":"Transferring gut bacteria from patients who responded to immunotherapy has helped some patients who had stopped responding. It is time for a proper large trial.","summary":"Two independent phase 1 studies reported that faecal microbiota transplant from checkpoint responders re-sensitised some anti-PD-1-refractory melanoma patients, and a first-line study of donor transplant with checkpoint blockade showed feasibility and encouraging response. The field has stayed in small single-arm studies for years. A randomised trial with a defined donor consortium, standardised product and pre-specified microbiome endpoints would settle whether the effect is real.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (No one can predict who responds to immunotherapy): Haslam & Prasad (JAMA Network Open 2019)","url":"https://doi.org/10.1001/jamanetworkopen.2019.2535"}],"tags":[],"related":[],"cancers":["melanoma","rcc"],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":[],"drugs":["pembrolizumab","nivolumab"],"companies":[],"institutions":["gustave-roussy","princess-margaret"],"pathways":[],"terms":[],"trials":[],"people":["laurence-zitvogel"],"bottlenecks":["b-immunotherapy-response","b-tme-immunosuppression"],"keyPapers":["paper-haslam-jama-netw-open"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Faecal microbiota transplant from selected responder donors plus anti-PD-1 improves response rate compared with anti-PD-1 alone in checkpoint-refractory melanoma, with engraftment of donor taxa as a mechanistic mediator.","rationale":"The mouse causal data are strong, human phase 1 signals are reproducible across two centres, and the intervention is inexpensive. The main risks are donor variability and product standardisation, both addressable through consortium banking.","test":"A randomised phase 2 with pooled standardised donor product, primary endpoint objective response, and mandatory metagenomic sequencing to link engraftment with response.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":5},{"id":"idea-prostate-bipolar-androgen-therapy-phase-3-on-pfs2","kind":"idea","name":"Take high-dose testosterone to phase 3, with progression-free survival through the second line as the primary endpoint","aka":["bipolar androgen therapy phase 3","supraphysiological testosterone prostate phase 3","BAT resensitisation trial"],"tldr":"Giving men with castration-resistant prostate cancer large doses of the hormone the treatment has spent years removing makes a third of them respond, and makes half of them respond again to the drug that had stopped working. It has never been taken to a definitive trial, partly because the endpoint that shows the benefit is not the one trials usually use.","summary":"RESTORE gave monthly testosterone cipionate 400 mg to 30 men who had progressed on enzalutamide: 9 of 30 (30 percent) had a 50 percent prostate-specific antigen fall, and 15 of 21 (52 percent) responded when re-challenged with enzalutamide afterwards. TRANSFORMER randomised the approach against enzalutamide in 195 men and found progression-free survival of 5.7 months in both arms, but progression-free survival through crossover of 28.2 against 19.6 months in favour of testosterone first (hazard ratio 0.44, P equals 0.02), prostate-specific antigen progression-free survival on enzalutamide of 10.9 months after testosterone against 3.8 months after abiraterone, and quality of life consistently favouring testosterone.\n\nThe drug is an old generic. There is no commercial sponsor with a reason to run the trial, and the primary endpoint that regulators are used to, progression-free survival on the assigned treatment, is precisely the one on which the approach is flat, because the benefit is resensitisation rather than direct cytotoxicity. That combination is why a treatment with a randomised signal and a quality-of-life advantage has sat at phase 2 since 2021. The proposal is a publicly funded phase 3 in asymptomatic men with low-volume castration-resistant disease, powered on progression-free survival through the second line, with overall survival and patient-reported outcomes as key secondaries.\n\nWhat any of this means for someone treated in Britain, from the screening committee's position and the NICE appraisals to scanner and radiotherapy capacity, waiting times and how to reach a trial, is on the UK and NHS pathway page for prostate cancer.","asOf":"2026-09-25","links":[],"tags":["prostate-evidence"],"related":["idea-bio1-alternating-schedules","idea-tr1-adaptive-therapy-randomised-phase-2","idea-moon-generics-for-cancer-fund","prostate-roadmap"],"cancers":["prostate","prostate-mcrpc"],"sections":["hormonal"],"technologies":[],"targets":["androgen-receptor"],"drugs":["enzalutamide","abiraterone"],"companies":[],"institutions":["johns-hopkins"],"pathways":[],"terms":["castration-resistance","psa","quality-of-life","bipolar-androgen-therapy","intermittent-androgen-deprivation"],"trials":[],"people":[],"bottlenecks":["b-generic-repurposing","b-incentive-misalignment","b-resistance","b-trial-design","b-toxicity-qol"],"keyPapers":["paper-teply-restore-bipolar-androgen-therapy-lancet-oncol-2018","paper-denmeade-transformer-bipolar-androgen-therapy-jco-2021","paper-chen-androgen-receptor-overexpression-antiandrogen-resistance-nat-med-2004","paper-visakorpi-androgen-receptor-amplification-nat-genet-1995","paper-antonarakis-ar-v7-resistance-nejm-2014"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"In asymptomatic men with metastatic castration-resistant prostate cancer and no high-risk sites for tumour flare, a strategy of bipolar androgen therapy followed at progression by an androgen receptor pathway inhibitor improves progression-free survival through the second line and patient-reported quality of life against the reverse strategy, without a detriment in overall survival.","rationale":"The mechanism follows directly from the biology of resistance in this disease: castration-resistant cells adapt by amplifying and overexpressing the androgen receptor, which Visakorpi and Chen established, and a cell adapted to a low-ligand environment is vulnerable to a high-ligand one. The clinical signal is randomised, not anecdotal, and it is a sequence effect of 8.6 months in PFS2 with a hazard ratio of 0.44. The quality-of-life direction is unusual: almost every intensification in this disease costs the patient something, and this one does not. The barrier is commercial rather than scientific, which makes it exactly the kind of question a public funder should pick up, and the endpoint problem is soluble by naming PFS2 in the protocol rather than discovering it in the secondary analysis.","test":"A publicly funded randomised phase 3 in asymptomatic men with metastatic castration-resistant prostate cancer, excluding those with more than five visceral sites or bone lesions at risk of fracture, randomised to bipolar androgen therapy followed by an androgen receptor pathway inhibitor at progression, or to an androgen receptor pathway inhibitor followed by bipolar androgen therapy. Primary endpoint progression-free survival through the second line; key secondary endpoints overall survival, patient-reported quality of life and sexual function, and cardiovascular and thromboembolic events. Stratify on prior androgen receptor pathway inhibitor exposure and on AR-V7 status. Roughly 500 men and five years.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":6},{"id":"idea-prev-mobile-lung-screening-deprived-areas","kind":"idea","name":"Take lung screening scanners to supermarket car parks in the poorest areas","aka":[],"tldr":"People most at risk of lung cancer are least likely to attend hospital screening. Manchester showed mobile scanners in car parks reach them. Make this the default model.","summary":"The Manchester Lung Health Check found high uptake and a stage shift (about 80% stage I-II) using mobile CT in deprived communities. Propose that national lung screening programmes mandate mobile delivery with same-day cessation support in the most deprived quintile, with uptake and stage as performance metrics.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The hardest cancers are found late): Crosby et al., Early detection of cancer (Science 2022)","url":"https://doi.org/10.1126/science.aay9040"}],"tags":[],"related":["lung-cancer-evidence-roadmap","idea-lung-deprivation-gradient-treated-as-a-defect-in-delivery"],"cancers":["nsclc"],"sections":["early-detection"],"technologies":["ct"],"targets":[],"drugs":[],"companies":[],"institutions":["the-christie"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-early-detection","b-prevention-adoption"],"keyPapers":["paper-crosby-science"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Mobile delivery in deprived areas raises uptake from about 30% to at least 50% and yields early-stage detection rates matching affluent fixed-site screening.","rationale":"Travel, cost, and mistrust of hospitals are the barriers; the fix is logistics.","test":"Compare uptake and stage in mobile versus fixed-site delivery within the same programme.","maturity":"being-tested-at-scale","actor":"policy","cost":"medium","horizonYears":3},{"id":"idea-bio2-circadian-mrd-sampling","kind":"idea","name":"Take the blood test, and give the drug, at the right time of day","aka":[],"tldr":"Cancer cells enter the blood mostly during rest, so a morning blood test may miss them. Sampling and dosing at the right hour may be a free improvement.","summary":"Circulating tumour cell shedding in breast cancer patients and mouse models peaks during the rest phase, with several-fold differences between night and day samples. Almost all clinical sampling occurs in clinic hours, and almost all therapy is delivered in clinic hours. If shedding and proliferation are circadian, both assay sensitivity and drug timing are currently set by convenience.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Dormant cells and minimal residual disease): Tie et al., ctDNA analysis guiding adjuvant therapy in stage II colon cancer (NEJM 2022)","url":"https://doi.org/10.1056/NEJMoa2200075"}],"tags":[],"related":[],"cancers":["breast-hr-positive"],"sections":[],"technologies":["liquid-biopsy","mrd-testing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["ctdna","mrd"],"trials":[],"people":["klaus-pantel"],"bottlenecks":["b-dormancy-mrd","b-biomarker-validation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Plasma ctDNA and CTC yield are at least twofold higher in samples taken during the rest phase, raising MRD assay sensitivity without any change in chemistry; and rest-phase dosing of a cycle-dependent agent increases kill of shed cells.","rationale":"Chronotherapy has reproducible pharmacokinetic effects and a randomised precedent in colorectal chemotherapy timing. Sampling time is the cheapest variable in the whole MRD pipeline and has never been optimised.","test":"A crossover sampling study of 60 patients with paired rest-phase and active-phase draws analysed by the same assay; if yield differs, change guidance and then test timed dosing.","maturity":"preclinical-evidence","actor":"research","cost":"small","horizonYears":4},{"id":"idea-prame-tcr-beyond-a02","kind":"idea","name":"TCR therapeutics for non-HLA-A*02 patients","aka":[],"tldr":"Today's T-cell-receptor drugs only work for people with one tissue type. Building versions for the other common types would roughly double who can be treated.","summary":"The idea is to build PRAME-directed ImmTAC T-cell engagers for patients who carry HLA-A*24:02 or HLA-A*11:01 rather than HLA-A*02:01, the tissue type that tebentafusp and brenetafusp currently require. The antigen and format stay the same and only the HLA context changes, in principle a solved engineering problem; Immunocore and others already have preclinical ImmTACs against PRAME on HLA-A*24 and A*11, common in East Asian populations. The hypothesis is that these agents match the activity and safety of the A*02 drug, roughly doubling the number of people who could be treated. The test is a phase 1 dose escalation in HLA-A*24:02-positive melanoma in Japan and Korea mirroring IMCgp100-202; the evidence is preclinical and the idea bears on HLA-A*02:01 restriction.","asOf":"2026-09-07","links":[],"tags":[],"related":[],"cancers":["melanoma"],"sections":[],"technologies":["t-cell-engager","tcr-t"],"targets":["prame"],"drugs":["brenetafusp","tebentafusp"],"companies":[],"institutions":[],"pathways":[],"terms":["hla-a02-restriction"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-imcgp100-202-n-engl-j-med-2021","paper-imcgp100-202-n-engl-j-med-2023-update","paper-tebentafusp-melanoma-cancers-basel-2019"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"PRAME-directed ImmTACs restricted to HLA-A*24:02 or A*11:01 achieve comparable activity and safety to the A*02 agent.","rationale":"Same antigen, same format; the only variable is the HLA context, which is a solved engineering problem in principle.","test":"Phase 1 dose escalation in HLA-A*24:02-positive melanoma in Japan and Korea, with ctDNA and OS follow-up mirroring IMCgp100-202.","maturity":"preclinical-evidence"},{"id":"idea-fund-ten-year-hard-problem-awards","kind":"idea","name":"Ten-year awards for scientists who commit to one hard problem","aka":[],"tldr":"Give a small number of scientists a decade of guaranteed funding to work on a single hard problem such as dormant cancer cells, with no pressure to publish quickly.","summary":"The typical grant cycle of three to five years pushes researchers towards problems that yield papers on that timescale. Metastasis, dormancy, cachexia, tumour immunology in cold tumours and undruggable drivers need longer bets. A funder would award 10-year, person-based grants to mid-career investigators who commit to one such problem, assessed at year five on process (data shared, tools built, negative results published) rather than publication counts. Precedents are the Howard Hughes Medical Institute investigator model and the Wellcome Trust's long-term fellowships.","asOf":"2026-09-08","links":[{"label":"HHMI Investigator Program","url":"https://www.hhmi.org/programs/biomedical-research/investigator-program"}],"tags":[],"related":["idea-fund-metastasis-moonshot","idea-fund-cachexia-programme"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["klaus-pantel","charles-swanton"],"bottlenecks":["b-funding-allocation","b-metastasis-biology","b-dormancy-mrd"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Ten-year awardees working on metastasis, dormancy or cachexia produce more high-impact, reproducible findings per dollar by year ten than matched investigators on conventional grants, with more tool and model outputs and fewer but larger papers.","rationale":"Studies of HHMI investigators show they produce more highly-cited and more novel work, and more flops, than matched NIH R01 holders; the freedom to fail is what makes long problems approachable. Cancer philanthropy already runs people-based programmes but mostly with short horizons.","test":"Fund 20 awardees against 20 matched controls and pre-register the comparison metrics (novelty of citations, replication rate of key claims, tools adopted by others) for assessment at years five and ten.","maturity":"speculative","actor":"philanthropy","cost":"medium","horizonYears":7},{"id":"idea-bio2-fibre-diet-io-trial","kind":"idea","name":"Test a high-fibre diet as an immunotherapy adjunct","aka":[],"tldr":"People who eat more fibre appear to respond better to immunotherapy, while some probiotic supplements may do the opposite. A proper trial would settle it.","summary":"Observational data in melanoma associate higher dietary fibre intake with improved checkpoint response, and over-the-counter probiotic use with worse response, with supporting mouse experiments. Diet is a cheap, scalable and modifiable exposure but has never been tested randomly alongside checkpoint therapy with microbiome and immune endpoints. Adherence measurement, through stool short-chain fatty acids, makes a rigorous trial possible.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (No one can predict who responds to immunotherapy): Haslam & Prasad (JAMA Network Open 2019)","url":"https://doi.org/10.1001/jamanetworkopen.2019.2535"}],"tags":[],"related":[],"cancers":["melanoma","nsclc"],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":[],"drugs":[],"companies":[],"institutions":["md-anderson"],"pathways":[],"terms":[],"trials":[],"people":["laurence-zitvogel"],"bottlenecks":["b-immunotherapy-response","b-tme-immunosuppression","b-generic-repurposing"],"keyPapers":["paper-haslam-jama-netw-open"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A supervised high-fibre dietary intervention during checkpoint therapy improves response rate compared with usual diet, with stool short-chain fatty acid levels mediating the effect.","rationale":"Fibre fermentation produces short-chain fatty acids that alter T-cell differentiation, giving a plausible mechanism, and the observational effect size reported in melanoma was large. The intervention has no toxicity and independent health benefits.","test":"A randomised trial of provided high-fibre meals versus usual diet in patients starting checkpoint blockade, with objective response as primary endpoint and stool metabolomics and metagenomics as mechanistic endpoints.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":5},{"id":"idea-tr2-alternating-vs-concurrent","kind":"idea","name":"Test alternating drug schedules against giving both drugs at once","aka":[],"tldr":"Two drugs might work better given in turns rather than together, with less toxicity. Almost no trial has tested this.","summary":"Evolutionary models and mouse studies suggest that alternating two non-cross-resistant agents can delay resistance as well as concurrent dosing at lower cumulative toxicity, and that some pairs are antagonistic when concurrent (for example cytostatic agents that protect cells from cytotoxics). Randomised trials of schedule rather than of drug are rare.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Too many combinations to test): Palmer & Sorger, Combination cancer therapy can confer benefit via patient-to-patient variability without drug additivity or synergy (Cell 2017)","url":"https://doi.org/10.1016/j.cell.2017.11.009"}],"tags":[],"related":[],"cancers":["nsclc"],"sections":[],"technologies":[],"targets":[],"drugs":["osimertinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["flaura2"],"people":[],"bottlenecks":["b-combination-space","b-resistance"],"keyPapers":["paper-flaura-nejm-2018","paper-flaura2-long-term-safety-lung-cancer-2026","paper-mariposa-nejm-2024","paper-palmer-cell"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"For at least one common doublet (for example an EGFR TKI plus chemotherapy in EGFR-mutant lung cancer), an alternating schedule achieves non-inferior progression-free survival with at least 30% fewer grade 3 or worse adverse events than concurrent dosing.","rationale":"FLAURA2 showed concurrent osimertinib plus chemotherapy improves progression-free survival but with substantial added toxicity. Cell-cycle arguments predict that sequence within a cycle matters.","test":"A randomised phase 2 of concurrent versus alternating osimertinib and platinum-pemetrexed with progression-free survival and toxicity endpoints, plus ctDNA kinetics to compare resistance emergence.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":4},{"id":"idea-bio1-aged-comorbid-models","kind":"idea","name":"Test cancer drugs in old and unhealthy animals, not just young fit ones","aka":[],"tldr":"Most cancer patients are older and have other illnesses, but nearly all animal experiments use young healthy mice. Results may not transfer.","summary":"Ageing changes immune function, drug metabolism, marrow reserve and the tumour microenvironment; obesity and diabetes alter drug distribution and immunotherapy response. Efficacy and toxicity studies in aged, obese or comorbid animals cost more and take longer, so they are rarely done. Requiring at least one aged-cohort confirmation before first-in-human studies of immunotherapies would be a targeted change.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Lab models that fail to predict what happens in patients): Wong, Siah & Lo, Estimation of clinical trial success rates (Biostatistics 2019)","url":"https://doi.org/10.1093/biostatistics/kxx069"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["irae"],"trials":[],"people":[],"bottlenecks":["b-preclinical-models","b-aging-comorbidity"],"keyPapers":["paper-wong-biostatistics"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"For a meaningful minority of agents, efficacy or toxicity in aged or obese animals differs materially from young lean animals in a direction that predicts clinical experience in older patients.","rationale":"Age-related immune decline is documented in mice and humans, and obesity paradoxically improves some immunotherapy outcomes; these interactions are invisible in the standard young mouse.","test":"Repeat pivotal efficacy studies for ten agents with known clinical outcomes in aged and diet-induced obese cohorts and compare which model better matches the clinical result.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":4},{"id":"idea-tr1-pre-emptive-pharmacogenomic-testing","kind":"idea","name":"Test DPYD, UGT1A1 and TPMT/NUDT15 before the first dose, everywhere","aka":[],"tldr":"A cheap gene test for DPYD, UGT1A1 and TPMT or NUDT15 before fluoropyrimidines, irinotecan or thiopurines identifies people at risk of severe or fatal toxicity so their dose can be lowered. The EMA has recommended DPD testing since 2020; US uptake remains partial.","summary":"Mandatory pre-treatment genotyping for DPYD variants before fluoropyrimidines, UGT1A1*28 and *6 before irinotecan, and TPMT/NUDT15 before thiopurines, with genotype-guided dose reduction per CPIC guidelines, reimbursed and built into chemotherapy order sets. The EMA recommended DPD testing in 2020 and a prospective Dutch study showed genotype-guided dosing reduced severe toxicity; US uptake remains partial.","asOf":"2026-09-08","links":[{"label":"CPIC guideline: fluoropyrimidines and DPYD","url":"https://cpicpgx.org/guidelines/guideline-for-fluoropyrimidines-and-dpyd/"},{"label":"EMA: fluorouracil and related substances (DPD testing)","url":"https://www.ema.europa.eu/en/medicines/human/referrals/fluorouracil-fluorouracil-related-substances-capecitabine-tegafur-flucytosine-containing-medicinal-products"}],"tags":[],"related":[],"cancers":["colorectal","gastric","pancreatic"],"sections":[],"technologies":["cytotoxic-chemotherapy","germline-testing","topoisomerase-inhibitors"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-dose-optimisation","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Universal pre-emptive genotyping with guided dosing will reduce severe fluoropyrimidine toxicity by more than half among variant carriers and reduce toxicity-related hospitalisations at population level without reducing efficacy.","rationale":"The evidence for DPYD is prospective and the test is inexpensive; the barrier is implementation and reimbursement, not science.","test":"Implementation trial across a health system: order-set-integrated genotyping versus usual care, with severe toxicity and hospitalisation as outcomes and cost-effectiveness analysis.","maturity":"being-tested-at-scale","actor":"payer","cost":"small","horizonYears":2},{"id":"idea-bio1-tumour-slice-cultures","kind":"idea","name":"Test drugs on freshly cut slices of the patient's own tumour","aka":[],"tldr":"A thin slice of a tumour, kept alive for a few days, still contains the immune cells and scaffolding that lab-grown cells lose. Drugs can be tested on it directly.","summary":"Precision-cut tumour slices preserve native architecture, stroma, vasculature remnants and resident immune cells for several days, and have been used to measure responses to chemotherapy, targeted agents and immunotherapy with imaging and single-cell readouts. They avoid the selection and adaptation that occur during organoid derivation, at the cost of a short experimental window.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Lab models that fail to predict what happens in patients): Wong, Siah & Lo, Estimation of clinical trial success rates (Biostatistics 2019)","url":"https://doi.org/10.1093/biostatistics/kxx069"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["functional-drug-testing","organoids","single-cell-spatial"],"targets":[],"drugs":[],"companies":["curesponse"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-preclinical-models"],"keyPapers":["paper-wong-biostatistics"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Slice-culture drug response measured within 72 hours predicts clinical response with accuracy at least equal to organoids, and does so for the majority of patients rather than only those whose organoids grow.","rationale":"Organoid derivation succeeds in a variable fraction of samples and takes weeks, which excludes patients who need decisions now; slices work on almost every resection or core.","test":"Paired study on 100 resections: derive both slices and organoids, treat both with the patient's regimen, and compare success rate, turnaround time and clinical concordance.","maturity":"preclinical-evidence","actor":"research","cost":"small","horizonYears":3},{"id":"idea-bio2-functional-precision-rare","kind":"idea","name":"Test drugs on the patient's own cancer cells when there is no trial to join","aka":[],"tldr":"For rare cancers there is often no genetic clue and no trial to join. Testing drugs directly on the patient's fresh tumour cells has guided treatment with reported benefit in a randomised haematology study and in paediatric case series; turnaround and tissue quality are the barriers.","summary":"Functional precision medicine, ex vivo drug sensitivity testing on fresh patient material, guided treatment with reported benefit in a randomised haematology study and in paediatric and rare solid tumour case series. Turnaround, tissue quality and the absence of standardised reporting are the barriers. For rare cancers where genomics is uninformative, function is the only remaining evidence source.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Rare and paediatric cancers without markets): Gatta et al., Rare cancers are not so rare: the rare cancer burden in Europe (EJC 2011)","url":"https://doi.org/10.1016/j.ejca.2011.08.008"}],"tags":[],"related":[],"cancers":["sarcoma","cholangiocarcinoma"],"sections":[],"technologies":["functional-drug-testing","organoids","bh3-profiling","pdx-models"],"targets":[],"drugs":[],"companies":["curesponse","xilis","champions-oncology","sengine"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-rare-cancers","b-preclinical-models","b-biomarker-validation"],"keyPapers":["paper-gatta-eur-j-cancer"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Ex vivo sensitivity-guided therapy improves progression-free survival ratio compared with the patient's own prior line in rare cancers without actionable mutations, in at least a third of tested patients.","rationale":"Functional testing bypasses the need for a biomarker hypothesis, which is what makes it suited to rare and unclassifiable tumours. Haematology results show the approach can outperform physician choice when turnaround is fast enough.","test":"A multi-centre study in rare solid tumours reporting assay success rate, turnaround, proportion of patients whose treatment changes, and progression-free survival ratio against their own prior line.","maturity":"early-clinical","actor":"clinic","cost":"medium","horizonYears":5},{"id":"idea-prostate-hrr-testing-at-metastatic-diagnosis","kind":"idea","name":"Test every man for DNA repair faults on the day his prostate cancer is found to have spread, not three treatments later","aka":["HRR testing at metastatic diagnosis","germline and tumour DNA repair testing timing prostate"],"tldr":"About one man in eight with prostate cancer that has spread carries an inherited DNA repair fault, and about one in five has one in the tumour. The drugs for those faults have moved to the beginning of treatment, but the test is still usually done near the end, when it is too late to use the result.","summary":"The evidence for testing is settled. Pritchard found presumed deleterious germline DNA repair mutations in 11.8 percent of 692 men with metastatic prostate cancer, against 4.6 percent in localised disease and 2.7 percent in a population without a cancer diagnosis, and found no relation to family history or age at diagnosis. Robinson found BRCA2, BRCA1 and ATM aberrations in 19.3 percent of 150 prospectively sequenced metastatic biopsies, and Chung found homologous recombination repair alterations in 23 percent of 3,476 routinely profiled tumours. Both germline and somatic BRCA alterations predict response to a PARP inhibitor, as TRITON2 showed.\n\nWhat has changed is when the answer is needed. PARP inhibitors were licensed after an androgen receptor drug and a taxane; PROpel, TALAPRO-2 and MAGNITUDE moved them to first-line castration-resistant disease, and TALAPRO-3 and AMPLITUDE have moved them into hormone-sensitive disease. A result that arrives after two lines of treatment can no longer be acted on in the setting where the drug is licensed. The proposal is to make combined germline and tumour homologous recombination repair testing an automatic step triggered by the diagnosis of metastasis, in the same way a hormone receptor stain is triggered by a breast biopsy, with the result reported before the first systemic treatment is chosen and with the germline half routed to a family testing pathway.\n\nWhat any of this means for someone treated in Britain, from the screening committee's position and the NICE appraisals to scanner and radiotherapy capacity, waiting times and how to reach a trial, is on the UK and NHS pathway page for prostate cancer.","asOf":"2026-09-25","links":[],"tags":["prostate-evidence"],"related":["idea-prev-reflex-germline-testing","prostate-roadmap","targeted-therapy-roadmap"],"cancers":["prostate","prostate-mhspc","prostate-mcrpc","prostate-nmcrpc"],"sections":["diagnostics","targeted-therapy","prevention"],"technologies":["germline-testing","ngs","liquid-biopsy"],"targets":["brca","atm","cdk12"],"drugs":["olaparib","rucaparib","niraparib","talazoparib"],"companies":["astrazeneca","johnson-johnson","pfizer","myriad-genetics","foundation-medicine"],"institutions":[],"pathways":[],"terms":["genome-wide-loss-of-heterozygosity"],"trials":[],"people":[],"bottlenecks":["b-hereditary-risk","b-biomarker-validation","b-care-fragmentation","b-knowledge-diffusion"],"keyPapers":["paper-pritchard-inherited-dna-repair-metastatic-prostate-nejm-2016","paper-robinson-integrative-clinical-genomics-advanced-prostate-cell-2015","paper-chung-comprehensive-genomic-profiling-prostate-jco-po-2019","paper-abida-triton2-rucaparib-brca-jco-2020","paper-fizazi-triton3-rucaparib-nejm-2023","paper-nct04821622-n-engl-j-med-2026"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Reflex germline and tumour homologous recombination repair testing at the moment of metastatic diagnosis, rather than on clinician request at castration resistance, increases the proportion of eligible men who receive a PARP inhibitor in the setting where it is licensed, increases the proportion of first-degree relatives who are offered cascade testing, and does so at a testing cost per actionable result lower than the cost of the current late pathway, which sequences men who never reach the relevant line.","rationale":"Three things make the timing argument rather than the testing argument the live one. First, carriers cannot be identified clinically: Pritchard showed mutation frequency does not differ by family history or age, so selective testing misses most of them. Second, the drug has moved: the licensed settings for PARP inhibition now start at first-line castration-resistant and, in TALAPRO-3 and AMPLITUDE, hormone-sensitive disease, which is before most men are currently tested. Third, the test result has a second use that is lost entirely by testing late, which is the 8 percent of men in the Stand Up To Cancer cohort with an actionable pathogenic germline alteration whose relatives carry breast, ovarian and pancreatic risk. Testing at metastatic diagnosis also takes place when tumour tissue is more likely to be available and adequate; TRITON3 screened 4,855 men to randomise 405, which is the cost of finding carriers late and one at a time.","test":"A stepped-wedge implementation trial across cancer networks, switching from clinician-requested testing to a reflex order fired by the coding of metastatic prostate cancer. Co-primary outcomes: the proportion of men with a homologous recombination repair result available before first-line systemic treatment is chosen, and the proportion of identified germline carriers whose first-degree relatives are offered testing within 12 months. Secondary outcomes: PARP inhibitor use in the licensed setting, turnaround time, tissue adequacy failure rate, and cost per actionable result against the current pathway. Two to three years, and it can be run inside an existing service rather than as a new trial infrastructure.","maturity":"early-clinical","actor":"clinic","cost":"medium","horizonYears":3},{"id":"idea-prev-vus-saturation-editing-consortium","kind":"idea","name":"Test every possible mutation in every cancer gene so no result is 'uncertain'","aka":[],"tldr":"Genetic testing often returns a variant of uncertain significance that cannot be acted on, most often in people of non-European ancestry. Saturation genome editing has already classified nearly all BRCA1 single-nucleotide variants; a consortium doing the same for the roughly 30 actionable hereditary cancer genes would end most uncertain results.","summary":"Patients often receive a genetic result of uncertain significance that cannot be acted on, so this idea forms a philanthropy-funded consortium to produce saturation genome editing functional maps for the roughly 30 actionable hereditary cancer genes and submit them to ClinVar. Saturation editing has already classified nearly all BRCA1 single-nucleotide variants, VUS rates are especially high in non-European populations, and functional evidence is now accepted in ACMG classification frameworks. The test funds five genes a year and tracks VUS reclassification rates in clinical laboratories. With preclinical evidence, it addresses the bottlenecks Inherited risk is mostly unidentified and Biomarkers are not validated or standardised, and links to CRISPR functional genomics, BRCA and TP53.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Inherited risk is mostly unidentified): Childers et al., National estimates of genetic testing in women with breast or ovarian cancer (JCO 2017)","url":"https://doi.org/10.1200/JCO.2017.73.6314"}],"tags":[],"related":["clinvar"],"cancers":[],"sections":["prevention"],"technologies":["crispr-screens"],"targets":["brca","tp53"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["vus"],"trials":[],"people":[],"bottlenecks":["b-hereditary-risk","b-biomarker-validation"],"keyPapers":["paper-childers-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Complete functional maps resolve at least 80% of current variants of uncertain significance in hereditary cancer genes within five years.","rationale":"VUS rates of 20-40% in non-European populations undermine testing, and functional evidence is now accepted by ACMG classification frameworks.","test":"Fund five genes per year and track VUS reclassification rates in clinical laboratories.","maturity":"preclinical-evidence","actor":"philanthropy","cost":"medium","horizonYears":4},{"id":"idea-tr1-weight-based-vs-flat-dosing-trials","kind":"idea","name":"Test flat versus weight-based dosing of antibodies, and use dose banding to cut waste","aka":[],"tldr":"Monoclonal antibodies and ADCs have moved from weight-based to flat dosing on modelling alone, which is convenient but gives lighter patients relatively more drug. Randomised or pharmacokinetic comparisons, plus rounding doses to vial sizes where exposure is equivalent, could keep effectiveness while cutting cost and waste.","summary":"Randomised or PK-bridging comparisons of flat versus weight-based (or weight-banded) dosing for monoclonal antibodies and ADCs where flat dosing was adopted on modelling alone; pharmacy dose-banding and vial sharing implemented as policy where exposure equivalence is shown. Payers fund the trials; savings are large because these agents dominate oncology drug spend.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Wrong doses): FDA Oncology Center of Excellence, Project Optimus","url":"https://www.fda.gov/about-fda/oncology-center-excellence/project-optimus"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["monoclonal-antibody","adc"],"targets":[],"drugs":["pembrolizumab","trastuzumab-deruxtecan"],"companies":[],"institutions":[],"pathways":[],"terms":["ild"],"trials":[],"people":[],"bottlenecks":["b-dose-optimisation","b-drug-pricing"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Weight-based or banded dosing will be non-inferior to flat dosing for efficacy in most agents studied while reducing drug consumption by 10-25 percent in lighter patients and reducing toxicity for ADCs where exposure drives adverse events.","rationale":"Flat dosing of checkpoint inhibitors was justified by PK modelling, not by outcome trials; for ADCs, exposure-related toxicities (neuropathy, interstitial lung disease, ocular events) argue for tighter exposure control.","test":"Two randomised PK-and-outcome trials, one checkpoint inhibitor and one ADC, comparing flat with weight-banded dosing, with tolerability and cost as key secondaries.","maturity":"early-clinical","actor":"payer","cost":"medium","horizonYears":3},{"id":"idea-tr1-intermittent-dosing-to-delay-resistance","kind":"idea","name":"Test intermittent dosing of targeted drugs to delay resistance, with honest priors","aka":[],"tldr":"Giving a targeted drug in pulses rather than continuously might slow the emergence of resistant cells and reduce side effects. Early results are mixed, so this needs careful trials with clear rules for when to try it.","summary":"Randomised trials of intermittent versus continuous dosing of targeted agents, selected by biology: intermittent schedules are favoured where preclinical data show drug-addicted resistant clones (as in some BRAF-mutant melanoma models) or where toxicity is exposure-driven; disfavoured where continuous suppression is needed. The SWOG S1320 trial found intermittent BRAF/MEK inhibition did not improve PFS in melanoma, so the proposal targets settings with stronger mechanistic support (e.g., some hormonal and ALK-driven settings) and uses ctDNA to define pulse timing.","asOf":"2026-09-08","links":[{"label":"SWOG S1320 (intermittent vs continuous dabrafenib and trametinib) on ClinicalTrials.gov","url":"https://clinicaltrials.gov/study/NCT02196181"}],"tags":[],"related":[],"cancers":["melanoma","nsclc"],"sections":[],"technologies":["kinase-inhibitors"],"targets":["braf","alk"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["resistance","ctdna"],"trials":["alex","cobrim","columbus","combi-ad","combi-d"],"people":[],"bottlenecks":["b-dose-optimisation","b-resistance"],"keyPapers":["paper-chapman-vemurafenib-nejm-2011","paper-braf-melanoma-n-engl-j-med-2015","paper-alk-nsclc-n-engl-j-med-2013"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"In biologically selected settings, intermittent schedules will achieve non-inferior PFS with reduced toxicity and cost, and in a subset will delay resistance; in unselected settings they will not.","rationale":"Resistance is an evolutionary process sensitive to dosing schedule; preclinical models show schedule-dependent outcomes, but the one large clinical test was negative, so selection criteria matter.","test":"Two randomised phase 2 trials in settings with preclinical support for drug-addicted resistance, with ctDNA-guided pulse timing and PFS non-inferiority plus toxicity as endpoints.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":4},{"id":"idea-cost-low-dose-immunotherapy-trials","kind":"idea","name":"Test one-tenth-dose immunotherapy where the full dose is unaffordable","aka":[],"tldr":"A randomised trial at Tata Memorial added nivolumab at 20 mg every three weeks, about one-twelfth of the standard dose, to cheap metronomic chemotherapy for head and neck cancer patients who could not afford full-dose immunotherapy, and they lived longer. Checkpoint inhibitors saturate their target far below approved doses, so publicly funded trials should test low doses in common cancers.","summary":"Patil et al. (JCO 2023) randomised 151 patients with advanced head and neck cancer to triple metronomic chemotherapy with or without nivolumab 20 mg flat dose every three weeks, about one-twelfth of the standard dose. One-year overall survival was 43.4% versus 16.3%. Checkpoint inhibitors saturate their target at doses far below those approved, which were chosen for development convenience rather than minimum effective exposure. Publicly funded non-inferiority trials of low-dose pembrolizumab and nivolumab in common indications would establish whether the finding generalises.","asOf":"2026-09-10","links":[{"label":"Patil et al., JCO 2023: low-dose nivolumab with metronomic chemotherapy","url":"https://doi.org/10.1200/JCO.22.01015"}],"tags":[],"related":[],"cancers":["head-and-neck"],"sections":["immunotherapy"],"technologies":["checkpoint-inhibitor"],"targets":[],"drugs":["nivolumab","pembrolizumab"],"companies":[],"institutions":["tata-memorial"],"pathways":[],"terms":["project-optimus"],"trials":["checkmate-141","keynote-048","keynote-412","keynote-689","nivopostop"],"people":[],"bottlenecks":["b-dose-optimisation","b-global-access","b-drug-pricing"],"keyPapers":["paper-keynote-048-lancet-2019","paper-jean-pascal-machiels-lancet-2019","paper-pembrolizumab-head-and-neck-j-clin-oncol-2017"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"In at least two common indications, a checkpoint inhibitor dose of 10% to 25% of the labelled dose will be non-inferior for overall survival at two years, at less than a quarter of the drug cost.","rationale":"Receptor occupancy data from the original phase 1 trials showed saturation at low doses; Project Optimus now requires sponsors to justify doses, but only for new drugs.","test":"Publicly or philanthropically funded randomised non-inferiority trials in India, Brazil and Africa, with pharmacokinetic sub-studies and survival as the endpoint.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":4},{"id":"idea-bio2-protein-plus-training-during-io","kind":"idea","name":"Test protein and resistance training during immunotherapy","aka":[],"tldr":"Muscle is an immune organ as well as a movement organ. Building it during immunotherapy might improve how well the treatment works, not just how patients feel.","summary":"Muscle secretes myokines including interleukin-15 and irisin that affect immune cell function, and low muscle mass is associated with poorer checkpoint inhibitor outcomes in several retrospective series. Whether that association is causal or simply reflects disease burden is unknown, and a randomised exercise and protein intervention during checkpoint therapy would answer it while also improving function.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Cachexia, toxicity and the limits of the patient): Fearon et al., Definition and classification of cancer cachexia (Lancet Oncology 2011)","url":"https://doi.org/10.1016/S1470-2045(10)70218-7"}],"tags":[],"related":["idea-exercise-as-adjuvant"],"cancers":["melanoma","nsclc","rcc"],"sections":[],"technologies":["exercise-oncology","checkpoint-inhibitor"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-cachexia-supportive","b-immunotherapy-response","b-tme-immunosuppression"],"keyPapers":["paper-fearon-lancet-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Supervised resistance training with protein supplementation during checkpoint blockade improves progression-free survival or response rate compared with usual care, mediated by measurable changes in circulating immune cell phenotype.","rationale":"Exercise increases natural killer cell mobilisation and alters myeloid phenotype in humans, and mouse studies show exercise-dependent improvements in tumour immune control. The intervention has no toxicity and independent quality-of-life benefit, so the trial is low-risk.","test":"A randomised trial in patients starting checkpoint blockade with response and immune profiling co-primary endpoints, powered pragmatically and embedded in routine care.","maturity":"speculative","actor":"research","cost":"medium","horizonYears":5},{"id":"idea-tr2-marker-stratified-default","kind":"idea","name":"Test the drug in biomarker-negative patients too, so the biomarker can be validated","aka":[],"tldr":"Trials that only enrol patients with a positive biomarker can never prove the biomarker matters. Including a smaller biomarker-negative group would show whether the test is really needed.","summary":"Enrichment designs enrol only biomarker-positive patients and cannot estimate the interaction between marker and treatment. Marker-stratified designs (all-comers with stratified randomisation and pre-specified interaction tests) are the accepted way to validate a predictive biomarker but are rarely used because they cost more. Regulators could require a marker-negative cohort (even under-powered but pooled across trials) whenever a biomarker is proposed to restrict a label, so the restriction is evidence-based.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Biomarkers are not validated or standardised): Fernandez et al., Examination of low ERBB2 protein expression in breast cancer tissue (JAMA Oncology 2022)","url":"https://doi.org/10.1001/jamaoncol.2021.7239"}],"tags":[],"related":["hrd","her2-low","idea-tr2-biomarker-negative-arms"],"cancers":[],"sections":[],"technologies":["companion-diagnostic"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["companion-diagnostic-term","hazard-ratio"],"trials":[],"people":[],"bottlenecks":["b-biomarker-validation","b-trial-design"],"keyPapers":["paper-fernandez-jama-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Among drugs approved with a biomarker restriction, marker-negative cohorts will show clinically meaningful benefit in at least a fifth of cases, revealing that current enrichment designs deny treatment to patients who would benefit.","rationale":"PD-L1 cut-offs, HER2-low, and HRD have each shifted after post hoc analyses of marker-negative or unselected populations, showing that enrichment-only evidence leads to unstable labels.","test":"Fund marker-negative cohorts in five ongoing enrichment trials and analyse interaction effects; compare with historical label revisions.","maturity":"early-clinical","actor":"regulator","cost":"medium","horizonYears":4},{"id":"idea-prev-gleason6-terminology-rct","kind":"idea","name":"Test whether calling Gleason 6 'not cancer' changes what men choose","aka":[],"tldr":"Gleason 6 prostate lesions do not metastasise. A trial could show whether describing them without the word cancer leads more men to choose monitoring.","summary":"Survey experiments show terminology shifts preference; no randomised trial has tested it in real diagnoses. Propose a trial embedded in diagnostic clinics: pathology report and consultation script using 'cancer' versus 'indolent lesion of epithelial origin', with active surveillance uptake, anxiety, and two-year treatment as endpoints.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Overdiagnosis and false alarms): Welch & Black, Overdiagnosis in cancer (JNCI 2010)","url":"https://doi.org/10.1093/jnci/djq099"}],"tags":[],"related":["prostate-roadmap","idea-prostate-metastatic-presentation-as-the-screening-endpoint"],"cancers":["prostate"],"sections":["early-detection"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-overdiagnosis","b-patient-voice"],"keyPapers":["paper-welch-j-natl-cancer-inst"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Non-cancer terminology increases active surveillance uptake by at least 10 percentage points and reduces anxiety without reducing adherence to follow-up.","rationale":"The biology is settled; the behavioural question is testable at low cost.","test":"600-man RCT in five centres.","maturity":"speculative","actor":"research","cost":"small","horizonYears":2},{"id":"idea-gbc-t1b-simple-cholecystectomy-prospective-study","kind":"idea","name":"Test whether T1b gallbladder cancer needs the second operation at all","aka":[],"tldr":"Guidelines send everyone whose chance-found gallbladder cancer has just reached the muscle layer back for liver and lymph node surgery, yet the largest international series found 95 in 100 alive without the disease at five years whether or not they had it. A prospective study could spare thousands of operations, or confirm they are needed.","summary":"In 237 T1b patients from 14 centres in Korea, Japan, Chile and the United States, five-year disease-specific survival was 93.7 percent after simple cholecystectomy and 95.5 percent after extended cholecystectomy (p=0.496), with no difference by nodes or location (Kim 2018). Pawlik's series found no liver residual disease in T1 tumours but nodal metastasis in 12.5 percent. The evidence is retrospective and confounded by selection, and T1b itself is hard to standardise on pathology. A prospective registry with central pathology review, or a non-inferiority trial of observation with imaging surveillance against extended cholecystectomy, is the missing study.","asOf":"2026-09-24","links":[{"label":"Kim et al.: optimal surgical treatment of T1b gallbladder cancer, 14 centres (J Hepatobiliary Pancreat Sci 2018)","url":"https://europepmc.org/article/MED/30562839"}],"tags":["gallbladder-evidence"],"related":[],"cancers":["gallbladder"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["radical-cholecystectomy","incidental-gallbladder-cancer","tnm-staging","de-escalation"],"trials":[],"people":[],"bottlenecks":["b-trial-design","b-surgery-radiation-innovation"],"keyPapers":["paper-kim-t1b-gallbladder-cancer-international-jhbps-2018","paper-pawlik-incidental-gallbladder-cancer-residual-disease-jgs-2007"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"In T1b gallbladder cancer with negative cystic duct margin and no perforation, simple cholecystectomy with surveillance is non-inferior to extended cholecystectomy for five-year disease-specific survival, with a margin of 5 percentage points.","rationale":"Observed five-year disease-specific survival above 93 percent in both arms leaves little room for benefit; extended cholecystectomy carries operative risk and cost in an elderly population.","test":"International prospective registry with central pathology and pre-specified comparison, or a randomised non-inferiority trial (about 600 patients for a 5-point margin at 94 percent baseline) with nodal sampling as a secondary randomisation.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":8},{"id":"lymphoma-ev-the-drugs-that-cure-and-the-places-without-them","kind":"idea","name":"The drugs that cure lymphoma, and the places that do not have them","aka":["Global access to rituximab and asparaginase","Lymphoma treatment access"],"tldr":"Lymphoma is among the most curable common cancers where the drugs exist. Rituximab is thirty years old and still out of reach for many of the people who need it.","summary":"The counter-argument is that drug supply without pathology, imaging, supportive care and a haematologist does not cure anyone, and that is correct: Burkitt lymphoma treatment requires management of tumour lysis syndrome, and diffuse large B-cell lymphoma requires growth factor support and infection management. That makes the programme a health-system intervention rather than a drug donation, which is the form these things have to take to work.","asOf":"2026-10-01","links":[],"tags":["lymphoma-evidence"],"related":["lymphoma-roadmap"],"cancers":["burkitt-lymphoma","dlbcl","non-hodgkin-lymphoma","peripheral-t-cell-lymphoma","hodgkin-lymphoma"],"sections":["chemotherapy","immunotherapy","supportive-care"],"technologies":[],"targets":[],"drugs":["rituximab","asparaginase","cyclophosphamide","doxorubicin","vincristine","prednisone"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-global-access","b-drug-pricing","b-workforce","b-care-fragmentation"],"keyPapers":["paper-burkitt-sarcoma-involving-jaws-african-children-br-j-surg-1958","paper-smile-chemotherapy-nk-t-cell-lymphoma-jco-2011","paper-hesseling-pediatr-blood-cancer"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Securing reliable supply of a short list of off-patent and biosimilar lymphoma drugs, led by rituximab and asparaginase, would save more lives from lymphoma over the next decade than any new agent now in development.","rationale":"Rituximab was approved in 1997 and biosimilars have been available for years, yet supply remains intermittent in much of Africa, south Asia and Latin America. Asparaginase is the drug that makes extranodal NK/T-cell lymphoma treatable, and it is subject to recurrent global shortages. Burkitt lymphoma, which is curable with chemotherapy alone in a high proportion of children, is concentrated in the equatorial African belt where Burkitt first described it. The arithmetic favours supply over discovery.","test":"A costed procurement and supply programme for a defined lymphoma drug list in a set of countries, with pre-specified measurement of one-year overall survival in Burkitt lymphoma, diffuse large B-cell lymphoma and extranodal NK/T-cell lymphoma before and after, against comparator regions without the programme.","maturity":"speculative","actor":"policy","cost":"medium","horizonYears":6},{"id":"idea-tr1-pathology-triggered-referral","kind":"idea","name":"The pathology lab triggers a trial referral the day a rare cancer is diagnosed","aka":[],"tldr":"The pathologist is the first person to know a cancer is rare or has a targetable marker. A rule in the lab system could notify a trial team at that moment, before treatment decisions close the window.","summary":"Laboratory information systems flag defined diagnoses (rare histologies, MSI-high, NTRK fusion, specific paediatric-type tumours in adults) and send a structured notification to a regional trial coordination office and the treating clinician, with matched trials attached. Consent-to-contact rules govern direct patient contact. Precedents exist in stroke and sepsis alerting; oncology pathology alerting has been used for HER2 and MSI testing completeness.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Trials enrol too few, too slowly): Unger et al., Systematic review of barriers to cancer trial participation (JNCI 2019)","url":"https://doi.org/10.1093/jnci/djy221"}],"tags":[],"related":[],"cancers":["sarcoma","neuroendocrine"],"sections":[],"technologies":["histopathology-ihc","digital-pathology-ai"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["msi","gene-fusion","first-line"],"trials":[],"people":[],"bottlenecks":["b-trial-enrolment","b-rare-cancers"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Pathology-triggered referral will increase the proportion of patients with the flagged diagnoses seen by a trial team before first-line treatment, and enrolment in first-line trials for those diagnoses.","rationale":"For many rare cancers the only trial is first-line; once standard chemotherapy starts, the patient is ineligible. Diagnosis-time alerting acts before the window closes.","test":"Implement in one regional pathology network for five diagnoses; compare pre-treatment trial-team contact rate and first-line trial enrolment with neighbouring regions.","maturity":"speculative","actor":"clinic","cost":"small","horizonYears":2},{"id":"idea-reg-new-indication-exclusivity-off-patent","kind":"idea","name":"Three years of indication-specific exclusivity for proving a new cancer use of an old drug","aka":[],"tldr":"Nobody funds trials of old drugs because competitors can sell the result for free. A short exclusive period for the new use, like the one given for children's studies, would change that.","summary":"Paediatric exclusivity in the US and the EU's one-year data protection for a new indication of a well-established substance show that time-limited rewards can induce trials on old drugs. For oncology repurposing the reward is too weak to matter. The proposal is a three-year indication-specific exclusivity (marketing protection for the new oncology indication, with the drug remaining generic for existing uses) granted to any sponsor, including generic manufacturers and non-profits, that obtains approval of a new oncology indication for an off-patent drug on the basis of an adequately powered trial, with a price ceiling for the new indication tied to the trial cost.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (No incentive to repurpose cheap drugs): Pantziarka et al., The Repurposing Drugs in Oncology (ReDO) Project (ecancer 2014)","url":"https://doi.org/10.3332/ecancer.2014.442"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-generic-repurposing","b-incentive-misalignment"],"keyPapers":["paper-pantziarka-ecancermedicalscience"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"The reward induces at least ten new registered phase 3 oncology trials of off-patent drugs within five years, sponsored by generic companies or non-profits, without materially raising prices for existing uses.","rationale":"Generic manufacturers have the manufacturing and regulatory capacity to sponsor trials but no way to recoup the cost; a modest, indication-limited exclusivity is a more targeted incentive than transferable vouchers and has precedent in paediatric legislation.","test":"Legislate the reward in one jurisdiction and count new repurposing trial registrations with generic or non-profit sponsors against the prior five years.","maturity":"speculative","actor":"policy","cost":"small","horizonYears":5},{"id":"idea-cost-value-scale-in-coverage","kind":"idea","name":"Tie coverage and copays to the ESMO benefit scale","aka":[],"tldr":"Oncology has two respected scales that grade how much a drug helps in each indication; payers could set low copays for high-grade uses and require a conversation for low-grade ones instead of blanket prior authorisation.","summary":"The ESMO Magnitude of Clinical Benefit Scale grades each indication from 1 to 5 (palliative) or A to C (curative); the ASCO Value Framework produces a net health benefit score; ICER publishes cost-effectiveness reviews. Value-based insurance design lowers cost sharing for high-value care. Applying the scales to oncology formularies (zero copay for ESMO-MCBS 4 and 5 indications, standard review for 1 and 2) would target scrutiny where benefit is smallest and remove it where the case is clear, without any payer inventing its own scoring.","asOf":"2026-09-10","links":[{"label":"ESMO-MCBS","url":"https://www.esmo.org/guidelines/esmo-mcbs"},{"label":"ICER","url":"https://icer.org/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["esmo","asco"],"pathways":[],"terms":["icer-value-assessment"],"trials":[],"people":[],"bottlenecks":["b-drug-pricing","b-incentive-misalignment","b-knowledge-diffusion"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Value-tiered oncology formularies will cut prior authorisation volume for high-benefit indications by more than 80% and shift prescribing away from ESMO-MCBS grade 1 and 2 indications without reducing use of grade 4 and 5 treatments.","rationale":"The scales are public, peer-reviewed and updated; using them costs a payer nothing and is more defensible than proprietary criteria.","test":"A payer pilot applying value tiers to checkpoint inhibitor and targeted therapy indications, measuring approvals, prescribing by grade, spend and appeals.","maturity":"early-clinical","actor":"payer","cost":"small","horizonYears":2},{"id":"idea-acc-eml-listing-price-commitments","kind":"idea","name":"Tie WHO essential-medicines listing to a published tiered price and supply pledge","aka":[],"tldr":"When a cancer drug is added to the WHO essential medicines list, the maker should publicly commit to a low price and reliable supply for poorer countries, or the listing is withheld.","summary":"Listing on the WHO Model List of Essential Medicines is a reputational asset for manufacturers but carries no obligation. Many listed cancer medicines (trastuzumab, imatinib, rituximab) remained unaffordable or unavailable in most low-income countries for years after listing. The proposal is that the Expert Committee request, as part of the application, a public tiered-price schedule and a minimum supply commitment for low- and lower-middle-income countries, and publish which applicants declined.","asOf":"2026-09-08","links":[{"label":"WHO Model Lists of Essential Medicines","url":"https://www.who.int/groups/expert-committee-on-selection-and-use-of-essential-medicines/essential-medicines-lists"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":["trastuzumab","imatinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-global-access","b-drug-pricing"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Within three years of a linkage policy, the median public-sector price of newly listed cancer medicines in low-income countries will fall by at least half relative to the pre-policy trajectory, and stock-out reports will decline.","rationale":"Naming-and-shaming works when the audience cares: the same companies publish access-to-medicine indices and lobby for EML listing. Vaccines show that price transparency plus volume commitments reshapes markets.","test":"Pilot with the next EML review cycle: require voluntary disclosure, publish who complied, and track price and availability through the WHO/Health Action International medicine price surveys.","maturity":"speculative","actor":"policy","cost":"small","horizonYears":3},{"id":"idea-til-guided-deescalation","kind":"idea","name":"TIL-based omission of chemotherapy in stage I TNBC","aka":[],"tldr":"Small triple-negative tumours packed with immune cells almost never come back. The idea is to skip chemotherapy for those patients.","summary":"Small triple-negative tumours packed with immune cells almost never come back, so this idea skips chemotherapy for stage I TNBC with high stromal TILs and treats with surgery and radiation alone. TILs mark a tumour already under immune control, and pooled cohorts such as ETNA, OPTimal and TIL-CHOICE suggest chemotherapy adds toxicity without measurable benefit in this group. A prospective single-arm trial with a non-inferiority boundary, central AI-assisted TIL scoring and ctDNA surveillance as a safety net would be needed before practice changes. The idea is being tested at scale, draws on histopathology and digital pathology AI, and is linked from the idea Payer-funded trials that omit surgery or radiotherapy in low-risk patients.","asOf":"2026-09-04","links":[{"label":"Leon-Ferre et al., Tumour-infiltrating lymphocytes in triple-negative breast cancer treated without chemotherapy (JAMA 2024)","url":"https://doi.org/10.1001/jama.2024.3056"}],"tags":[],"related":[],"cancers":["tnbc"],"sections":[],"technologies":["histopathology-ihc","digital-pathology-ai"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["tils"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-leon-ferre-tils-tnbc-no-chemotherapy-jama-2024"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Stage I TNBC with sTILs ≥50% (or ≥30% with pT1a-b) managed with surgery and radiation alone has 5-year iDFS non-inferior to chemotherapy.","rationale":"TILs mark a tumour already under immune control; chemotherapy adds toxicity without measurable benefit in this group.","test":"Run a single-arm prospective trial with a non-inferiority boundary (e.g., 5-year iDFS >90%), central AI-assisted TIL scoring, and ctDNA surveillance as a safety net.","maturity":"being-tested-at-scale"},{"id":"idea-bio1-immunopeptidome-timing","kind":"idea","name":"Time immunotherapy to the moment targeted drugs make tumours visible","aka":[],"tldr":"Targeted drugs briefly make cancer cells easier for the immune system to spot. Giving immunotherapy exactly in that window, rather than at the same time, may work better.","summary":"MAPK and CDK4/6 inhibition transiently increase MHC class I expression, antigen presentation and interferon signalling, then this fades as resistance develops. Concurrent combinations have often been toxic and no more effective. Mass spectrometry immunopeptidomics and MHC imaging could define the window in patients, and immunotherapy could be scheduled to coincide with peak presentation rather than dosed continuously alongside.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Acquired resistance to every therapy): Soria et al., Osimertinib in untreated EGFR-mutated NSCLC (FLAURA, NEJM 2018)","url":"https://doi.org/10.1056/NEJMoa1713137"}],"tags":[],"related":[],"cancers":["melanoma","breast-hr-positive"],"sections":[],"technologies":["checkpoint-inhibitor","proteomics","cdk46-inhibitor"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["ras-mapk","pd1-checkpoint"],"terms":[],"trials":[],"people":[],"bottlenecks":["b-resistance","b-immunotherapy-response","b-combination-space"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Immunotherapy administered during the measured peak of antigen presentation after targeted therapy produces greater T-cell infiltration and deeper responses than concurrent continuous combination, with less toxicity.","rationale":"The immunomodulatory effect of targeted agents is transient and dose-dependent; scheduling is a free variable that combination trials have almost never explored systematically.","test":"Serial biopsy window study mapping MHC class I and immunopeptidome dynamics over the first weeks of targeted therapy, then a randomised schedule comparison in the tumour type with the clearest window.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":5},{"id":"idea-tr1-ttf-and-qol-coprimary","kind":"idea","name":"Time to treatment failure and quality of life as co-primary endpoints in non-curative trials","aka":[],"tldr":"For treatments that will not cure, what matters is how long the treatment keeps working without becoming unbearable, and how the person feels. Trials should measure both of those as their main results.","summary":"In palliative-intent settings, trials adopt time to treatment failure (progression, death or discontinuation for toxicity or patient choice) together with a validated QoL instrument (EORTC QLQ-C30 or disease module) analysed as time to definitive deterioration, as co-primary endpoints, with OS as the principal secondary endpoint. PFS alone rewards drugs that delay scan progression while making patients feel worse.","asOf":"2026-09-08","links":[{"label":"EORTC Quality of Life Group (QLQ-C30)","url":"https://qol.eortc.org/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["curie-nki-eortc"],"institutions":[],"pathways":[],"terms":["pfs","os"],"trials":[],"people":[],"bottlenecks":["b-trial-design","b-toxicity-qol","b-patient-voice"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Trials with TTF plus QoL co-primaries will more often identify regimens that patients continue and prefer, and drugs approved on these endpoints will show better real-world persistence than drugs approved on PFS alone.","rationale":"Discontinuation for toxicity is common with modern combinations and invisible in PFS. Regulators have accepted QoL-based labels in some settings; the co-primary structure protects against approving effective-but-intolerable regimens.","test":"Re-analyse completed phase 3 trials with available PRO data under the co-primary framework and identify decisions that would have changed; then run a prospective trial in a common palliative setting with the new endpoints.","maturity":"speculative","actor":"regulator","cost":"small","horizonYears":3},{"id":"idea-tr2-timestamped-eln","kind":"idea","name":"Time-stamped electronic lab notebooks submitted with the paper","aka":[],"tldr":"Electronic notebooks record when each experiment was done and what the raw result was. Submitting them with the paper would show whether the analysis was planned or fitted after the fact.","summary":"Electronic lab notebooks are widespread but their audit trails are never shared. Submitting a cryptographically time-stamped export of the relevant notebook entries (or hashes anchored to a public ledger at the time of the experiment) with a manuscript would let reviewers verify the sequence of hypotheses, experiments and analyses, and would deter post hoc rationalisation.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Preclinical results do not reproduce): Errington et al., Investigating the replicability of preclinical cancer biology (eLife 2021)","url":"https://doi.org/10.7554/eLife.71601"}],"tags":[],"related":["idea-tr2-raw-image-deposit","idea-tr2-preclinical-registered-reports"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-reproducibility"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Papers with notebook audit trails will show fewer discrepancies between planned and reported analyses and will be corrected or retracted less often.","rationale":"Regulated industry research already operates under such audit trails (21 CFR Part 11); academia has the tools but not the norm.","test":"Pilot voluntary submission at one journal with reviewer access; survey reviewers on utility; compare discrepancy rates.","maturity":"speculative","actor":"engineering","cost":"small","horizonYears":2},{"id":"idea-moon-toxicity-first-endpoints","kind":"idea","name":"Tolerability as a co-primary endpoint with its own label claim","aka":[],"tldr":"New cancer drugs should have to prove not only that they extend life but how they affect how people feel and function, with that result printed in the label like efficacy.","summary":"Trials are powered on progression or survival; tolerability is described from clinician-graded adverse events and rarely tested as a hypothesis. The proposal is a regulatory framework in which a pre-specified patient-reported tolerability endpoint (e.g., PRO-CTCAE composite or physical function decline) can be co-primary or a formal secondary endpoint eligible for a label claim, with the analysis methods (time to deterioration, area under the curve, cumulative burden) standardised by regulators and academic groups such as SISAQOL-IMI.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Toxicity and quality of life are undervalued): Di Maio et al., Symptomatic toxicities experienced during anticancer treatment: agreement between patient and physician reporting (JCO 2015)","url":"https://doi.org/10.1200/JCO.2014.57.9334"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["irae","pfs"],"trials":[],"people":[],"bottlenecks":["b-toxicity-qol","b-trial-design"],"keyPapers":["paper-di-maio-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Once tolerability claims are obtainable, sponsors will design better-tolerated regimens and doses; within five years a third of new approvals will carry a tolerability claim and median grade 3+ adverse event rates in pivotal trials will fall.","rationale":"What can be claimed gets optimised. Regulators already accept PRO-based claims outside oncology; the analytic standards now exist.","test":"Regulator issues guidance and grants the first claims; track the proportion of pivotal protocols with powered tolerability endpoints and adverse event rates over five years against the preceding five.","maturity":"early-clinical","actor":"regulator","cost":"small","horizonYears":4},{"id":"idea-tr2-two-lab-rule","kind":"idea","name":"Top journals require an independent lab to reproduce key findings before publication","aka":[],"tldr":"For the biggest claims, journals would require that a second, independent laboratory repeated the central experiment before the paper is accepted.","summary":"Some fields (particle physics with independent detectors, genome-wide association studies with replication cohorts) require independent confirmation as a condition of publication. Cancer biology does not. Top journals could require, for papers whose central claim is a therapeutic effect in a model system, that an independent lab (declared, without shared authorship interests) reproduce the key experiment, with the replication reported in the paper.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Preclinical results do not reproduce): Errington et al., Investigating the replicability of preclinical cancer biology (eLife 2021)","url":"https://doi.org/10.7554/eLife.71601"}],"tags":[],"related":["idea-tr2-multilab-preclinical","idea-tr2-replication-before-ind"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-reproducibility"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Papers published under the rule will replicate in subsequent independent studies at more than twice the rate of comparable papers published without it.","rationale":"Genome-wide association studies were plagued by false positives until replication cohorts became mandatory, after which findings became highly reliable.","test":"One high-impact journal adopts the rule for therapeutic claims; track replication outcomes of the first 50 papers against matched papers elsewhere.","maturity":"speculative","actor":"policy","cost":"small","horizonYears":3},{"id":"idea-total-body-pet-dosimetry","kind":"idea","name":"Total-body PET for personalised radioligand dosing","aka":[],"tldr":"Ultra-sensitive whole-body scanners can measure exactly where a radioactive drug goes at tiny tracer doses, allowing each patient's therapeutic dose to be tailored.","summary":"Radioligand therapy is given at fixed activity despite wide variation in tumour and kidney dose, so this idea uses ultra-sensitive total-body PET with 44Sc- or 89Zr-labelled analogues to measure each patient's pharmacokinetics before treatment and tailor the therapeutic dose. Dosimetry-guided prescription of 177Lu-PSMA is expected to raise tumour absorbed dose and response without exceeding kidney and marrow limits. Personalised dosimetry is established in radioiodine and SIRT, and total-body scanners from United Imaging and Siemens Healthineers remove the imaging-time and dose barriers. The test is a randomised trial of dosimetry-guided versus fixed-dose Pluvicto in prostate cancer with PSA50 and rPFS endpoints. At early-clinical maturity it addresses the bottleneck Wrong doses.","asOf":"2026-09-04","links":[{"label":"VISION: lutetium-177 PSMA-617 radioligand therapy extends survival in advanced prostate cancer (New England Journal of Medicine 2021)","url":"https://doi.org/10.1056/NEJMoa2107322"}],"tags":[],"related":[],"cancers":["prostate"],"sections":[],"technologies":["pet-ct","radioligand-therapy","spect"],"targets":[],"drugs":["pluvicto"],"companies":["united-imaging","siemens-healthineers"],"institutions":[],"pathways":[],"terms":["dosimetry"],"trials":["nct06004661","psmaddition","psmafore","therap","vision"],"people":[],"bottlenecks":[],"keyPapers":["paper-lutetium-177-vipivotide-tetrax-prostate-oncol-ther-2025","paper-lutetium-177-vipivotide-tetrax-prostate-journal-2023"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Dosimetry-guided activity prescription for 177Lu-PSMA increases tumour absorbed dose and response without exceeding kidney and marrow limits, compared with fixed 7.4 GBq.","rationale":"Established in radioiodine and SIRT; total-body PET removes the imaging-time and dose barriers to pre-therapy dosimetry.","test":"Randomised dosimetry-guided vs fixed-dose Pluvicto trial with PSA50 and rPFS endpoints.","maturity":"early-clinical"},{"id":"idea-data-toxicity-cds-for-nurses","kind":"idea","name":"Toxicity-management decision support for nurses and pharmacists","aka":[],"tldr":"Give the nurses and pharmacists who take patients' calls a tool that walks them through recognising and managing side effects of modern cancer drugs, including when to escalate.","summary":"Immunotherapy and targeted therapy toxicities are managed by triage nurses and pharmacists who may see a given drug rarely. Guideline-based toxicity algorithms (ESMO, ASCO, SITC) exist as tables. Encoding them as decision support integrated with ePRO alerts, with drug-specific pathways and escalation triggers, would standardise management and shorten time to steroids or hospital review for serious immune-related events.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Knowledge reaches practice too slowly): Morris, Wooding & Grant, The answer is 17 years, what is the question (JRSM 2011)","url":"https://doi.org/10.1258/jrsm.2011.110180"}],"tags":[],"related":["idea-data-pro-as-structured-standard"],"cancers":[],"sections":["ai-computation","supportive-care"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["irae","crs"],"trials":[],"people":[],"bottlenecks":["b-knowledge-diffusion","b-toxicity-qol","b-workforce"],"keyPapers":["paper-morris-j-r-soc-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Toxicity CDS will reduce time from symptom report to appropriate management and cut hospital admissions for grade 3 or higher immune-related adverse events by a meaningful margin.","rationale":"Delayed recognition of immune-related adverse events is a documented cause of morbidity; nurse-led triage with structured pathways has reduced admissions in single-centre studies.","test":"Deploy across a cancer network's triage lines for one year; compare admissions for immune-related events and time to intervention with the prior year and matched networks.","maturity":"early-clinical","actor":"clinic","cost":"small","horizonYears":2},{"id":"idea-bio1-methylation-clone-tracking","kind":"idea","name":"Track clones in blood with methylation patterns instead of mutations","aka":[],"tldr":"Tumour DNA in blood can be told apart by chemical marks as well as mutations. Marks are more numerous and cheaper to read, so they could track more sub-populations for less money.","summary":"Mutation-based clone tracking needs deep whole-exome or genome sequencing of tumour and plasma. Methylation haplotypes are clone-stable, abundant, and readable with targeted enrichment at lower cost. The proposal is to define clone-specific methylation haplotypes from multi-region tumour tissue and monitor their plasma fractions as a low-cost clonal evolution assay.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Tumour heterogeneity and clonal evolution): Gerlinger et al., Intratumor heterogeneity and branched evolution (NEJM 2012)","url":"https://doi.org/10.1056/NEJMoa1113205"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["methylation-profiling","liquid-biopsy"],"targets":[],"drugs":[],"companies":["grail"],"institutions":[],"pathways":[],"terms":["ctdna"],"trials":[],"people":[],"bottlenecks":["b-tumor-heterogeneity"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Methylation-haplotype clone tracking recapitulates mutation-defined clonal dynamics in plasma with at least 80 percent concordance at a fifth of the sequencing cost.","rationale":"Methylation is used for cancer signal origin in multi-cancer detection tests and is clonally heritable; epiallele heterogeneity has been shown to track evolution in leukaemias.","test":"Paired analysis on 50 patients with existing multi-region WGS and serial plasma: derive methylation clone markers and compare trajectories with the mutation-based phylogenies.","maturity":"speculative","actor":"research","cost":"small","horizonYears":3},{"id":"idea-moon-clinician-creator-programme","kind":"idea","name":"Train and fund oncology clinicians as public content creators","aka":[],"tldr":"Give oncologists and cancer nurses the training, time and production support to reach people where they actually get information, on social video and podcasts.","summary":"The most-viewed cancer content is produced by non-experts; clinicians who do communicate publicly do so unpaid and untrained. The proposal is a fellowship programme: media training, protected time, production support, legal and ethical guidance, and a shared network for coordinated messaging, with metrics on reach among target audiences and displacement of misinformation.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Misinformation and unproven therapies): Johnson et al., Cancer misinformation and harmful information on Facebook and other social media (JNCI 2022)","url":"https://doi.org/10.1093/jnci/djab141"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-misinformation","b-workforce"],"keyPapers":["paper-johnson-j-natl-cancer-inst"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A cohort of fifty funded clinician creators reaches audiences comparable to leading misinformation accounts within two years and measurably improves knowledge on tested topics among viewers.","rationale":"Trust in individual clinicians remains high even where trust in institutions is low; format and reach, not credibility, are the deficits.","test":"Fund a first cohort; compare reach and audience-survey knowledge against a baseline of institutional channels and against misinformation accounts on the same topics.","maturity":"early-clinical","actor":"philanthropy","cost":"small","horizonYears":2},{"id":"idea-acc-serious-illness-conversation-prompts","kind":"idea","name":"Train every oncology team in serious-illness conversations and prompt them in the record","aka":[],"tldr":"Patients with advanced cancer often never have a clear conversation about what to expect and what matters to them. A structured conversation guide, taught to clinicians and prompted by the record, makes these talks happen earlier.","summary":"The Serious Illness Care Program (Ariadne Labs) combines clinician training in a structured conversation guide with electronic prompts and documentation. A cluster-randomised trial in oncology showed earlier, more frequent, and more patient-centred conversations and reduced anxiety and depression. Adoption remains limited. Making the programme a standard component of oncology practice would improve goal-concordant care at low cost.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Pain relief and palliative care are unavailable to most): WHO fact sheet, Palliative care","url":"https://www.who.int/news-room/fact-sheets/detail/palliative-care"}],"tags":[],"related":[],"cancers":[],"sections":["supportive-care"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-palliative","b-patient-voice"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Systematic implementation will raise the proportion of patients with advanced cancer who have a documented goals-of-care conversation before their last month of life from under 40% to above 80%, and reduce non-beneficial intensive care at end of life.","rationale":"Trial evidence exists; the intervention is training and prompts, which scale cheaply.","test":"A stepped implementation across a health system with conversation documentation timing, end-of-life care intensity, and bereaved family ratings as endpoints.","maturity":"being-tested-at-scale","actor":"clinic","cost":"small","horizonYears":2},{"id":"idea-bio2-trained-immunity-priming","kind":"idea","name":"Train the bone marrow to make better anti-tumour immune cells","aka":[],"tldr":"Certain vaccines and fungal sugars reprogramme the bone marrow so it produces more aggressive immune cells for months. That could be used before immunotherapy.","summary":"Trained immunity (epigenetic reprogramming of haematopoietic progenitors by BCG or beta-glucan) produces durable changes in myeloid output and reduced tumour growth in mouse models, and BCG's efficacy in bladder cancer is the oldest immunotherapy in use. Priming the marrow before checkpoint therapy or cell therapy is a cheap, generic intervention that has never been formally tested in solid tumours.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Cold tumours and the immunosuppressive microenvironment): Haslam & Prasad, Estimation of the percentage of US patients eligible for and responding to checkpoint inhibitors (JAMA Netw Open 2019)","url":"https://doi.org/10.1001/jamanetworkopen.2019.2535"}],"tags":[],"related":[],"cancers":["urothelial","colorectal"],"sections":[],"technologies":["bcg-and-intravesical-therapy","checkpoint-inhibitor"],"targets":[],"drugs":["bcg-intravesical"],"companies":[],"institutions":[],"pathways":[],"terms":["cold-vs-hot"],"trials":[],"people":[],"bottlenecks":["b-tme-immunosuppression","b-generic-repurposing"],"keyPapers":["paper-haslam-jama-netw-open"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Systemic beta-glucan or BCG priming before checkpoint blockade shifts circulating monocyte epigenetic and functional profiles and increases response rates in cold tumours.","rationale":"The mechanism operates upstream, on progenitor cells, so it could change the whole myeloid compartment rather than one tumour. Both priming agents are cheap, widely available and have decades of safety data.","test":"A randomised window trial measuring monocyte functional and epigenetic reprogramming after priming, with tumour myeloid composition on biopsy as the mechanistic endpoint before any efficacy trial.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":8},{"id":"idea-moon-patient-community-moderators","kind":"idea","name":"Trained moderators with evidence tools in online patient communities","aka":[],"tldr":"Online patient groups are where much cancer advice is exchanged. Fund and train moderators, with quick access to reliable evidence, to keep those spaces accurate and kind.","summary":"Facebook groups, forums and messaging groups are primary information sources for many patients and are where unproven therapies spread peer to peer. The proposal is a programme funding patient organisations to train volunteer moderators in evidence appraisal and compassionate correction, provide them with a rapid clinician back-channel and a curated evidence library, and measure the prevalence of unproven claims in moderated versus unmoderated groups.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Misinformation and unproven therapies): Johnson et al., Cancer misinformation and harmful information on Facebook and other social media (JNCI 2022)","url":"https://doi.org/10.1093/jnci/djab141"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-misinformation","b-patient-voice"],"keyPapers":["paper-johnson-j-natl-cancer-inst"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Trained moderation reduces the prevalence and persistence of unproven therapy claims in participating communities by half without reducing engagement.","rationale":"Peers are trusted; equipping them beats external correction. Online communities in other health areas have shown moderation shifts norms.","test":"Randomise willing communities to the programme or waitlist; content analysis of claims and engagement over six months.","maturity":"early-clinical","actor":"philanthropy","cost":"small","horizonYears":1},{"id":"idea-fund-conditional-transferable-voucher","kind":"idea","name":"Transferable priority vouchers for first-in-class drugs, with price conditions","aka":[],"tldr":"Reward companies that deliver a genuinely new kind of cancer drug with a sellable voucher for faster review of another product, but only if they agree to fair pricing and global access.","summary":"Extend the US priority review voucher model (rare paediatric disease, tropical disease) to oncology first-in-class approvals that show substantial survival benefit, with two conditions attached: a price commitment (for example launch price below a value-based threshold set by an independent body) and a global access plan (tiered pricing or licensing to the Medicines Patent Pool for low- and middle-income countries). The voucher is transferable and has sold for around $100 million historically, so the reward is real but costs the public little. Regulators would need statutory authority; a pilot could run through an existing programme's criteria.","asOf":"2026-09-08","links":[{"label":"Medicines Patent Pool","url":"https://medicinespatentpool.org/"}],"tags":[],"related":["idea-fund-value-based-patent-extension","idea-fund-global-access-licensing-royalties"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["breakthrough-designation","accelerated-approval"],"trials":[],"people":[],"bottlenecks":["b-incentive-misalignment","b-drug-pricing"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A conditional oncology voucher increases the number of first-in-class oncology approvals meeting the survival threshold per decade and results in launch prices at least 20% lower for voucher-qualified drugs than for comparable unconditioned launches.","rationale":"Rare paediatric vouchers have measurably increased paediatric rare disease activity, though without price conditions; conditional rewards are standard in public procurement. Vouchers reward the outcome (approval) rather than inputs and are cheap for governments.","test":"Model uptake with industry through a regulator-convened consultation, then legislate a five-year sunset pilot and compare first-in-class filings and launch prices before and after.","maturity":"speculative","actor":"regulator","cost":"small","horizonYears":4},{"id":"idea-cost-transparent-generic-pricing","kind":"idea","name":"Transparent cost-plus pricing for every oral oncology generic","aka":[],"tldr":"Generic imatinib and abiraterone can cost patients hundreds of dollars a month through insurance yet be sold at cost plus a fixed markup by transparent pharmacies; making that the default channel for oral cancer generics would save patients and plans money.","summary":"Mark Cuban Cost Plus Drug Company publishes its acquisition cost, a 15% markup, a pharmacy fee and shipping for each drug, including oncology generics such as imatinib, abiraterone, anastrozole, letrozole and capecitabine. Prices are often far below insurance copays on specialty tiers. Payers can add such pharmacies to networks, waive the deductible for them, or use their prices as a reference in formulary tiering.","asOf":"2026-09-10","links":[{"label":"Mark Cuban Cost Plus Drug Company","url":"https://costplusdrugs.com/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":["imatinib","abiraterone","letrozole","tamoxifen"],"companies":[],"institutions":[],"pathways":[],"terms":["drug-price-transparency","financial-toxicity"],"trials":[],"people":[],"bottlenecks":["b-drug-pricing","b-generic-repurposing"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Routing oral oncology generics through transparent cost-plus pharmacies will cut patient out-of-pocket cost for those drugs by more than half for most commercially insured patients and cut plan spend.","rationale":"For old generics the acquisition cost is public and low; the gap to what patients pay is pure distribution margin.","test":"A self-insured employer pilot: offer cost-plus pharmacies as a zero-copay option for oral oncology generics and measure patient cost, plan cost and adherence against the prior year.","maturity":"being-tested-at-scale","actor":"industry","cost":"small","horizonYears":1},{"id":"idea-transplant-free-ph-all","kind":"idea","name":"Transplant-free Ph-positive ALL for MRD-negative adults","aka":[],"tldr":"If a pill plus immunotherapy makes the leukaemia undetectable, can most adults safely skip a bone-marrow transplant?","summary":"If a tyrosine kinase inhibitor plus blinatumomab renders Philadelphia chromosome-positive acute lymphoblastic leukaemia undetectable, this idea asks whether most adults can safely forgo allogeneic transplant in first remission. The hypothesis is that patients in complete molecular remission have equivalent overall survival with TKI maintenance and MRD surveillance as with transplant. The rationale is that deaths caused by the transplant itself may exceed the relapse risk it prevents, and that blinatumomab and ponatinib rescue many relapses; in D-ALBA (GIMEMA LAL2116) around half of patients were not transplanted and did well. A trial would randomise MRD-negative patients to transplant or to TKI maintenance with BCR::ABL1 PCR and pre-emptive blinatumomab; it is being tested at scale.","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT02744768: D-ALBA (GIMEMA LAL2116)","url":"https://clinicaltrials.gov/study/NCT02744768"}],"tags":[],"related":[],"cancers":["all-leukemia"],"sections":[],"technologies":["allogeneic-hsct","ngs-mrd-clonoseq"],"targets":[],"drugs":["ponatinib","blinatumomab","dasatinib"],"companies":[],"institutions":[],"pathways":[],"terms":["ph-positive-all","mrd-negative-cr"],"trials":["d-alba"],"people":[],"bottlenecks":[],"keyPapers":["paper-blinatumomab-all-leukemia-n-engl-j-med-2017","paper-blinatumomab-all-leukemia-lancet-oncol-2015","paper-pace-ponatinib-nejm-2013"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Adults with Ph+ ALL who achieve complete molecular remission after TKI + blinatumomab have equivalent OS with TKI maintenance and MRD surveillance versus allogeneic transplant in CR1.","rationale":"Transplant mortality (10-20%) may exceed the relapse risk it prevents in molecularly negative patients; blinatumomab and ponatinib rescue many relapses.","test":"A trial would randomise MRD-negative patients after induction/consolidation to transplant vs TKI maintenance with monthly BCR::ABL1 PCR and pre-emptive blinatumomab; primary endpoint OS at 3 years.","maturity":"being-tested-at-scale"},{"id":"idea-tr1-travel-lodging-in-every-budget","kind":"idea","name":"Travel, lodging and meals reimbursed as a standard line in every trial budget","aka":[],"tldr":"People should not have to pay to be in a trial. Sponsors would routinely cover travel, hotel and food costs, paid up front rather than claimed back, which is already accepted by regulators as fair rather than coercive.","summary":"Every trial budget includes a participant-cost line administered by a third party, prepaid where possible, covering travel, parking, lodging, meals and a companion. The FDA's position is that reimbursement for expenses is not undue influence. Charities such as the Lazarex Cancer Foundation have shown that covering these costs raises enrolment among low-income patients; the idea is to make sponsor funding of it universal, with ethics committees expecting it.","asOf":"2026-09-08","links":[{"label":"FDA: Payment and Reimbursement to Research Subjects","url":"https://www.fda.gov/regulatory-information/search-fda-guidance-documents/payment-and-reimbursement-research-subjects"},{"label":"Lazarex Cancer Foundation","url":"https://lazarex.org/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-enrolment","b-trial-diversity"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Trials with prepaid participant-cost coverage will enrol a larger share of patients from low-income postcodes and have lower dropout than matched trials without it.","rationale":"Out-of-pocket costs are a documented barrier and fall hardest on poorer and minority patients. Reimbursement is cheap relative to per-patient trial cost.","test":"Sponsor-level natural experiment: compare enrolment demographics and retention before and after a portfolio-wide reimbursement policy, adjusting for indication.","maturity":"being-tested-at-scale","actor":"industry","cost":"medium","horizonYears":1},{"id":"idea-fund-brain-metastases-programme","kind":"idea","name":"Treat brain metastases as a disease with its own trials programme","aka":[],"tldr":"A fifth of patients with solid tumours develop brain metastases and are usually excluded from trials. This would fund a programme that studies and treats them as a disease in their own right.","summary":"A funded network of brain-metastasis centres runs dedicated trials (systemic agents with CNS activity, radiosurgery sequencing, prevention in high-risk groups such as HER2-positive breast and EGFR/ALK lung cancer), builds a shared registry and tissue bank of resected metastases, and develops CNS-specific endpoints accepted by regulators. Funders and regulators would jointly discourage the routine exclusion of patients with stable brain metastases from registration trials.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Funding follows fashion, not burden): Carter & Nguyen, A comparison of cancer burden and research spending (BMC Cancer 2012)","url":"https://doi.org/10.1186/1471-2407-12-526"}],"tags":[],"related":["idea-fund-metastasis-moonshot"],"cancers":["nsclc","breast-her2-positive","melanoma","glioblastoma"],"sections":[],"technologies":["sbrt","whole-body-mri"],"targets":[],"drugs":["tucatinib","osimertinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-funding-allocation","b-brain-delivery"],"keyPapers":["paper-sun-bmc-cancer","paper-flaura-nejm-2018","paper-osimertinib-nsclc-n-engl-j-med-2017","paper-osimertinib-nsclc-n-engl-j-med-2020"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A dedicated programme raises the share of registration trials in lung, breast and melanoma that include patients with brain metastases from a minority to a majority within six years and produces at least two CNS-specific labels or guideline changes.","rationale":"Where brain metastases have been studied deliberately (tucatinib in HER2CLIMB, osimertinib CNS analyses, radiosurgery versus whole-brain trials) practice changed quickly; the constraint is that nobody funds the field systematically because it cuts across tumour-type programmes.","test":"Fund a five-centre pilot with a registry and two trials, and audit whether registration trials launched in the pilot's tumour types during the period relax their CNS exclusion criteria compared with the prior five years.","maturity":"speculative","actor":"research","cost":"large","horizonYears":6},{"id":"idea-moon-cachexia-as-treatable-disease","kind":"idea","name":"Treat cachexia as a disease: GDF-15 blockade plus anabolic and nutrition bundles","aka":[],"tldr":"The wasting that kills many cancer patients has had no effective drug. New antibodies against GDF-15 restored weight in early trials. Combine them with exercise and nutrition and test properly.","summary":"Cancer cachexia affects a large share of patients with pancreatic, lung and gastric cancer and contributes directly to death and treatment intolerance. Ponsegromab, an anti-GDF-15 antibody, increased weight and activity in a randomised phase 2 trial; ghrelin agonists (anamorelin) are approved in Japan. The proposal is a programme treating cachexia as an indication in its own right: standardised diagnosis and staging, a phase 3 of GDF-15 blockade with function and survival endpoints, and multimodal bundles combining pharmacotherapy with resistance exercise and nutritional support, embedded early in oncology care rather than at end of life.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Cachexia, toxicity and the limits of the patient): Fearon et al., Definition and classification of cancer cachexia (Lancet Oncology 2011)","url":"https://doi.org/10.1016/S1470-2045(10)70218-7"}],"tags":[],"related":[],"cancers":["pancreatic","nsclc","gastric"],"sections":[],"technologies":["exercise-oncology"],"targets":[],"drugs":[],"companies":["pfizer"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-cachexia-supportive","b-toxicity-qol"],"keyPapers":["paper-fearon-lancet-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Early multimodal cachexia treatment improves physical function and chemotherapy completion and extends overall survival in pancreatic and lung cancer by a clinically meaningful margin.","rationale":"Cachexia is mechanistically driven (GDF-15, inflammation, anorexia signalling) rather than an inevitable consequence, and the first mechanism-based drug has shown activity.","test":"Phase 3 of GDF-15 blockade plus multimodal support versus standard care in newly diagnosed metastatic pancreatic and lung cancer with cachexia; endpoints weight, function, chemotherapy dose intensity and survival.","maturity":"early-clinical","actor":"industry","cost":"large","horizonYears":5},{"id":"idea-cachexia-gdf15-prevention","kind":"idea","name":"Treat cachexia before it starts","aka":[],"tldr":"Cachexia, the muscle wasting driven partly by the hormone GDF-15, kills cancer patients and stops chemotherapy being completed, and late muscle loss is largely irreversible. Ponsegromab, an anti-GDF-15 antibody, reversed weight loss in established cachexia in 2024; the next test is a phase 3 giving it from first-line chemotherapy in pancreatic cancer to prevent wasting rather than treat it.","summary":"This idea proposes treating cachexia before it starts: wasting is a common cause of death in cancer and makes treatment impossible, and now that an effective anti-cachexia drug is in phase 3, the question is whether starting early prevents it. Ponsegromab reversed weight loss in established cachexia (2024), and GDF-15 rises early in pancreatic and lung cancer, so prevention could improve chemotherapy tolerance (Cancer cachexia pathway). The hypothesis is that anti-GDF-15 therapy from diagnosis in high-GDF-15 patients preserves muscle and increases chemotherapy completion and survival, because late muscle loss is largely irreversible. The test is a randomised phase 3 of ponsegromab from first-line chemotherapy in Pancreatic ductal adenocarcinoma; Non-small-cell lung cancer and Gastric cancer are also in scope.","asOf":"2026-09-08","links":[{"label":"Groarke et al., Ponsegromab for the treatment of cancer cachexia (NEJM 2024)","url":"https://doi.org/10.1056/NEJMoa2409515"}],"tags":["mechanism","open-question"],"related":[],"cancers":["pancreatic","nsclc","gastric"],"sections":[],"technologies":["exercise-oncology"],"targets":[],"drugs":[],"companies":[],"institutions":["fred-hutch","cold-spring-harbor"],"pathways":["cachexia-biology","jak-stat"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Anti-GDF-15 therapy started at diagnosis in high-GDF-15 patients preserves muscle mass and increases chemotherapy completion and overall survival.","rationale":"Muscle loss is largely irreversible late; GDF-15 is measurable and causal; ponsegromab is safe.","test":"Randomised phase 3 of ponsegromab vs placebo from first-line chemotherapy in metastatic pancreatic cancer with elevated GDF-15, endpoints OS and relative dose intensity.","maturity":"early-clinical"},{"id":"idea-prev-hbv-treat-all-hcc","kind":"idea","name":"Treat everyone with chronic hepatitis B to prevent liver cancer","aka":[],"tldr":"Hepatitis B causes most liver cancer worldwide, and generic tenofovir suppresses it for under 30 dollars a year. Treating everyone infected, not just those with liver damage, as WHO's 2024 guidelines allow, would cut liver cancer incidence because viral load predicts it and antivirals reduce it in cirrhotics.","summary":"Hepatitis B causes most liver cancer worldwide and cheap tablets suppress it, so this idea runs national test-and-treat-all programmes with simplified monitoring rather than restricting treatment to people with liver damage. WHO broadened treatment eligibility in its 2024 guidelines and generic tenofovir costs under 30 dollars a year; viral load predicts hepatocellular carcinoma in the REVEAL cohort and antivirals reduce it in cirrhotics, so treating everyone infected is logical and cheap. The outcome is hepatocellular carcinoma incidence in treated cohorts. The test is a stepped rollout in high-prevalence countries with registry linkage. Being tested at scale, it addresses the bottlenecks Prevention we already have is not deployed and Most of the world has almost no cancer care.","asOf":"2026-09-08","links":[{"label":"WHO hepatitis B fact sheet","url":"https://www.who.int/news-room/fact-sheets/detail/hepatitis-b"}],"tags":[],"related":[],"cancers":["hcc"],"sections":["prevention"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-prevention-adoption","b-global-access"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Treat-all reduces HCC incidence by at least half over ten years in treated adults compared with eligibility-restricted treatment.","rationale":"Viral load predicts HCC (REVEAL cohort); antivirals reduce HCC in cirrhotics; extension to all is logical and cheap.","test":"Stepped rollout in high-prevalence countries with registry linkage and cost-effectiveness modelling.","maturity":"being-tested-at-scale","actor":"policy","cost":"large","horizonYears":8},{"id":"idea-bio2-steroid-sparing-irae","kind":"idea","name":"Treat immunotherapy side-effects without wiping out the response","aka":[],"tldr":"Immune side-effects are usually treated with high-dose steroids, which may also switch off the anti-cancer response. Targeted alternatives may control the side-effect and keep the benefit.","summary":"High cumulative corticosteroid exposure for immune-related adverse events is associated with worse cancer outcomes in several cohorts, although confounding by severity is hard to exclude. Targeted alternatives (early infliximab or vedolizumab for colitis, tocilizumab for arthritis and some pneumonitis, topical or organ-directed therapy) could resolve toxicity with less systemic immunosuppression. A randomised comparison has never been done with cancer outcome as an endpoint.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (No one can predict who responds to immunotherapy): Haslam & Prasad (JAMA Network Open 2019)","url":"https://doi.org/10.1001/jamanetworkopen.2019.2535"}],"tags":[],"related":[],"cancers":["melanoma","nsclc","rcc"],"sections":[],"technologies":["checkpoint-inhibitor","monoclonal-antibody"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["irae"],"trials":[],"people":["aurelien-marabelle"],"bottlenecks":["b-immunotherapy-response","b-toxicity-qol"],"keyPapers":["paper-haslam-jama-netw-open"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Targeted first-line immunosuppression for immune-related colitis achieves faster resolution and lower cumulative steroid dose than steroids, without reducing anti-tumour efficacy.","rationale":"Targeted agents already work as steroid rescue in refractory immune colitis, so efficacy on the toxicity is established; what is untested is whether using them first preserves the anti-tumour response. The trial also improves quality of life regardless of the survival result.","test":"A randomised trial in grade 2-3 immune-related colitis comparing steroid-first with targeted-first management, with time to resolution, cumulative steroid dose and subsequent progression-free survival as endpoints.","maturity":"early-clinical","actor":"clinic","cost":"medium","horizonYears":5},{"id":"idea-nl-sleep-circadian-survivorship-rct","kind":"idea","name":"Treat insomnia in survivors and measure whether the cancer notices","aka":[],"tldr":"Insomnia therapy works well for cancer survivors and is barely offered. A trial that fixes sleep and then follows recurrence would test whether restoring the body clock changes the disease as well as the symptom.","summary":"CBT-I has strong evidence for insomnia symptoms in survivors, and disrupted rest-activity rhythms predict shorter survival in metastatic cancer, but no trial has tested whether treating sleep and circadian disruption affects recurrence or survival. Digital CBT-I and timed light therapy are scalable and cheap, making a large pragmatic trial with an oncological endpoint feasible for the first time.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Survivorship and late effects are neglected): NCI Office of Cancer Survivorship statistics","url":"https://cancercontrol.cancer.gov/ocs/statistics"}],"tags":[],"related":["idea-chronotherapy-immunotherapy"],"cancers":["breast-hr-positive","colorectal"],"sections":["nutrition-lifestyle","supportive-care"],"technologies":["sleep-circadian-interventions","chronotherapy","survivorship-care-plan","structured-exercise-survivorship"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["circadian-control"],"terms":[],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"In breast or colorectal cancer survivors with insomnia, a six-month programme of digital CBT-I plus morning bright-light exposure improves actigraphic rest-activity rhythm and reduces inflammatory markers, and over five years is associated with lower recurrence compared with sleep hygiene advice alone.","rationale":"Circadian disruption is IARC Group 2A; rest-activity dysrhythmia predicts survival; cortisol and melatonin rhythms modulate immune surveillance and cell-cycle genes in tumours. The symptom benefit alone justifies the intervention, so the trial carries no ethical cost.","test":"Pragmatic randomised trial (n about 1,200) embedded in survivorship clinics, with insomnia severity and actigraphic rhythm at 6 months as primary outcomes and recurrence-free survival at 5 years as a pre-specified secondary endpoint powered for a hazard ratio of 0.8.","maturity":"preclinical-evidence","actor":"clinic","cost":"medium","horizonYears":6},{"id":"idea-lung-never-smoker-disease-its-own-programme","kind":"idea","name":"Treat lung cancer in never-smokers as its own disease, with its own detection programme","aka":[],"tldr":"About one lung cancer in five happens to someone who never smoked, and they are outside every screening programme in the world. The genomes show it is a different disease that grows more slowly, which is exactly the kind of cancer a screening test could catch.","summary":"Sherlock-Lung sequenced 232 lung cancers in never smokers and found three subtypes defined by copy-number structure, none carrying a tobacco mutational signature. The dominant piano subtype has a low mutational burden, long telomeres and slow growth, with driver progenitor cells datable to many years before diagnosis. Hill and Swanton then showed that oncogenic EGFR and KRAS mutations are present in 18 and 53 percent of histologically normal lung tissue, and proposed that fine particulate matter promotes rather than initiates the cancer.\n\nTogether these say that never-smoker lung cancer has a long pre-clinical phase and an identifiable molecular starting point, which are the two properties that make screening work. Nobody screens for it, because eligibility everywhere is written in pack-years. UK and NHS specifics (Targeted Lung Health Check coverage and uptake, NICE positions and Cancer Drugs Fund status, molecular testing turnaround, thoracic surgery and radiotherapy capacity, audit indicators and trial access) are on the UK and NHS page for lung cancer and are not restated here.","asOf":"2026-09-25","links":[],"tags":["lung-evidence"],"related":["idea-prev-clean-air-never-smoker-endpoints","early-detection-roadmap","prevention-roadmap","lung-cancer-evidence-roadmap"],"cancers":["lung-cancer","nsclc","lung-adenocarcinoma","egfr-mutant-nsclc"],"sections":["early-detection","prevention"],"technologies":["low-dose-ct-screening","liquid-biopsy","wes-wgs"],"targets":["egfr","kras"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-early-detection","b-prevention-adoption","b-rare-cancers","b-trial-diversity"],"keyPapers":["paper-zhang-lung-cancer-never-smokers-nat-genet-2021","paper-hill-lung-adenocarcinoma-air-pollutants-nature-2023","paper-uspstf-lung-cancer-screening-jama-2021"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A detection programme aimed at never-smokers, using a risk model built from family history, ethnicity, particulate exposure, radon and lung disease rather than smoking, plus a blood-based test tuned to the slow-growing subtype, would find never-smoker lung cancer at a curable stage often enough to change mortality in that group.","rationale":"The disease is rising as a proportion of all lung cancer, disproportionately affects women and people of East Asian ancestry, and is enriched for EGFR mutations, which is to say for the tumours with the best treatment options once found. The Sherlock-Lung evolutionary timing argues that there are years of window. The air pollution work supplies both a population to enrich on and a preventive intervention with a measurable cancer endpoint.","test":"Two arms of work. First, a prospective cohort of never-smokers at elevated risk by a non-smoking risk model, with annual low-dose computed tomography and banked plasma, powered on stage distribution at diagnosis against registry controls. Second, a nested evaluation of whether ultradeep plasma sequencing detects the piano-subtype tumours before they are radiologically visible. Five to eight years to a stage-shift answer.","maturity":"preclinical-evidence","actor":"research","cost":"large","horizonYears":10},{"id":"idea-bio1-real-world-resistance-surveillance","kind":"idea","name":"Treat resistance like an infectious disease and run national surveillance","aka":[],"tldr":"Countries track how bacteria become resistant to antibiotics and publish it. Doing the same for cancer drugs would show which escape routes are becoming common and where.","summary":"Routine post-progression sequencing already happens in health systems that offer routine tumour sequencing, but the results are not aggregated. A surveillance system, modelled on antimicrobial resistance reporting, would pool de-identified mechanism data by drug, line and region, publish periodic reports, and flag emerging mechanisms early. Laboratories would submit structured results as a condition of accreditation or reimbursement.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Acquired resistance to every therapy): Soria et al., Osimertinib in untreated EGFR-mutated NSCLC (FLAURA, NEJM 2018)","url":"https://doi.org/10.1056/NEJMoa1713137"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["cgp","liquid-biopsy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["real-world-evidence","resistance"],"trials":[],"people":[],"bottlenecks":["b-resistance","b-real-world-evidence","b-data-silos"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"National surveillance detects shifts in resistance mechanism frequency (for example rising rates of a specific bypass after a new drug's uptake) at least a year earlier than the published literature.","rationale":"Antimicrobial resistance surveillance changed prescribing behaviour and guided development priorities; oncology generates the same data but discards its population-level signal.","test":"Pilot in one country aggregating results from accredited laboratories for two drug classes for 18 months, and compare detection timing of known mechanism trends with publication dates.","maturity":"speculative","actor":"policy","cost":"medium","horizonYears":4},{"id":"idea-crc-screening-uptake-and-age-extension","kind":"idea","name":"Treat screening uptake, not test sensitivity, as the thing to optimise, and settle the age extension with a trial rather than a model","aka":[],"tldr":"The only randomised trial of screening colonoscopy cut bowel cancer by 18 percent because only 42 percent of the people invited turned up. A test that is 20 percent more sensitive but is taken by the same people buys far less than an invitation that 20 percent more people accept.","summary":"NordICC randomised invitations rather than procedures, and reported a ten-year colorectal cancer risk of 0.98 against 1.20 percent, a number needed to invite of 455, and no difference in all-cause mortality; 11,843 of 28,220 invited (42.0 percent) attended. Nottingham had already shown the same pattern with a cheaper test: 40.4 percent of the screening group never completed a single kit, and 400 of 893 cancers in that arm presented in non-responders. Kaminski's data add the second half: an endoscopist's adenoma detection rate, not the offer itself, determines whether the colonoscopy that follows a positive test prevents anything.\n\nThe screening age is the other live question. The United States moved to 45 in 2021 on the strength of Siegel's birth-cohort analysis, and 20 percent of United States cases are now in people under 55. No randomised evidence exists for the extension; the decision rested on modelling, and the capacity cost falls on the same endoscopy services that are already the constraint.","asOf":"2026-09-24","links":[{"label":"Bretthauer et al.: NordICC (N Engl J Med 2022)","url":"https://europepmc.org/article/MED/36214590"},{"label":"Kaminski et al.: quality indicators and interval cancer (N Engl J Med 2010)","url":"https://europepmc.org/article/MED/20463339"},{"label":"ClinicalTrials.gov NCT00883792","url":"https://clinicaltrials.gov/study/NCT00883792"}],"tags":["colorectal-evidence"],"related":["colorectal-roadmap","early-detection-roadmap"],"cancers":["colorectal","early-onset-colorectal"],"sections":["early-detection","prevention"],"technologies":["colorectal-screening","colonoscopy","cologuard","liquid-biopsy","ai-endoscopy-detection"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["fit-test"],"trials":["nordicc"],"people":[],"bottlenecks":["b-early-detection","b-prevention-adoption","b-global-access","b-workforce"],"keyPapers":["paper-nordicc-nejm-2022","paper-hardcastle-nottingham-faecal-occult-blood-lancet-1996","paper-kaminski-adenoma-detection-rate-interval-cancer-nejm-2010","paper-imperiale-multitarget-stool-dna-screening-nejm-2014","paper-siegel-colorectal-cancer-statistics-ca-2023"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Uptake interventions with an established effect in other programmes (general practice endorsement, pre-invitation letters, text reminders, kit design, targeted outreach in the lowest-participation deciles) raise colorectal cancer screening participation by at least 10 percentage points, and deliver a larger reduction in colorectal cancer mortality per pound spent than lowering the starting age by five years.","rationale":"Programme effect is the product of test performance and participation, and participation is the term with the most headroom and the lowest marginal cost. An age extension adds the least dense part of the risk distribution to a service whose binding constraint is colonoscopy capacity.","test":"A cluster-randomised trial within a national programme comparing an uptake bundle against usual invitation, with participation at one round as the primary outcome and stage distribution and colorectal cancer mortality as long-term outcomes; alongside it, a stepped-wedge rollout of the age extension by region, so the incremental yield, the colonoscopy demand and the interval cancer rate are measured rather than modelled.","maturity":"being-tested-at-scale","actor":"policy","cost":"large","horizonYears":6},{"id":"idea-bio2-intracavitary-immunotherapy","kind":"idea","name":"Treat the body cavity, not the bloodstream, for surface spread","aka":[],"tldr":"Intracavitary immunotherapy targets cancer that coats the lining of the abdomen or chest, which drugs given by drip barely reach. Delivering it straight into the cavity gives far higher local doses.","summary":"Peritoneal and pleural surface disease has poor drug penetration from the circulation, which is why intraperitoneal chemotherapy and pressurised aerosol delivery persist despite mixed evidence. Regional immunotherapy (intraperitoneal interleukin-2, checkpoint antibodies, T-cell engagers or CAR-T cells) reaches high local concentrations, and intrapleural mesothelin CAR-T has shown feasibility. The unresolved questions are dosing, drainage-related loss and cytokine toxicity.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Cold tumours and the immunosuppressive microenvironment): Haslam & Prasad, Estimation of the percentage of US patients eligible for and responding to checkpoint inhibitors (JAMA Netw Open 2019)","url":"https://doi.org/10.1001/jamanetworkopen.2019.2535"}],"tags":[],"related":["idea-mesothelin-car-t-regional"],"cancers":["ovarian","gastric","mesothelioma"],"sections":[],"technologies":["hipec","car-t","t-cell-engager","checkpoint-inhibitor"],"targets":["mesothelin"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["peritoneal-metastasis"],"trials":[],"people":[],"bottlenecks":["b-tme-immunosuppression","b-metastasis-biology"],"keyPapers":["paper-haslam-jama-netw-open","paper-mesothelin-mesothelioma-cancer-discov-2016","paper-mesothelin-mesothelioma-clin-cancer-res-2004","paper-mesothelin-mesothelioma-j-clin-oncol-2016"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Intracavitary administration achieves at least tenfold higher local drug exposure than intravenous dosing at equal systemic exposure, and produces higher rates of cytological clearance of malignant effusion.","rationale":"Pharmacology strongly favours regional delivery for a compartmentalised disease, and cytological clearance provides a fast, objective, inexpensive endpoint. Regional cell therapy has already been shown to be safer than systemic in the pleural space.","test":"A pharmacokinetic and pharmacodynamic study comparing intracavitary with intravenous dosing of the same agent, with cytological clearance and paired compartment sampling as endpoints.","maturity":"early-clinical","actor":"clinic","cost":"medium","horizonYears":6},{"id":"idea-lung-deprivation-gradient-treated-as-a-defect-in-delivery","kind":"idea","name":"Treat the deprivation gradient in lung cancer as a defect in delivery that can be fixed and measured","aka":[],"tldr":"Poorer patients with lung cancer are less likely to be offered surgery or chemotherapy, at the same stage, in systems that are free at the point of use. That is a fixable problem in how care is delivered, not a fact about the disease.","summary":"Forrest's meta-analysis of 23 studies found that lower socioeconomic position was associated with a reduced likelihood of receiving any lung cancer treatment (odds ratio 0.79), of surgery and of chemotherapy, and that the gap was not explained by stage at presentation or by which health system the patient was in. The authors named it an intervention-generated inequality: produced by how care is organised, not by the disease.\n\nLung cancer is the cancer where this matters most, because incidence itself follows the same gradient, so the disadvantage compounds. The idea is to treat the gradient as an operational defect with named causes (distance to a thoracic surgical centre, transport, time off work, comorbidity assessment thresholds, referral behaviour, and whether the patient is offered a treatment at all) and to measure the closing of it as an outcome in its own right. UK and NHS specifics (Targeted Lung Health Check coverage and uptake, NICE positions and Cancer Drugs Fund status, molecular testing turnaround, thoracic surgery and radiotherapy capacity, audit indicators and trial access) are on the UK and NHS page for lung cancer and are not restated here.","asOf":"2026-09-25","links":[],"tags":["lung-evidence"],"related":["idea-prev-mobile-lung-screening-deprived-areas","global-access-roadmap","lung-cancer-evidence-roadmap"],"cancers":["lung-cancer","nsclc","sclc"],"sections":["early-detection","surgery"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-global-access","b-care-fragmentation","b-workforce","b-trial-diversity","b-real-world-evidence"],"keyPapers":["paper-forrest-socioeconomic-inequalities-lung-cancer-treatment-plos-med-2013","paper-uspstf-lung-cancer-screening-jama-2021","paper-aldrich-uspstf-screening-african-american-smokers-jama-oncol-2019"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A bundle aimed at the named delivery defects (screening and diagnostics placed in deprived areas, transport and appointment support, prehabilitation to raise fitness before surgical assessment, and mandatory recording of treatments offered as well as delivered) narrows the treatment-receipt gap between deprivation quintiles at matched stage, and narrows the stage-adjusted survival gap with it.","rationale":"The effect is documented, sizeable, stage-independent and present across health systems, which means it is not a funding problem alone. Each proposed component has independent evidence: mobile screening units raise uptake in deprived areas, prehabilitation raises measured fitness before thoracic surgery, and recording what was offered rather than only what was given makes the decision point visible where it is currently invisible.","test":"A stepped-wedge implementation trial across cancer networks, with treatment receipt at matched stage by deprivation quintile as the primary outcome and stage-adjusted one-year survival as the secondary. Requires linked registry and treatment data, and an agreed measure of treatment offered as distinct from treatment received. Three to five years.","maturity":"early-clinical","actor":"policy","cost":"medium","horizonYears":5},{"id":"idea-bio2-lymph-node-immune-priming","kind":"idea","name":"Treat the draining lymph node before removing it","aka":[],"tldr":"The first lymph node cancer reaches is also where the immune system learns to fight it. Injecting immunotherapy into that node before surgery, instead of removing it blindly, may work better.","summary":"Tumour-draining lymph nodes hold the stem-like precursor T cells that checkpoint blockade depends on, so removing or irradiating them may remove the substrate of response. Peritumoural or intranodal injection achieves high nodal exposure at a small fraction of the systemic dose, and small trials of peritumoural nivolumab in oral cancer and intratumoural ipilimumab in melanoma showed nodal immune activation.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Metastasis is understood least and studied last): Dillekås et al., Are 90% of deaths from cancer caused by metastases? (Cancer Medicine 2019)","url":"https://doi.org/10.1002/cam4.2474"}],"tags":[],"related":[],"cancers":["head-and-neck","melanoma"],"sections":[],"technologies":["checkpoint-inhibitor","sentinel-node"],"targets":[],"drugs":["nivolumab","ipilimumab"],"companies":[],"institutions":[],"pathways":[],"terms":["major-pathological-response","irae"],"trials":["checkmate-067","checkmate-238","checkmate-915","nadina","nivopostop"],"people":["christian-blank","john-haanen"],"bottlenecks":["b-metastasis-biology","b-tme-immunosuppression","b-toxicity-qol"],"keyPapers":["paper-dillekas-cancer-med","paper-hodi-ipilimumab-melanoma-nejm-2010","paper-nivolumab-melanoma-n-engl-j-med-2015","paper-keynote-006-pembrolizumab-ipilimumab-melanoma-nejm-2015"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Low-dose peritumoural or intranodal checkpoint blockade before surgery produces pathological response at least as good as systemic dosing, with fewer immune-related adverse events, in early oral cavity cancer and melanoma.","rationale":"Antigen presentation and T-cell priming happen in the node, not the tumour, while the dose-limiting toxicity of checkpoint blockade is systemic. Concentrating the drug where priming occurs is a pharmacology argument rather than a new mechanism.","test":"Randomised neoadjuvant window trial comparing low-dose peritumoural against standard intravenous checkpoint blockade, with major pathological response and nodal immune profiling as co-primary endpoints.","maturity":"early-clinical","actor":"clinic","cost":"medium","horizonYears":6},{"id":"idea-cost-trial-enrolment-cost-lever","kind":"idea","name":"Treat trial enrolment as a cost lever: the sponsor pays for the drug","aka":[],"tldr":"In a clinical trial the experimental drug is free to the patient and the payer, and since 2022 Medicaid must cover routine trial costs like Medicare and private plans do; pointing more patients to trials lowers bills as well as advancing science.","summary":"Fewer than one in ten adults with cancer join a trial, and cost concerns about routine care coverage are a documented barrier. The Clinical Treatment Act (effective January 2022) requires state Medicaid programmes to cover routine costs in qualifying trials, joining Medicare (since 2000) and Affordable Care Act plans. With the sponsor supplying the drug, a trial arm is often the cheapest way to receive a new therapy. Systematic trial matching at diagnosis, and payer navigators who present trials alongside coverage options, would turn a research goal into a cost tool.","asOf":"2026-09-10","links":[{"label":"Medicaid.gov: coverage of routine patient costs in clinical trials (Clinical Treatment Act)","url":"https://www.medicaid.gov/federal-policy-guidance/downloads/cib122921.pdf"},{"label":"Medicare.gov: Clinical research studies","url":"https://www.medicare.gov/coverage/clinical-research-studies"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["ai-trial-matching"],"targets":[],"drugs":[],"companies":[],"institutions":["nci"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-enrolment","b-drug-pricing","b-trial-diversity"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Routine trial matching with coverage counselling will double enrolment in participating practices and lower payer drug spend per enrolled patient by the cost of the investigational agent.","rationale":"The coverage law is now uniform across public payers; the remaining gap is awareness and matching effort.","test":"Practice-level pilot with enrolment rates, patient out-of-pocket costs and payer spend for enrolled versus matched non-enrolled patients.","maturity":"being-tested-at-scale","actor":"policy","cost":"small","horizonYears":2},{"id":"idea-bio2-cachexia-pathway-code","kind":"idea","name":"Treat wasting like sepsis: a trigger, a bundle, an audit","aka":[],"tldr":"Hospitals have fast, standard responses to sepsis and heart attacks. Cancer wasting has no such pathway, so it is noticed late and treated inconsistently.","summary":"Cachexia care is fragmented across oncology, dietetics, physiotherapy and palliative care, with no trigger threshold and no bundle. A defined pathway is a service intervention that requires no new drug: automatic trigger on weight loss or low muscle mass, same-week multidisciplinary assessment, a standard bundle of nutrition, resistance exercise, symptom control and medication review, and audited outcomes.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Cachexia, toxicity and the limits of the patient): Fearon et al., Definition and classification of cancer cachexia (Lancet Oncology 2011)","url":"https://doi.org/10.1016/S1470-2045(10)70218-7"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["exercise-oncology","geriatric-assessment"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["nathan-cherny"],"bottlenecks":["b-cachexia-supportive","b-care-fragmentation","b-palliative"],"keyPapers":["paper-fearon-lancet-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A triggered cachexia bundle increases the proportion of at-risk patients receiving nutritional and exercise intervention from a minority to over 70%, and improves treatment completion and quality of life.","rationale":"Bundled care with automatic triggers transformed sepsis, stroke and hip fracture outcomes by reducing variation rather than adding technology. Cachexia has the same profile: known components, poor delivery.","test":"Stepped-wedge implementation across several centres with process measures and patient-reported outcomes, plus a cost analysis of avoided admissions.","maturity":"speculative","actor":"clinic","cost":"small","horizonYears":4},{"id":"idea-tr1-ehr-point-of-care-trial-alert","kind":"idea","name":"Trial matching inside the electronic record at the moment a treatment is chosen","aka":[],"tldr":"When an oncologist opens the order screen to prescribe a new line of treatment, the record would show the trials this patient may fit, with the nearest open site and a one-click referral.","summary":"Eligibility criteria are encoded in a structured, computable form (mCODE/FHIR profiles for stage, biomarkers, prior lines, performance status) and matched against the patient's record inside the EHR order-set workflow, not in a separate portal. Alerts fire only at decision points (new line of therapy, progression documented) to avoid fatigue. Several AI matching tools exist; the missing piece is embedding at the point of decision with a referral action.","asOf":"2026-09-08","links":[{"label":"mCODE (minimal Common Oncology Data Elements)","url":"https://mcodeinitiative.org/"},{"label":"HL7 FHIR","url":"https://hl7.org/fhir/"}],"tags":[],"related":["clinicaltrials-gov"],"cancers":[],"sections":[],"technologies":["ai-trial-matching"],"targets":[],"drugs":[],"companies":["tempus","cancer-commons"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-enrolment","b-data-silos"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Point-of-decision matching will double the proportion of eligible patients who are offered a trial in participating practices, measured by chart review, compared with practices using the same matching tool in a stand-alone portal.","rationale":"Most patients are never told about a trial; the failure is at the moment of prescribing, when the physician's attention is on the standard option. Decision-support that appears at that moment changes prescribing behaviour in other fields (antibiotic stewardship, anticoagulation).","test":"Cluster-randomised trial across 20 community oncology practices sharing one EHR vendor: embedded alert versus portal-only, primary outcome trial offer rate documented in notes, secondary enrolment rate.","maturity":"early-clinical","actor":"engineering","cost":"medium","horizonYears":3},{"id":"idea-tr1-rare-cancer-trial-in-a-box","kind":"idea","name":"Trial-in-a-box: a preconfigured protocol kit any hospital can open for a rare cancer","aka":[],"tldr":"For rare cancers, the patient is often at a hospital that has no trial. A ready-made kit with the protocol, consent forms, database and shipping already set up would let that hospital enrol them within days.","summary":"A cooperative group or rare-cancer consortium maintains modular, pre-approved protocol packages for rare histologies: template protocol with pre-negotiated ethics approval under a central IRB, eConsent, cloud EDC, sample-shipping kits and a remote investigator-of-record model where local clinicians act as sub-investigators. Combined with just-in-time activation, the kit lets any accredited hospital enrol its one patient.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Trials enrol too few, too slowly): Unger et al., Systematic review of barriers to cancer trial participation (JNCI 2019)","url":"https://doi.org/10.1093/jnci/djy221"}],"tags":[],"related":[],"cancers":["sarcoma","neuroendocrine","mesothelioma","cholangiocarcinoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["curie-nki-eortc"],"institutions":[],"pathways":[],"terms":["basket-umbrella-platform"],"trials":[],"people":[],"bottlenecks":["b-trial-enrolment","b-rare-cancers"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Rare-cancer trials using a trial-in-a-box model will enrol from at least three times as many sites and reach accrual targets faster than conventional multicentre rare-cancer trials.","rationale":"Rare-cancer trials fail on accrual because patients are scattered; every patient not enrolled is a large fraction of the target. Paediatric oncology achieves high enrolment through standardised cooperative-group infrastructure that adult rare-cancer trials lack.","test":"Deploy a kit for one rare adult sarcoma or neuroendocrine subtype across a national network and compare enrolment per eligible incident case with a historical trial in the same subtype.","maturity":"speculative","actor":"research","cost":"medium","horizonYears":3},{"id":"idea-acc-methadone-and-alternatives-where-morphine-fails","kind":"idea","name":"Trials of low-cost opioid alternatives where morphine supply is unreliable","aka":[],"tldr":"When morphine is unavailable, patients get nothing. Some cheap alternatives, such as methadone or tramadol, may work for cancer pain but have not been properly tested in these settings.","summary":"Morphine stock-outs are common in LMICs, leaving patients without analgesia. Methadone is inexpensive, long-acting, and effective for cancer pain but needs careful titration; tramadol is widely available but weaker and not internationally controlled, which affects supply differently. Pragmatic trials of protocolised methadone or tramadol-based regimens delivered by nurses in settings with unreliable morphine would establish safe fallback options and could inform essential medicines lists.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Pain relief and palliative care are unavailable to most): WHO fact sheet, Palliative care","url":"https://www.who.int/news-room/fact-sheets/detail/palliative-care"}],"tags":[],"related":["idea-acc-chemo-stockout-early-warning"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-palliative","b-global-access"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A protocolised methadone regimen delivered by trained nurses will achieve pain control non-inferior to oral morphine in patients with moderate to severe cancer pain, with acceptable safety.","rationale":"Methadone is already used for cancer pain by specialists in high-income countries and is on the WHO essential medicines list; the question is safe delivery by non-specialists.","test":"A randomised non-inferiority trial in three LMIC centres comparing methadone protocol with morphine on pain scores at two weeks, with sedation and QT monitoring as safety endpoints.","maturity":"speculative","actor":"research","cost":"medium","horizonYears":4},{"id":"idea-acc-cognitive-rehabilitation-after-chemotherapy","kind":"idea","name":"Trials of structured cognitive rehabilitation for cancer-related cognitive impairment","aka":[],"tldr":"A substantial minority of survivors report foggy thinking and memory problems for years after chemotherapy, limiting work and daily life, and no funded service exists for it. Small trials of computerised cognitive training, strategy training and exercise show benefit; a definitive multi-arm trial with a functional endpoint would establish or refute a treatable condition.","summary":"Cancer-related cognitive impairment affects a substantial minority of survivors and limits work and daily function. Small trials of computerised cognitive training, cognitive-behavioural strategy training, and exercise show benefit on self-reported and some objective measures, but there is no standard of care and no funded service. A definitive multi-arm trial comparing the leading approaches, with a functional primary endpoint, would establish or refute a treatable condition.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Survivorship and late effects are neglected): NCI Office of Cancer Survivorship statistics","url":"https://cancercontrol.cancer.gov/ocs/statistics"}],"tags":[],"related":["idea-exercise-as-adjuvant"],"cancers":[],"sections":["rejuvenation"],"technologies":["exercise-oncology"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"At least one structured cognitive rehabilitation approach will produce a clinically meaningful improvement in perceived cognitive function and work ability at six months compared with attention control.","rationale":"Rehabilitation improves outcomes after stroke and brain injury with similar mechanisms of compensation and neuroplasticity; survivors are motivated and the intervention is low risk.","test":"A four-arm randomised trial (computerised training, strategy training, exercise, attention control) in 800 survivors with a validated perceived-cognition instrument as primary endpoint.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":4},{"id":"idea-tnbc-brain-metastasis-trials","kind":"idea","name":"Trials that include, and report, brain metastases in triple-negative breast cancer","aka":[],"tldr":"Nearly half of women with metastatic triple-negative breast cancer develop brain metastases and survive under five months after the diagnosis, yet the trials that set the standard mostly exclude active brain disease. Requiring a brain metastasis cohort in every phase 3, with intracranial response as an endpoint, would answer whether the new drugs reach the brain.","summary":"Lin's Dana-Farber series found central nervous system metastases in 14 percent at first metastatic diagnosis and 46 percent before death, with a median survival of 4.9 months after the brain diagnosis and only 3 of 53 patients with controlled systemic disease, arguing that the problem is a lack of effective therapy rather than a sanctuary effect. The immunotherapy and antibody-drug conjugate trials generally admitted only treated, stable brain metastases and did not report intracranial endpoints; trastuzumab deruxtecan has shown intracranial activity in HER2-positive disease, and case series suggest sacituzumab govitecan crosses into brain lesions, but there is no randomised evidence in triple-negative disease. The bottleneck record for brain delivery describes the general problem.","asOf":"2026-09-24","links":[{"label":"Lin et al.: sites of distant recurrence in metastatic triple-negative breast cancer, high incidence of central nervous system metastases (Cancer 2008)","url":"https://europepmc.org/article/MED/18833576"}],"tags":["tnbc-evidence"],"related":[],"cancers":["tnbc"],"sections":[],"technologies":["adc"],"targets":[],"drugs":["sacituzumab-govitecan","datopotamab-deruxtecan","trastuzumab-deruxtecan"],"companies":[],"institutions":["dana-farber"],"pathways":[],"terms":["brain-metastases"],"trials":["tropion-breast05","izabright-breast01","ascent-04"],"people":["nancy-lin"],"bottlenecks":["b-brain-delivery","b-metastasis-biology","b-trial-design"],"keyPapers":["paper-lin-tnbc-cns-metastases-dfci-cancer-2008","paper-tropion-breast02-ann-oncol-2026"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Including a pre-specified cohort of patients with active or untreated brain metastases in first-line antibody-drug conjugate trials will show an intracranial objective response rate above 30 percent for at least one conjugate and will identify a group in whom systemic therapy can defer or replace whole-brain radiotherapy.","rationale":"The population is large, the outcome is poor, the drugs plausibly penetrate, and exclusion leaves clinicians extrapolating; a cohort adds cost but no new molecule.","test":"A brain metastasis cohort with intracranial response by RANO-BM criteria and time to whole-brain radiotherapy in TROPION-Breast05 and IZABRIGHT-Breast01 or their successors; a dedicated randomised phase 2 of TROP2 conjugate versus physician's choice in active brain metastases; mandatory reporting of central nervous system recurrence in adjuvant trials.","maturity":"early-clinical","actor":"industry","cost":"medium","horizonYears":4},{"id":"idea-trop2-pet-selection","kind":"idea","name":"TROP2 PET to choose and sequence TROP2 ADCs","aka":[],"tldr":"Use a whole-body TROP2 scan instead of a single tissue stain to decide which patients get a TROP2 ADC, which one, and when to switch.","summary":"The proposal is to use a whole-body TROP2 PET scan, rather than a single tissue stain, to decide which patients receive a TROP2 ADC, which agent they get and when to switch. Baseline uptake and heterogeneity would predict benefit, and a fall in uptake at progression would signal antigen loss that should prompt a move to a non-TROP2 ADC rather than a second TROP2 agent. IHC on archival tissue failed to predict sacituzumab govitecan benefit, whereas PSMA PET already plays this role for Pluvicto and 89Zr-antibody and 68Ga-nanobody tracers image human tumours. The test is an imaging sub-study inside a first-line TNBC ADC trial, then a randomised PET-guided versus standard sequencing trial. At early-clinical maturity, it bears on the bottleneck Biomarkers are not validated or standardised.","asOf":"2026-09-04","links":[{"label":"ASCENT: sacituzumab govitecan doubles survival in heavily pretreated metastatic triple-negative breast cancer (New England Journal of Medicine 2021)","url":"https://doi.org/10.1056/NEJMoa2028485"}],"tags":[],"related":["trop2-pet-to-adc","psma-pet-to-rlt"],"cancers":["tnbc","nsclc"],"sections":[],"technologies":["trop2-pet","adc","immuno-pet"],"targets":["trop2"],"drugs":["sacituzumab-govitecan","datopotamab-deruxtecan","sacituzumab-tirumotecan"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["ascent","ascent-03","ascent-04","tropion-breast02","tropion-lung01"],"people":[],"bottlenecks":[],"keyPapers":["paper-ascent-nejm-2021","paper-sacituzumab-govitecan-tnbc-n-engl-j-med-2019","paper-sacituzumab-govitecan-tnbc-j-clin-oncol-2017"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Baseline TROP2 PET uptake (SUV, heterogeneity index) predicts PFS on TROP2 ADCs better than IHC, and a fall in uptake at progression indicates antigen-loss resistance that should prompt a switch to a non-TROP2 ADC rather than a second TROP2 agent.","rationale":"PSMA PET does exactly this for Pluvicto. TROP2 is internalising and abundant; 89Zr-antibody and 68Ga-nanobody tracers already image human tumours.","test":"Prospective imaging sub-study in a first-line TNBC ADC trial (e.g., a TROPION-Breast05 or sac-TMT cohort) correlating baseline and on-treatment TROP2 PET with response and PFS; then a randomised PET-guided vs standard sequencing trial.","maturity":"early-clinical"},{"id":"idea-bio1-tumour-on-chip-penetration","kind":"idea","name":"Tumour-on-a-chip with blood flow to test whether big drugs actually get in","aka":[],"tldr":"Large drugs such as antibody-drug conjugates must cross vessel walls and travel through dense tissue. A chip with flowing channels and human tissue can measure how far they get.","summary":"Microphysiological systems with perfusable endothelial channels, stromal fibroblasts and tumour spheroids reproduce interstitial pressure, matrix density and convective transport, the variables that determine ADC, radioligand and nanoparticle penetration. Standard flat cultures and mouse models cannot measure human tissue penetration directly, and penetration is a leading cause of clinical underperformance for large modalities.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Lab models that fail to predict what happens in patients): Wong, Siah & Lo, Estimation of clinical trial success rates (Biostatistics 2019)","url":"https://doi.org/10.1093/biostatistics/kxx069"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["adc","organoids","radioligand-therapy"],"targets":[],"drugs":["trastuzumab-deruxtecan","sacituzumab-govitecan"],"companies":[],"institutions":[],"pathways":[],"terms":["payload","bystander-effect"],"trials":[],"people":[],"bottlenecks":["b-preclinical-models"],"keyPapers":["paper-wong-biostatistics"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Chip-measured penetration depth and payload delivery rank a set of ADCs in the same order as their observed clinical activity in matched indications.","rationale":"Payload delivered per gram of tumour is a mechanistic determinant of ADC efficacy; the binding-site barrier and stromal exclusion are well described but rarely measured before clinical trials.","test":"Benchmark five clinically characterised ADCs with divergent outcomes on a standardised chip and correlate penetration metrics with reported response rates.","maturity":"preclinical-evidence","actor":"engineering","cost":"small","horizonYears":3},{"id":"idea-bio1-pp2a-activators","kind":"idea","name":"Turn a brake back on: drugs that reactivate the PP2A phosphatase","aka":[],"tldr":"Cells have an enzyme, PP2A, that removes the growth signals cancer relies on. Cancers switch it off. Drugs that switch it back on are an unusual and largely untried approach.","summary":"PP2A is a tumour suppressor phosphatase that cancers inactivate through SET, CIP2A or subunit mutations. Small-molecule activators of PP2A (SMAPs) and the related class of phosphatase-directed compounds destabilise MYC and other oncoproteins by promoting their dephosphorylation and degradation. Activating an enzyme is harder than inhibiting one, which is why the class is underdeveloped.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The undruggable drivers): Dang et al., Drugging the 'undruggable' cancer targets (Nature Reviews Cancer 2017)","url":"https://doi.org/10.1038/nrc.2017.36"}],"tags":[],"related":[],"cancers":["nsclc"],"sections":[],"technologies":[],"targets":["kras"],"drugs":[],"companies":[],"institutions":[],"pathways":["ras-mapk"],"terms":[],"trials":[],"people":[],"bottlenecks":["b-undruggable-targets"],"keyPapers":["paper-dang-nat-rev-cancer","paper-kras-nsclc-n-engl-j-med-2021","paper-kras-nsclc-cancer-discov-2018","paper-kras-nsclc-j-clin-oncol-2005"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"PP2A activation lowers MYC protein levels in tumours in vivo and synergises with MEK or CDK4/6 inhibition to produce durable regressions in models where either agent alone fails.","rationale":"Phosphatase activation attacks the stability of undruggable oncoproteins indirectly; MYC's short half-life makes it especially sensitive to dephosphorylation at the residue that protects it from degradation.","test":"In vivo pharmacodynamics of a tool SMAP in KRAS-driven lung models, with MYC protein and phospho-site readouts, and a combination matrix with MEK inhibition.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":7},{"id":"idea-bio1-cin-vulnerability-kif18a","kind":"idea","name":"Turn chromosomal chaos into a weakness with KIF18A inhibitors","aka":[],"tldr":"Chromosomally unstable, often whole-genome-doubled tumours survive constant chromosome mistakes by depending on the motor protein KIF18A, which diploid cells do not need. Blocking it kills unstable cancer cells while sparing normal ones; inhibitors are in early trials in ovarian and other cancers.","summary":"Chromosomally unstable, often whole-genome-doubled tumours depend on the kinesin KIF18A for mitotic fidelity, whereas diploid cells do not. KIF18A inhibitors are in early trials in ovarian and other CIN-high cancers. The proposal is to use CIN and whole-genome doubling, measured from routine sequencing, as the selection biomarker and to test KIF18A inhibition specifically after platinum resistance, when instability is highest.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Tumour heterogeneity and clonal evolution): Gerlinger et al., Intratumor heterogeneity and branched evolution (NEJM 2012)","url":"https://doi.org/10.1056/NEJMoa1113205"}],"tags":[],"related":[],"cancers":["ovarian","tnbc"],"sections":[],"technologies":["synthetic-lethality-approaches","crispr-screens"],"targets":[],"drugs":[],"companies":["amgen"],"institutions":[],"pathways":[],"terms":["synthetic-lethality"],"trials":[],"people":[],"bottlenecks":["b-tumor-heterogeneity","b-undruggable-targets"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"KIF18A inhibition produces objective responses predominantly in tumours with high CIN scores and whole-genome doubling, and CIN score outperforms histology as the selection criterion.","rationale":"Synthetic lethality with CIN was identified in CRISPR screens; heterogeneity-generating instability is thereby converted from the tumour's advantage into a targetable dependency.","test":"Biomarker-enriched phase 2 in platinum-resistant high-grade serous ovarian and TNBC with pre-specified CIN-high and CIN-low strata; compare response rates.","maturity":"early-clinical","actor":"industry","cost":"medium","horizonYears":3},{"id":"idea-bio1-mutagenesis-blockade-rev1","kind":"idea","name":"Turn off the error-prone repair that manufactures resistance mutations","aka":[],"tldr":"Under treatment stress, cancer cells switch on sloppy DNA copying that generates the mutations they need to survive. Blocking that machinery could stop resistance being invented.","summary":"Stress-induced mutagenesis through translesion synthesis polymerases (REV1, POLZ) accelerates the emergence of resistance in bacteria and in cancer cells. REV1 inhibitors have been described and shown to reduce chemotherapy-induced mutagenesis and delay resistance in models. Given as an adjunct rather than a cytotoxic, the aim is to lower the mutation supply rate rather than to kill cells.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Acquired resistance to every therapy): Soria et al., Osimertinib in untreated EGFR-mutated NSCLC (FLAURA, NEJM 2018)","url":"https://doi.org/10.1056/NEJMoa1713137"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["ddr"],"terms":["mutational-signature","resistance"],"trials":[],"people":[],"bottlenecks":["b-resistance"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Co-administration of a translesion synthesis inhibitor with chemotherapy or targeted therapy reduces the acquisition of new resistance mutations and prolongs time to progression in vivo.","rationale":"Resistance requires variation; reducing the rate at which variation is generated is a validated strategy against bacterial resistance and has direct molecular counterparts in cancer.","test":"In vivo resistance-emergence studies with and without a REV1 inhibitor, using barcoded models to distinguish selection of pre-existing clones from newly generated mutations.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":7},{"id":"idea-bio2-in-situ-vaccination-solid","kind":"idea","name":"Turn one tumour into a vaccine to treat all the others","aka":[],"tldr":"Injecting immune-activating agents into a single tumour, plus a small dose of radiation, can teach the immune system to attack tumours elsewhere in the body.","summary":"The in situ vaccine combination of Flt3L to recruit dendritic cells, low-dose radiotherapy to release antigen, and a TLR3 agonist to mature the dendritic cells produced systemic regressions in indolent lymphoma in a phase 1/2 at Mount Sinai. The approach needs no antigen identification and no manufacturing, and has never been properly tested in solid tumours where antigen release by radiotherapy is well characterised.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Cold tumours and the immunosuppressive microenvironment): Haslam & Prasad, Estimation of the percentage of US patients eligible for and responding to checkpoint inhibitors (JAMA Netw Open 2019)","url":"https://doi.org/10.1001/jamanetworkopen.2019.2535"}],"tags":[],"related":[],"cancers":["dlbcl","head-and-neck","sarcoma"],"sections":[],"technologies":["sting-agonist","sbrt","checkpoint-inhibitor"],"targets":[],"drugs":[],"companies":[],"institutions":["mount-sinai"],"pathways":[],"terms":["abscopal-effect","immunogenic-cell-death","cold-vs-hot"],"trials":[],"people":[],"bottlenecks":["b-tme-immunosuppression","b-immunotherapy-response"],"keyPapers":["paper-haslam-jama-netw-open"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Intratumoural Flt3L plus low-dose radiotherapy plus a TLR3 agonist induces abscopal responses in at least 15% of patients with checkpoint-refractory solid tumours, with expansion of shared T-cell clones between injected and non-injected lesions.","rationale":"Antigen supply and dendritic cell availability are the two rate-limiting steps for priming in cold tumours, and this regimen supplies both locally at low systemic cost. Clonal sharing between lesions is a hard mechanistic endpoint that does not depend on tumour shrinkage.","test":"A multi-cohort phase 2 in checkpoint-refractory solid tumours with paired injected and distant lesion biopsies and T-cell receptor sequencing as the primary mechanistic endpoint.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":6},{"id":"idea-reg-orbis-work-sharing","kind":"idea","name":"Turn Project Orbis into a work-sharing review with one shared assessment report","aka":[],"tldr":"Regulators in several countries already look at the same cancer drug dossier at the same time. Let them split the work and write one report instead of six.","summary":"Project Orbis (FDA Oncology Center of Excellence, with Australia, Canada, UK, Switzerland, Singapore, Brazil, Israel) coordinates concurrent review but each agency still writes its own full assessment. The proposal is formal work-sharing: one agency leads clinical, another CMC, another statistics, producing a single shared assessment report that each partner adopts with a short national addendum. The Access Consortium already work-shares among smaller agencies; extending the model to Orbis would remove most duplicated review effort.","asOf":"2026-09-08","links":[{"label":"FDA Project Orbis","url":"https://www.fda.gov/about-fda/oncology-center-excellence/project-orbis"}],"tags":[],"related":["fda-approvals"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-regulatory-fragmentation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Work-shared Orbis reviews reduce the median gap between first and last partner approval from months to under 30 days without an increase in post-approval label changes or safety withdrawals within three years.","rationale":"Assessment reports for the same dossier reach the same conclusions the vast majority of the time; the cost is in the writing, not the disagreement. The EU centralised procedure has run a rapporteur/co-rapporteur split for decades and Access Consortium work-sharing has cut review time without measurable safety cost.","test":"Pilot 20 consecutive Orbis oncology submissions with a work-shared single report and compare time-to-last-approval and post-marketing label changes with the previous 20 conventional Orbis reviews.","maturity":"being-tested-at-scale","actor":"regulator","cost":"small","horizonYears":2},{"id":"idea-bio2-spatial-signature-cdx","kind":"idea","name":"Turn the map of immune cells inside a tumour into a standardised test","aka":[],"tldr":"Whether immune cells are next to cancer cells matters more than how many there are. Turning that spatial picture into a reliable, standardised test would predict response better.","summary":"Spatial features such as the distance from cytotoxic T cells to tumour cells, the presence of immune-excluded phenotypes and B-cell aggregates outperform PD-L1 and tumour mutational burden in retrospective series. No spatial assay has been standardised as a companion diagnostic, and platform variability, staining variability and analytical drift are unaddressed. Reference tissue standards and a locked analysis pipeline are the prerequisites.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (No one can predict who responds to immunotherapy): Haslam & Prasad (JAMA Network Open 2019)","url":"https://doi.org/10.1001/jamanetworkopen.2019.2535"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["single-cell-spatial","digital-pathology-ai","companion-diagnostic","pathology-foundation-model"],"targets":[],"drugs":[],"companies":["10x-genomics","paige","bostongene","lunit"],"institutions":[],"pathways":[],"terms":["tps","cps","tils","cold-vs-hot"],"trials":[],"people":[],"bottlenecks":["b-immunotherapy-response","b-biomarker-validation","b-ai-validation"],"keyPapers":["paper-haslam-jama-netw-open"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A locked spatial signature with defined reference materials predicts checkpoint benefit with a higher c-statistic than PD-L1 immunohistochemistry across at least three tumour types, and is reproducible between laboratories to within a defined tolerance.","rationale":"PD-L1 scoring itself became clinically usable only after harmonisation efforts and defined scoring rules, despite its known weakness. Spatial biology has better biological content and is following the same path, but has not yet done the metrology.","test":"A multi-laboratory ring study on shared reference slides to quantify reproducibility, then retrospective validation of a locked signature in banked trial tissue with pre-registered thresholds.","maturity":"early-clinical","actor":"industry","cost":"medium","horizonYears":5},{"id":"idea-reg-two-day-cart-rapid-release","kind":"idea","name":"Two-day CAR-T manufacture paired with rapid release tests that regulators accept","aka":[],"tldr":"CAR-T can now be made in a day or two, but the safety tests to release it still take two weeks. Faster tests would let patients be treated within days.","summary":"Non-expanded or minimally expanded CAR-T processes (Novartis T-Charge and rapcabtagene autoleucel, several academic protocols) produce a product in 24-48 hours, but release still waits for compendial 14-day sterility, mycoplasma and vector copy number assays. The proposal is a regulatory pathway for rapid release: validated rapid microbial methods (PCR- or growth-based, 24-72 hours), qPCR mycoplasma, flow-based potency surrogates, and 'release-then-confirm' with infusion permitted after rapid tests and compendial tests completed in parallel, as is already accepted for some cord blood and radiopharmaceutical products.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Manufacturing cost and time for living and radioactive medicines): Hernandez, Prasad & Gellad, Total costs of chimeric antigen receptor T-cell immunotherapy (JAMA Oncology 2018)","url":"https://doi.org/10.1001/jamaoncol.2018.0977"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["car-t"],"targets":[],"drugs":[],"companies":["novartis"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-manufacturing-cell-therapy"],"keyPapers":["paper-hernandez-jama-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Rapid release cuts vein-to-vein time for fast-manufactured CAR-T to under seven days and reduces the proportion of enrolled patients who die or progress before infusion by half, with no increase in infusion-related infections.","rationale":"Ten to twenty percent of patients referred for CAR-T never receive it, largely because of progression during the wait. Short manufacture also yields less differentiated, more persistent T cells. Rapid sterility methods are validated in blood banking and radiopharmacy where product shelf life forces the issue.","test":"Sponsor a regulator-endorsed validation study of rapid microbial methods against compendial methods on 500 CAR-T batches, then a prospective cohort using release-then-confirm with 30-day infection surveillance.","maturity":"early-clinical","actor":"regulator","cost":"medium","horizonYears":3},{"id":"idea-moon-plain-language-consent","kind":"idea","name":"Two-page plain-language consent with teach-back for every cancer trial and treatment","aka":[],"tldr":"Replace 30-page consent forms with a short plain summary the patient explains back in their own words before signing, so consent means understanding.","summary":"Trial consent documents run to tens of pages at university reading level; comprehension studies show many participants cannot state the purpose of the study or that treatment is experimental. The proposal is a regulatory requirement that every consent process include a two-page plain-language summary (reading age 12, translated, with pictograms for risk) followed by a documented teach-back, with the long form as an appendix. The EU Clinical Trials Regulation already requires lay summaries of results; this extends the principle upstream.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Patients lack understanding, navigation and agency): Basch et al., Overall survival results of a trial assessing patient-reported outcomes for symptom monitoring during routine cancer treatment (JAMA 2017)","url":"https://doi.org/10.1001/jama.2017.7156"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-patient-voice","b-trial-enrolment"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Short-form consent with teach-back raises objective comprehension scores (e.g., QuIC) by 20 points or more without reducing enrolment, and reduces later withdrawal for misunderstanding.","rationale":"Comprehension is a product of format, not patient intelligence. Teach-back is standard in patient safety, and shorter consent has performed as well or better than long forms in randomised comparisons of consent formats.","test":"Randomised comparison of standard versus short-form-plus-teach-back consent across ten trials; primary endpoint comprehension score at 24 hours, secondary endpoints enrolment, withdrawal and time to consent.","maturity":"early-clinical","actor":"regulator","cost":"small","horizonYears":2},{"id":"idea-bio1-dual-antigen-adc-escape","kind":"idea","name":"Two-target antibody drugs to close the antigen escape route","aka":[],"tldr":"If a drug relies on one marker, the tumour can survive by dropping it. A drug that recognises two markers at once makes that escape harder.","summary":"Bispecific ADCs binding two tumour antigens can retain binding and internalisation when one antigen is lost, and may improve selectivity where either antigen alone is present on normal tissue. Several bispecific ADCs are in clinical development. The proposal is to test the antigen-escape hypothesis explicitly by comparing a bispecific ADC with its monospecific parent and measuring antigen status at progression.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Acquired resistance to every therapy): Soria et al., Osimertinib in untreated EGFR-mutated NSCLC (FLAURA, NEJM 2018)","url":"https://doi.org/10.1056/NEJMoa1713137"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["bispecific-adc","adc"],"targets":[],"drugs":["izalontamab-brengitecan"],"companies":["systimmune","bms"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-resistance","b-tumor-heterogeneity"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Patients treated with a bispecific ADC show a lower rate of antigen-loss-mediated resistance at progression than those treated with the matched monospecific ADC, with comparable toxicity.","rationale":"Dual-antigen targeting reduced escape in CAR-T experience with CD19 and CD22; the mechanism of escape is the same, and ADC engineering can now support two binding arms.","test":"Randomised phase 2 with mandatory progression biopsies comparing a bispecific ADC with its parent, with antigen-loss rate as a co-primary endpoint alongside progression-free survival.","maturity":"preclinical-evidence","actor":"industry","cost":"large","horizonYears":6},{"id":"idea-tr2-window-of-opportunity-triplets","kind":"idea","name":"Two-week pre-operative windows to compare combination biology head to head","aka":[],"tldr":"Give patients a short course of one of several drug pairs in the gap before surgery and compare what happened inside the tumours. It is the fastest human test of whether a combination does anything.","summary":"Window-of-opportunity studies give a drug for 1 to 4 weeks between diagnosis and surgery and compare pre- and post-treatment tissue. Multi-arm windows randomising to several combinations with pharmacodynamic endpoints (proliferation, immune infiltration, target pathway suppression) can rank combinations by biological effect in under a year, before any efficacy trial.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Too many combinations to test): Palmer & Sorger, Combination cancer therapy can confer benefit via patient-to-patient variability without drug additivity or synergy (Cell 2017)","url":"https://doi.org/10.1016/j.cell.2017.11.009"}],"tags":[],"related":["idea-tr2-neoadjuvant-combo-platform"],"cancers":["colorectal","head-and-neck"],"sections":[],"technologies":["single-cell-spatial"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-combination-space","b-preclinical-models"],"keyPapers":["paper-palmer-cell"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Combinations ranked highest by pharmacodynamic effect in a multi-arm window study will have higher pathological response rates when taken forward into neoadjuvant trials than lower-ranked ones.","rationale":"Window studies with Ki67 changed endocrine therapy development in breast cancer (POETIC). Multi-arm windows with modern spatial and single-cell readouts can compare combinations mechanistically.","test":"A four-arm window study in resectable colorectal or head and neck cancer with paired biopsies, spatial transcriptomics and a pre-specified pharmacodynamic ranking; follow the top arm into a neoadjuvant trial.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":3},{"id":"idea-fund-translational-fellowships","kind":"idea","name":"Two-year translational fellowships that pay scientists to develop their own discovery","aka":[],"tldr":"Postdocs who make a translatable discovery usually leave it behind when their contract ends. A two-year fellowship with salary, a project budget of $250,000 to $500,000 and mentors from drug development, regulation and the clinic would pay them to turn it into a candidate drug, diagnostic or device, with the option to license it or found a company.","summary":"Fellowships with salary, a project budget of $250,000 to $500,000 and structured mentoring from drug developers, regulatory experts and clinicians, awarded to postdoctoral scientists or clinical fellows to translate a specific finding: target validation, lead optimisation, assay development, prototype device. Fellows are hosted in translational institutes or academic drug discovery units and have the option to found a company or license the asset. Precedents include the Wellcome and MRC translational fellowships, Blavatnik Fellowships and the EMBL-EBI industry programme; oncology lacks a dedicated scheme at scale.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The valley of death between lab and product): Butler, Translational research: crossing the valley of death (Nature 2008)","url":"https://doi.org/10.1038/453840a"}],"tags":[],"related":["idea-fund-translational-institutes-gmp","idea-fund-surgeon-scientist-pathway","idea-fund-protected-time-physician-scientists"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-translational-valley","b-workforce"],"keyPapers":["paper-butler-nature"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Translational fellows advance their assets to a defined milestone (validated target, lead series, IND-enabling start, prototype in patients) in at least half of cases, and a third of assets attract follow-on funding or licensing within two years of the fellowship, versus a small minority of comparable unfunded discoveries.","rationale":"Discoveries are stranded because the people who understand them are on short contracts with incentives to publish and move; paying the discoverer to translate is cheaper than paying a company to rediscover. Existing translational fellowship schemes report high rates of spin-out and licensing.","test":"Run fifty fellowships over three years and pre-register the milestone and follow-on metrics against a matched cohort of discoveries from the same institutions without fellowship support.","maturity":"speculative","actor":"research","cost":"medium","horizonYears":4},{"id":"idea-crc-uk-colonoscopy-capacity-and-fit-threshold","kind":"idea","name":"UK gap: match endoscopy capacity and quality to the faecal immunochemical test thresholds the NHS has already set","aka":[],"tldr":"Every positive stool test in England, from the screening programme and from the symptomatic pathway, ends in a colonoscopy. The thresholds have been lowered faster than the capacity to act on them, and who performs the test decides whether it prevents anything.","summary":"This is a placeholder for the UK-specific analysis written by the UK and NHS file of this deep dive, which owns the programme ages, the symptomatic faecal immunochemical test threshold in NICE NG12, the National Bowel Cancer Audit indicators and the endoscopy workforce figures. The evidence this roadmap can contribute is the general form of the constraint: NordICC showed that a screening programme delivers the effect of its uptake, not of its test, and Kaminski showed a roughly tenfold difference in interval cancer risk between endoscopists with adenoma detection rates below 11 percent and above 20 percent.\n\nThe two levers are therefore capacity, which sets how quickly a positive test reaches a colonoscopy, and quality assurance, which sets whether that colonoscopy finds the adenoma. Neither is a research question in the usual sense, which is why they attract less attention than the trials on the rest of this page.","asOf":"2026-09-24","links":[{"label":"NICE NG12: suspected cancer, recognition and referral","url":"https://www.nice.org.uk/guidance/ng12"},{"label":"National Bowel Cancer Audit (NATCAN)","url":"https://www.natcan.org.uk/audits/bowel/"}],"tags":["colorectal-evidence"],"related":["colorectal-roadmap","early-detection-roadmap"],"cancers":["colorectal"],"sections":["early-detection"],"technologies":["colonoscopy","endoscopy","colorectal-screening","ai-endoscopy-detection"],"targets":[],"drugs":[],"companies":[],"institutions":["nice","cruk"],"pathways":[],"terms":["fit-test"],"trials":[],"people":[],"bottlenecks":["b-workforce","b-early-detection","b-care-fragmentation","b-global-access"],"keyPapers":["paper-kaminski-adenoma-detection-rate-interval-cancer-nejm-2010","paper-nordicc-nejm-2022","paper-atkin-flexible-sigmoidoscopy-17-year-follow-up-lancet-2017"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Aligning endoscopy capacity and endoscopist-level adenoma detection rate accreditation to the faecal immunochemical test thresholds already in use reduces post-colonoscopy colorectal cancer incidence and shortens the interval from positive test to diagnosis, with a larger population effect than any currently funded change in the test itself.","rationale":"Thresholds have moved faster than capacity, and the quality distribution of colonoscopy is wide enough that the same positive test produces very different outcomes depending on who investigates it.","test":"To be specified by the UK and NHS file of this deep dive against National Bowel Cancer Audit and screening programme data: a service evaluation linking regional endoscopy capacity and adenoma detection rate distributions to time from positive test to diagnosis, stage at diagnosis and post-colonoscopy colorectal cancer rates.","maturity":"being-tested-at-scale","actor":"policy","cost":"large","horizonYears":4},{"id":"idea-crc-uk-young-patient-referral-and-diagnostic-interval","kind":"idea","name":"UK gap: shorten the route to diagnosis for patients below the screening age, where the rise in incidence is","aka":[],"tldr":"The fastest rise in bowel cancer is in people two decades younger than any screening programme, who reach diagnosis through symptoms, often after several visits. Screening cannot help them; the referral pathway can.","summary":"This is a placeholder for the UK-specific analysis written by the UK and NHS file of this deep dive, which owns the NICE NG12 referral criteria, the symptomatic faecal immunochemical test threshold, the faster diagnosis standard and the National Bowel Cancer Audit's route-to-diagnosis data. The evidence this roadmap contributes is the shape of the problem: incidence in people aged 20 to 29 rose 7.9 percent a year across 20 European countries between 2004 and 2016, the proportion of United States rectal cancers diagnosed under 55 doubled to 29.2 percent, and 60 percent of new cases were advanced at diagnosis in 2019 against 52 percent in the mid-2000s.\n\nBecause these patients are below every screening age, the only lever is the symptomatic pathway: how a young adult with rectal bleeding or a change in bowel habit is triaged, whether a faecal immunochemical test is used to rule out rather than to delay, and how many primary care contacts precede referral.","asOf":"2026-09-24","links":[{"label":"NICE NG12: suspected cancer, recognition and referral","url":"https://www.nice.org.uk/guidance/ng12"},{"label":"National Bowel Cancer Audit (NATCAN)","url":"https://www.natcan.org.uk/audits/bowel/"}],"tags":["colorectal-evidence"],"related":["colorectal-roadmap","idea-crc-early-onset-cause-hunt"],"cancers":["colorectal","early-onset-colorectal","rectal-cancer"],"sections":["early-detection"],"technologies":["colorectal-screening","colonoscopy"],"targets":[],"drugs":[],"companies":[],"institutions":["nice","cruk"],"pathways":[],"terms":["fit-test"],"trials":[],"people":[],"bottlenecks":["b-early-detection","b-care-fragmentation","b-knowledge-diffusion"],"keyPapers":["paper-vuik-early-onset-colorectal-europe-gut-2019","paper-siegel-colorectal-incidence-birth-cohort-jnci-2017","paper-siegel-colorectal-cancer-statistics-ca-2023"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"An age-aware symptomatic pathway for patients under 50 (explicit safety-netting, a faecal immunochemical test used as a rule-out with a defined follow-up, and direct-access investigation after a specified number of contacts) reduces the interval from first presentation to diagnosis and the proportion diagnosed as an emergency, without a material increase in colonoscopy demand.","rationale":"Early-onset cases present symptomatically and later-stage; the pathway, not the screening programme, is the only mechanism available to them, and route-to-diagnosis data already show emergency presentation is commoner in this group.","test":"To be specified by the UK and NHS file of this deep dive: a service evaluation against National Bowel Cancer Audit route-to-diagnosis and faster diagnosis standard data, followed by a cluster-randomised trial of the age-aware pathway in primary care networks, with time to diagnosis and stage at diagnosis as primary outcomes.","maturity":"early-clinical","actor":"policy","cost":"medium","horizonYears":4},{"id":"idea-thyroid-overdiagnosis-reversal","kind":"idea","name":"Ultrasound restraint and surveillance to reverse thyroid cancer overdiagnosis","aka":[],"tldr":"Most thyroid cancers found today would never have hurt anyone. Screen less, watch small ones, and operate only when they grow.","summary":"The idea is that health systems can reverse thyroid cancer overdiagnosis by screening less with ultrasound, adopting TI-RADS thresholds for biopsy, and placing papillary cancers of 1 cm or less under active surveillance, operating only when they grow. Incidence has tripled in many countries since the 1990s while deaths stayed flat, autopsies find occult papillary cancer in many adults, and the Kuma Hospital and MSK cohorts show surveillance is safe. The hypothesis is that these policies can halve thyroidectomy rates without increasing thyroid cancer deaths; South Korea's screening-driven epidemic reversed once screening was discouraged. The test is registry comparison before and after policy change; the idea addresses the overdiagnosis bottleneck.","asOf":"2026-09-07","links":[{"label":"Ahn et al., Korea's thyroid cancer epidemic: screening and overdiagnosis (NEJM 2014)","url":"https://doi.org/10.1056/NEJMp1409841"}],"tags":[],"related":[],"cancers":["thyroid"],"sections":[],"technologies":["active-surveillance-thyroid","thyroid-fna-molecular","ultrasound"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-ahn-n-engl-j-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Health systems adopting TI-RADS biopsy thresholds and active surveillance for ≤1 cm papillary cancers can halve thyroidectomy rates without increasing thyroid cancer mortality.","rationale":"Autopsy studies find occult papillary cancer in up to a third of adults; Kuma Hospital and MSK cohorts show safety of surveillance.","test":"Regional registry comparisons before and after policy change (South Korea already provides a natural experiment); prospective surveillance cohorts outside Asia.","maturity":"being-tested-at-scale"},{"id":"idea-bio2-sonobiopsy","kind":"idea","name":"Ultrasound-assisted blood test instead of a brain biopsy","aka":[],"tldr":"Brain tumours release little DNA into blood because of the blood-brain barrier. Sonobiopsy briefly opens the barrier with focused ultrasound and microbubbles, raising circulating tumour DNA severalfold so a blood sample can replace repeat surgical biopsy for diagnosis and resistance monitoring in glioma and brain metastases.","summary":"Focused ultrasound with microbubbles transiently opens the blood-brain barrier, and first-in-human sonobiopsy studies report severalfold increases in circulating tumour DNA and brain-derived proteins after sonication, without lasting damage. This could replace repeat surgical biopsy for molecular diagnosis, resistance monitoring and response assessment in glioma and brain metastases.","asOf":"2026-09-08","links":[{"label":"Focused Ultrasound Foundation","url":"https://www.fusfoundation.org"}],"tags":[],"related":[],"cancers":["glioblastoma"],"sections":[],"technologies":["bbb-focused-ultrasound","liquid-biopsy","mrd-testing"],"targets":[],"drugs":[],"companies":["insightec"],"institutions":[],"pathways":[],"terms":["blood-brain-barrier","ctdna"],"trials":[],"people":[],"bottlenecks":["b-brain-delivery","b-tumor-heterogeneity"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Focused ultrasound sonication before blood sampling raises the detection rate of tumour-specific mutations in plasma from under 20% to over 70% in glioma, with no grade 3 adverse events.","rationale":"The barrier is the reason brain tumour liquid biopsy fails, and opening it is now a routine procedure in movement disorder and Alzheimer's trials. Diagnostic use requires only transient opening, which is a lower safety bar than drug delivery.","test":"A prospective study in patients undergoing planned resection: sonobiopsy plasma versus tissue as reference standard, reporting sensitivity, specificity and safety.","maturity":"early-clinical","actor":"engineering","cost":"medium","horizonYears":5},{"id":"idea-moon-universal-sequencing-learning-system","kind":"idea","name":"Universal tumour and germline sequencing at diagnosis feeding a shared learning system","aka":[],"tldr":"Sequence every cancer at diagnosis, along with the patient's inherited genes, and pool the results with treatments and outcomes so every patient teaches the system how to treat the next.","summary":"Comprehensive genomic profiling reaches a minority of patients even in rich countries, and results rarely rejoin outcome data. Genomics England, AACR Project GENIE and national programmes in the Netherlands and Denmark show what pooled genomics plus outcomes can do. The proposal is universal whole-genome or comprehensive panel sequencing plus germline testing at diagnosis as a funded standard, with mandatory return of de-identified genomic, treatment and outcome data to a federated national learning system that publishes evidence for rare variants, drug response and hereditary risk.","asOf":"2026-09-08","links":[{"label":"AACR Project GENIE","url":"https://www.aacr.org/professionals/research/aacr-project-genie/"},{"label":"Genomics England","url":"https://www.genomicsengland.co.uk/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["wes-wgs","cgp","germline-testing"],"targets":[],"drugs":[],"companies":[],"institutions":["aacr"],"pathways":[],"terms":["real-world-evidence","germline-vs-somatic"],"trials":[],"people":[],"bottlenecks":["b-data-silos","b-real-world-evidence","b-hereditary-risk"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Within five years the learning system produces at least ten practice-changing findings not obtainable from trials (rare variant actionability, real-world resistance patterns) and increases the fraction of patients receiving matched therapy or hereditary cascade testing.","rationale":"Genomic actionability grows with the number of observed cases, and rare events only become interpretable at population scale; the marginal cost of sequencing is now small relative to treatment.","test":"National programme in one health system with sequencing coverage, matched therapy rates, cascade testing and time to new actionable findings as endpoints.","maturity":"being-tested-at-scale","actor":"policy","cost":"large","horizonYears":5},{"id":"idea-fund-global-access-licensing-royalties","kind":"idea","name":"University licences with royalties indexed to benefit and global access","aka":[],"tldr":"When universities license cancer discoveries to companies, the contract would reward companies that price fairly and sell in poor countries, and penalise those that do not, using the royalty rate as the lever.","summary":"Technology transfer offices adopt a standard licence for oncology inventions in which the royalty rate steps down when the licensee meets access conditions (registration and tiered pricing in a list of low- and middle-income countries within two years of first approval, non-exclusive licensing to the Medicines Patent Pool for those markets) and steps up if the launch price exceeds a value-based reference. Since a large share of first-in-class cancer drugs originate in academic labs (including the checkpoint inhibitors and CAR-T), universities collectively hold leverage they rarely use. Universities Allied for Essential Medicines has drafted model clauses; the change is to make them the default for cancer.","asOf":"2026-09-08","links":[{"label":"Universities Allied for Essential Medicines","url":"https://www.uaem.org/"},{"label":"Medicines Patent Pool","url":"https://medicinespatentpool.org/"}],"tags":[],"related":["idea-fund-conditional-transferable-voucher","idea-fund-health-impact-fund-oncology","idea-fund-combination-patent-pool"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-incentive-misalignment","b-global-access","b-ip-collaboration"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"If twenty leading research universities adopt indexed licences, oncology drugs derived from their patents are registered in at least twice as many low- and middle-income countries within three years of first approval as comparable drugs, with no measurable fall in licensing deal flow.","rationale":"Yale's licence for stavudine and subsequent global-access licensing (for example Medicines Patent Pool licences for hepatitis C and HIV drugs) show that upstream terms can determine downstream access; the royalty step is a low-cost, self-enforcing mechanism.","test":"A consortium of universities adopts the licence for all new oncology deals; compare registration breadth and pricing of resulting products with a matched historical cohort after five years.","maturity":"speculative","actor":"policy","cost":"small","horizonYears":4},{"id":"idea-bio2-epigenetic-priming-cold-tumours","kind":"idea","name":"Unmask hidden antigens with a short epigenetic course before immunotherapy","aka":[],"tldr":"Low doses of drugs that change how DNA is packaged can make cancer cells display more of what marks them as abnormal, potentially waking up immunotherapy in cold tumours.","summary":"Hypomethylating agents de-repress endogenous retroviruses and cancer-testis antigens and induce viral mimicry through interferon signalling, and HDAC or EZH2 inhibition can restore antigen presentation machinery. Trials combining epigenetic agents with checkpoint blockade in colorectal and lung cancer have been mostly small, with variable schedules and no pharmacodynamic gating. Dose and schedule, rather than the concept, are probably the reason for inconsistency.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (No one can predict who responds to immunotherapy): Haslam & Prasad (JAMA Network Open 2019)","url":"https://doi.org/10.1001/jamanetworkopen.2019.2535"}],"tags":[],"related":["idea-immunotherapy-mss-crc"],"cancers":["colorectal","nsclc"],"sections":[],"technologies":["epigenetic-drugs","checkpoint-inhibitor","methylation-profiling"],"targets":["ezh2"],"drugs":["azacitidine","decitabine-cedazuridine","mevrometostat"],"companies":[],"institutions":[],"pathways":[],"terms":["msi","cold-vs-hot"],"trials":[],"people":[],"bottlenecks":["b-immunotherapy-response","b-tme-immunosuppression","b-combination-space"],"keyPapers":["paper-haslam-jama-netw-open","paper-ezh2-colorectal-br-j-cancer-2009"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A pharmacodynamically gated low-dose epigenetic priming schedule, confirmed by an interferon signature and antigen re-expression on biopsy, raises response to checkpoint blockade in mismatch-repair-proficient colorectal cancer above the near-zero baseline.","rationale":"Viral mimicry is a well-replicated mechanism in human cells, and the constraint is achieving priming exposure without lymphotoxicity. Gating escalation on a measured interferon response is the discipline previous combination trials lacked.","test":"A phase 1b with mandatory paired biopsies where dose escalation is gated on interferon signature induction rather than tolerability alone, and expansion only if priming is demonstrated.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":6},{"id":"idea-data-order-set-defaults-30-days","kind":"idea","name":"Update hospital order sets within 30 days of a guideline change","aka":[],"tldr":"The pre-built treatment menus in hospital computers often stay unchanged for years. Require them to be updated within a month of any guideline change, using the machine-readable guideline feed.","summary":"Order sets and chemotherapy protocol libraries are the actual determinant of what gets prescribed, and they are updated by local committees on their own schedule. The proposal ties protocol libraries to the computable guideline feed with a 30-day service-level requirement, tracked and published per centre, and provides shared, validated protocol content (as the Cancer Care Ontario and NHS regimen libraries do) so each centre does not rebuild it.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Knowledge reaches practice too slowly): Morris, Wooding & Grant, The answer is 17 years, what is the question (JRSM 2011)","url":"https://doi.org/10.1258/jrsm.2011.110180"}],"tags":[],"related":["idea-data-computable-living-guidelines","idea-data-guideline-concordance-dashboards"],"cancers":[],"sections":["ai-computation"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-knowledge-diffusion"],"keyPapers":["paper-morris-j-r-soc-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Centres meeting a 30-day order-set update requirement will show adoption of new standards months earlier than centres with ad hoc updates, measured in structured prescribing data.","rationale":"Default options strongly shape prescribing; changing the default is the cheapest and most effective implementation lever available, and it is currently unmanaged.","test":"Measure order-set update latency for the last five practice changes across 30 centres; implement the requirement with shared content in half; compare adoption curves.","maturity":"early-clinical","actor":"clinic","cost":"small","horizonYears":1},{"id":"idea-acc-upfront-reduced-dose-trials-frail","kind":"idea","name":"Upfront reduced-dose regimens tested head-to-head in frail older patients","aka":[],"tldr":"Frail older patients are often given full doses and then have them cut after bad side effects, or are given nothing. Trials should test starting at a lower dose from the beginning.","summary":"The GO2 trial in frail patients with advanced gastro-oesophageal cancer showed that the lowest of three chemotherapy dose levels gave non-inferior progression-free survival with better patient experience. This design, comparing upfront dose levels rather than escalating after toxicity, is rarely used elsewhere. A programme of GO2-style trials across common cancers would give evidence for the many frail patients for whom current guidelines offer only extrapolation.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Older and multimorbid patients are excluded and undertreated): Mohile et al., Evaluation of geriatric assessment and management on toxic effects of cancer treatment (GAP70+, Lancet 2021)","url":"https://doi.org/10.1016/S0140-6736(21)01789-X"}],"tags":[],"related":[],"cancers":["gastric","esophageal","colorectal"],"sections":[],"technologies":["cytotoxic-chemotherapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-aging-comorbidity","b-dose-optimisation","b-trial-design"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"In at least three common indications, an upfront reduced-dose regimen will be non-inferior for survival and superior for quality of life and treatment completion in frail older patients.","rationale":"GO2 provides a template; toxicity-driven dose reduction in practice means many patients already receive lower doses without evidence about which starting level is best.","test":"Fund three GO2-style randomised dose-level trials in frail older patients with lung, colorectal, and breast cancer, with overall treatment utility as a co-primary endpoint.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":4},{"id":"idea-urine-ctdna-surveillance","kind":"idea","name":"Urine tumour DNA to replace surveillance cystoscopy in NMIBC","aka":[],"tldr":"Bladder cancer sheds tumour DNA straight into urine. A urine test every few months could replace part of the surveillance cystoscopy schedule that patients with non-muscle-invasive bladder cancer follow for years, doubling the interval between camera examinations when the test is negative.","summary":"Bladder cancer sheds tumour DNA directly into urine, and this idea proposes a urine test to replace part of the surveillance cystoscopy schedule that patients with non-muscle-invasive bladder cancer follow for years. Assays such as UroAmp, Bladder EpiCheck, Cxbladder and methylation panels detect recurrence with sensitivity approaching cystoscopy and can anticipate it by months. The rationale is that urine carries a far higher tumour DNA fraction than plasma, and that cystoscopy burden and cost make bladder cancer the most expensive cancer per patient. The hypothesis is that a negative urine test allows cystoscopy intervals to be doubled in intermediate-risk disease without more progression, tested in a randomised trial against fixed-interval cystoscopy, at an early clinical stage.","asOf":"2026-09-07","links":[{"label":"Dudley et al., Detection and surveillance of bladder cancer using urine tumour DNA (Cancer Discovery 2019)","url":"https://doi.org/10.1158/2159-8290.CD-18-0825"}],"tags":[],"related":[],"cancers":["urothelial"],"sections":[],"technologies":["liquid-biopsy","mrd-testing","cystoscopy-turbt"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-dudley-cancer-discov"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A negative urine tumour DNA test allows cystoscopy intervals to be doubled in intermediate-risk NMIBC without an increase in progression to MIBC.","rationale":"Urine has far higher tumour DNA fraction than plasma for bladder cancer; cystoscopy burden and cost are the main drivers of bladder cancer's status as the most expensive cancer per patient.","test":"Randomised trial of urine-guided vs fixed-interval cystoscopy with progression as primary endpoint and quality of life secondary.","maturity":"early-clinical"},{"id":"idea-bio2-ctdna-six-week-io-switch","kind":"idea","name":"Use a blood test at six weeks to decide whether to keep going","aka":[],"tldr":"Scans at three months often cannot tell whether immunotherapy is working. A blood test at six weeks may give a clearer, earlier answer.","summary":"On-treatment ctDNA change at four to eight weeks predicted checkpoint outcomes across tumour types in several cohorts, including pan-cancer analyses, and outperformed early imaging in distinguishing pseudoprogression from true progression. The step never taken is a randomised trial in which the ctDNA result actually drives the decision to continue, intensify or switch.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (No one can predict who responds to immunotherapy): Haslam & Prasad (JAMA Network Open 2019)","url":"https://doi.org/10.1001/jamanetworkopen.2019.2535"}],"tags":[],"related":["idea-cd8-pet-io","idea-ctdna-switch-generalised"],"cancers":["nsclc","melanoma","urothelial"],"sections":[],"technologies":["liquid-biopsy","mrd-testing","checkpoint-inhibitor"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["ctdna","recist","pfs"],"trials":[],"people":[],"bottlenecks":["b-immunotherapy-response","b-drug-pricing","b-trial-design"],"keyPapers":["paper-haslam-jama-netw-open"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A ctDNA-guided switch strategy at six weeks improves overall survival compared with imaging-guided management, by moving non-responders onto alternative therapy months earlier.","rationale":"Molecular response precedes radiographic response, and the cost of continuing an ineffective checkpoint inhibitor is measured in months of lost opportunity as well as money. Interventional ctDNA guidance has already proved feasible in the adjuvant setting.","test":"A randomised strategy trial in advanced disease comparing ctDNA-guided with standard imaging-guided management, with overall survival as primary endpoint and drug cost as a pre-specified secondary.","maturity":"early-clinical","actor":"clinic","cost":"medium","horizonYears":4},{"id":"idea-bio2-hypoxia-guided-adenosine","kind":"idea","name":"Use a hypoxia scan to pick patients for adenosine-pathway drugs","aka":[],"tldr":"Tumours starved of oxygen produce a chemical that switches immune cells off. A scan can show which tumours are starved, and those are the ones to treat with blockers.","summary":"Hypoxia drives CD73-mediated adenosine production and A2A receptor signalling that suppresses T cells and natural killer cells. Adenosine-axis drugs have given inconsistent phase 2 results in unselected populations. Hypoxia PET tracers and validated hypoxia gene signatures could select the patients whose tumours actually run this pathway.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Cold tumours and the immunosuppressive microenvironment): Haslam & Prasad, Estimation of the percentage of US patients eligible for and responding to checkpoint inhibitors (JAMA Netw Open 2019)","url":"https://doi.org/10.1001/jamanetworkopen.2019.2535"}],"tags":[],"related":[],"cancers":["rcc","nsclc","prostate"],"sections":[],"technologies":["pet","checkpoint-inhibitor","rna-seq"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["hif-vhl"],"terms":[],"trials":[],"people":[],"bottlenecks":["b-tme-immunosuppression","b-immunotherapy-response","b-biomarker-validation"],"keyPapers":["paper-haslam-jama-netw-open"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Adenosine-axis blockade improves response only in patients whose tumours are hypoxia-high by imaging or signature, and pooling hypoxia-low patients accounts for previous inconsistent results.","rationale":"Adenosine generation is mechanistically downstream of hypoxia, so a hypoxia biomarker is causally, not merely statistically, linked to drug relevance. Hypoxia imaging and signatures are mature research tools ready for prospective use.","test":"Retrospective interaction analysis of hypoxia signatures in completed adenosine-axis trials; if the interaction holds, run a prospectively hypoxia-selected randomised phase 2.","maturity":"early-clinical","actor":"industry","cost":"medium","horizonYears":5},{"id":"idea-prev-prs-screening-start-age","kind":"idea","name":"Use a polygenic risk score to set when screening starts","aka":[],"tldr":"Common gene variants shift a person's cancer risk several-fold. A one-time genetic score could tell each person when to start breast, bowel or prostate screening.","summary":"Polygenic scores reclassify risk for breast, prostate, and colorectal cancer, and BARCODE1 showed PRS-selected prostate screening finds clinically significant disease. Propose national programmes assigning screening start age by PRS plus family history, with a pragmatic trial comparing PRS-tailored to age-based invitation.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Inherited risk is mostly unidentified): Childers et al., National estimates of genetic testing in women with breast or ovarian cancer (JCO 2017)","url":"https://doi.org/10.1200/JCO.2017.73.6314"}],"tags":[],"related":["prostate-roadmap","idea-prostate-metastatic-presentation-as-the-screening-endpoint"],"cancers":["breast-hr-positive","prostate","colorectal","early-onset-colorectal"],"sections":["prevention","early-detection"],"technologies":["germline-testing"],"targets":[],"drugs":[],"companies":[],"institutions":["icr-london"],"pathways":[],"terms":["polygenic-risk-score"],"trials":[],"people":[],"bottlenecks":["b-hereditary-risk","b-early-detection"],"keyPapers":["paper-childers-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"PRS-tailored start ages detect the same number of cancers with at least 15% fewer screening tests and earlier detection in the top PRS decile.","rationale":"Risk in the top polygenic decile at 40 roughly equals population risk at 50; screening efficiency scales with risk.","test":"Embedded trial in a national programme with PRS returned through an Our Future Health-style cohort.","maturity":"early-clinical","actor":"policy","cost":"large","horizonYears":6},{"id":"idea-bio1-antibody-degrader-conjugates","kind":"idea","name":"Use antibodies to deliver protein-destroying drugs into the right cells","aka":[],"tldr":"Drugs that destroy proteins can hit healthy cells too. Attaching them to an antibody that only docks onto tumour cells would keep them where they are needed.","summary":"Degrader-antibody conjugates replace cytotoxic payloads with a targeted protein degrader, so the payload is only released inside antigen-positive cells. Early programmes target BRD4 and other essential proteins that are too toxic to degrade systemically. This is a route to attack undruggable but essential nuclear proteins that would otherwise be intolerable.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The undruggable drivers): Dang et al., Drugging the 'undruggable' cancer targets (Nature Reviews Cancer 2017)","url":"https://doi.org/10.1038/nrc.2017.36"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["degrader-antibody-conjugate","adc","protac-degrader"],"targets":[],"drugs":[],"companies":["kymera","nurix","sutro-biopharma"],"institutions":[],"pathways":[],"terms":["payload","bystander-effect"],"trials":[],"people":[],"bottlenecks":["b-undruggable-targets","b-toxicity-qol"],"keyPapers":["paper-dang-nat-rev-cancer"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A degrader-antibody conjugate produces antigen-dependent degradation of an essential nuclear target in vivo with a therapeutic window at least five-fold wider than the free degrader.","rationale":"ADC linker and payload technology is mature; the constraint on degrading essential proteins is normal-tissue exposure, exactly the problem conjugation solves. Bystander effects may also address antigen heterogeneity.","test":"Compare matched free degrader and conjugate in an antigen-positive versus antigen-negative xenograft pair, with tumour and normal-tissue degradation pharmacodynamics and marrow toxicity as endpoints.","maturity":"preclinical-evidence","actor":"industry","cost":"medium","horizonYears":6},{"id":"lymphoma-ev-ctdna-instead-of-the-interim-scan","kind":"idea","name":"Use circulating tumour DNA instead of the interim scan to decide what happens next","aka":["Molecular response-adapted lymphoma therapy","ctDNA-guided de-escalation in lymphoma"],"tldr":"A blood test detects lymphoma left behind better than a scan does, and no trial has yet used it to change anyone's treatment.","summary":"The practical barriers are assay standardisation and turnaround. Commercial implementations differ in sensitivity and in which mutations they track, and a result that arrives after the next cycle has started cannot direct anything. The scientific barrier is that detecting residual disease is not the same as knowing what to do about it: HD16 showed that a negative interim scan does not mean radiotherapy is unnecessary, and a negative molecular test may turn out to mean the same thing.","asOf":"2026-10-01","links":[],"tags":["lymphoma-evidence"],"related":["lymphoma-roadmap","ctdna-tests"],"cancers":["dlbcl","non-hodgkin-lymphoma","hodgkin-lymphoma","early-stage-classical-hodgkin-lymphoma","follicular-lymphoma"],"sections":["diagnostics","early-detection"],"technologies":["liquid-biopsy","ngs","pet-ct"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["ctdna","mrd","deauville-score"],"trials":[],"people":[],"bottlenecks":["b-dormancy-mrd","b-biomarker-validation","b-trial-design"],"keyPapers":["paper-scherer-ctdna-lymphoma-subtypes-genome-evolution-sci-transl-med-2016","paper-kurtz-j-clin-oncol","paper-kurtz-nat-biotechnol","paper-ghsg-hd16-pet-guided-early-favourable-hodgkin-jco-2019"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Treatment adapted to circulating tumour DNA after one or two cycles, rather than to a positron emission tomography scan after two, improves the balance of cure and toxicity in aggressive lymphoma and in Hodgkin lymphoma.","rationale":"Scherer showed that circulating tumour DNA at diagnosis independently predicts outcome, that tracking multiple mutations outperforms imaging for minimal residual disease, and that plasma genotyping reads cell of origin without a biopsy. Kurtz showed it predicts outcome early in treatment. Meanwhile the interim scan has clear limits: it directs intensification well (EORTC H10, hazard ratio 0.42 in scan-positive patients) and de-escalation badly, with HD16 losing 7.3 percentage points of progression-free survival when radiotherapy was omitted on a negative scan. A more sensitive measure of residual disease is the obvious candidate to make de-escalation safe.","test":"A randomised trial in early-stage Hodgkin lymphoma or limited-stage diffuse large B-cell lymphoma comparing treatment adapted to circulating tumour DNA with treatment adapted to the interim scan, powered for non-inferiority on progression-free survival with radiotherapy exposure, cumulative chemotherapy dose and patient-reported outcomes as co-primary. A positive result requires that the molecular test identifies patients who can safely have less, which the scan does not.","maturity":"early-clinical","actor":"research","cost":"large","horizonYears":7},{"id":"idea-tr1-food-effect-dose-reduction","kind":"idea","name":"Use food effects to cut the dose and cost of oral drugs that absorb better with meals","aka":[],"tldr":"Some cancer pills are absorbed several times better with food, but the label says take them fasting at a high dose. Taking a quarter of the dose with breakfast can give the same drug levels at a quarter of the price.","summary":"Randomised PK and non-inferiority trials of low-dose-with-food versus standard fasting dosing for oral agents with large positive food effects (abiraterone is the established example; others include several kinase inhibitors), followed by label changes and guideline adoption. Regulators accept PK-bridged non-inferiority; payers fund the trials because savings are immediate.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Wrong doses): FDA Oncology Center of Excellence, Project Optimus","url":"https://www.fda.gov/about-fda/oncology-center-excellence/project-optimus"}],"tags":[],"related":[],"cancers":["prostate"],"sections":[],"technologies":["kinase-inhibitors","androgen-deprivation"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-dose-optimisation","b-drug-pricing"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Low-dose-with-food regimens will show equivalent exposure and non-inferior efficacy for most agents with a fourfold or greater food effect, cutting drug cost by 50-75 percent.","rationale":"Fasting dosing was chosen to reduce variability, not to maximise benefit; for drugs whose absorption is limited fasting, feeding is a cheap way to increase exposure, and the variability concern can be tested directly.","test":"Identify candidates from label PK data; run PK-bridged randomised non-inferiority trials for the two with the largest spend, with a pre-agreed pathway to label change.","maturity":"early-clinical","actor":"research","cost":"small","horizonYears":2},{"id":"idea-bio2-vascular-normalisation-window","kind":"idea","name":"Use imaging to find the window when tumour blood vessels are working properly","aka":[],"tldr":"Low doses of anti-blood-vessel drugs briefly make tumour vessels work better, which helps immune cells and other drugs get in. Scans can find that window for each patient.","summary":"Vascular normalisation after low-dose anti-angiogenic therapy is transient and dose-dependent, and DCE-MRI or perfusion CT can measure it patient by patient. Current anti-angiogenic and checkpoint combinations use fixed high doses and fixed schedules, so many patients are likely dosed outside their own normalisation window. Imaging-guided scheduling is a trial design intervention with existing drugs.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Cold tumours and the immunosuppressive microenvironment): Haslam & Prasad, Estimation of the percentage of US patients eligible for and responding to checkpoint inhibitors (JAMA Netw Open 2019)","url":"https://doi.org/10.1001/jamanetworkopen.2019.2535"}],"tags":[],"related":["io-plus-vegf"],"cancers":[],"sections":[],"technologies":["antiangiogenic","mri","checkpoint-inhibitor","pet"],"targets":[],"drugs":["bevacizumab","lenvatinib"],"companies":[],"institutions":[],"pathways":["vegf-angiogenesis"],"terms":[],"trials":[],"people":[],"bottlenecks":["b-tme-immunosuppression","b-dose-optimisation"],"keyPapers":["paper-haslam-jama-netw-open"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Timing checkpoint or cytotoxic administration to an imaging-defined perfusion peak increases intratumoural drug delivery and T-cell infiltration compared with fixed scheduling.","rationale":"Normalisation is well documented in human rectal and glioblastoma studies where perfusion improvement correlated with outcome. Scheduling is free, and imaging endpoints read out in days rather than months.","test":"A randomised imaging-guided versus fixed-schedule window trial with intratumoural drug concentration or CD8 density as the primary endpoint in an accessible tumour.","maturity":"early-clinical","actor":"clinic","cost":"medium","horizonYears":5},{"id":"idea-bio2-let-rbe-ab-selects-protons","kind":"idea","name":"Use LET, RBE and alpha/beta to decide when protons beat IMRT","aka":[],"tldr":"Protons cost more than shaped X-ray beams. They are worth it when the extra punch where the beam stops, and the missing exit dose, widen the gap between killing the tumour and harming late-reacting tissue: an alpha/beta and RBE question, not a machine question.","summary":"Adult proton versus photon randomised trials have mixed toxicity results and scarce survival differences. Plans are still reported at a constant RBE of 1.1. The biological reason protons could win is site-specific: a low-alpha/beta tumour next to a low-alpha/beta late organ, plus high linear energy transfer at a distal edge that can be kept inside the target and off the organ. That predicted window should be written down before the trial reads out. The coverage-with-evidence idea asks payers to fund the trials; this idea asks the trials to test the radiobiology, not only the machine.","asOf":"2026-09-08","links":[{"label":"Paganetti, RBE values for proton beam therapy (IJROBP 2014)","url":"https://doi.org/10.1016/j.ijrobp.2014.07.001"},{"label":"PARTIQoL (NCT01617161)","url":"https://clinicaltrials.gov/study/NCT01617161"},{"label":"RADCOMP (NCT02603341)","url":"https://clinicaltrials.gov/study/NCT02603341"}],"tags":["radiation-wave5"],"related":["idea-fund-proton-coverage-with-evidence","proton-vs-imrt"],"cancers":["prostate","breast-hr-positive","esophageal","nsclc"],"sections":["radiation"],"technologies":["proton-therapy","imrt-igrt","carbon-ion","linear-quadratic-model","intensity-modulated-proton-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["linear-energy-transfer","relative-biological-effectiveness","alpha-beta-ratio","bragg-peak","biologically-effective-dose"],"trials":["partiqol","radcomp"],"people":[],"bottlenecks":["b-surgery-radiation-innovation"],"keyPapers":["paper-paganetti-proton-rbe-ijrobp-2014"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Pre-specifying tissue alpha/beta and a variable-RBE (LET-weighted) proton plan predicts which anatomies will show less late toxicity at equal tumour control in proton-versus-IMRT randomised trials. A constant 1.1 RBE plan will not.","rationale":"Constant RBE 1.1 is a reporting convention. Variable RBE rises at the distal edge and is larger for low-alpha/beta late tissues. If that physics does not show up in PARTIQoL, RADCOMP and the NRG oesophageal and lung comparisons, the adult proton case rests only on integral-dose and second-cancer arguments, not on a wider therapeutic window for the index tumour.","test":"On PARTIQoL (prostate), RADCOMP (breast), and the NRG/Lin oesophageal proton-versus-photon trials, lock an alpha/beta pair and an LET-weighted RBE model before unblinding the late-toxicity analysis, and ask whether the predicted window matches the result. A miss is as informative as a hit.","maturity":"preclinical-evidence","actor":"research","cost":"small","horizonYears":5},{"id":"idea-bio1-organoid-cell-therapy-potency","kind":"idea","name":"Use patient organoids to check a cell therapy will work before infusing it","aka":[],"tldr":"Cell therapies are tested for purity and count, but not for whether they can actually kill that patient's tumour. Testing them against the patient's own mini-tumour would show this.","summary":"Release criteria for CAR-T and TIL products measure viability, transduction and sterility, not tumour-specific cytotoxicity. Co-culturing an aliquot of the product with the patient's own organoid or tumour slice gives a functional potency assay with a killing readout. This could flag likely non-responders before lymphodepletion, and provide a comparator when choosing between products or targets.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Lab models that fail to predict what happens in patients): Wong, Siah & Lo, Estimation of clinical trial success rates (Biostatistics 2019)","url":"https://doi.org/10.1093/biostatistics/kxx069"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["organoids","car-t","til-therapy"],"targets":[],"drugs":["lifileucel"],"companies":["iovance"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-preclinical-models","b-manufacturing-cell-therapy"],"keyPapers":["paper-wong-biostatistics"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Ex vivo killing of the patient's own organoid by the manufactured product predicts clinical response, and products failing a defined potency threshold have a markedly lower response rate.","rationale":"Product potency varies widely and correlates with T-cell fitness in reported series; a patient-specific functional assay is the most direct measure and can be run during the manufacturing window.","test":"Prospective blinded correlation in 60 patients receiving CAR-T or TIL therapy, comparing organoid killing scores with response at three months.","maturity":"speculative","actor":"research","cost":"medium","horizonYears":4},{"id":"idea-bio2-neoadjuvant-biomarker-engine","kind":"idea","name":"Use pre-surgery immunotherapy windows as the field's biomarker engine","aka":[],"tldr":"Giving immunotherapy for a few weeks before surgery produces a tumour sample that shows exactly what the drug did. That is the fastest way to learn who responds.","summary":"Neoadjuvant window trials deliver paired baseline and post-treatment tissue plus a pathological response readout within weeks, and they have already produced high-quality mechanistic insight in melanoma, colorectal cancer with mismatch repair deficiency and bladder cancer. Standardising a shared window protocol across tumour types, with common tissue handling and open data release, would turn scattered studies into a systematic discovery platform.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (No one can predict who responds to immunotherapy): Haslam & Prasad (JAMA Network Open 2019)","url":"https://doi.org/10.1001/jamanetworkopen.2019.2535"}],"tags":[],"related":[],"cancers":["colorectal","melanoma","urothelial"],"sections":[],"technologies":["checkpoint-inhibitor","single-cell-spatial","rna-seq"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["major-pathological-response","pcr","neoadjuvant-adjuvant"],"trials":["niche-2","nadina","checkmate-816"],"people":["myriam-chalabi","christian-blank"],"bottlenecks":["b-immunotherapy-response","b-trial-design","b-negative-results"],"keyPapers":["paper-haslam-jama-netw-open"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A standardised multi-tumour neoadjuvant window platform identifies and validates response biomarkers at least twice as fast as advanced-disease trials, measured by biomarkers reaching prospective validation per year.","rationale":"Pathological response is available in weeks and correlates with long-term outcome in several diseases, so causal inference is far cheaper than in metastatic trials. Neoadjuvant mismatch repair deficient studies produced near-complete response rates and detailed mechanism from small numbers of patients.","test":"Launch a shared window protocol at ten centres across three tumour types with common sample processing and mandatory rapid open data release; measure biomarkers nominated and validated per year.","maturity":"being-tested-at-scale","actor":"research","cost":"medium","horizonYears":4},{"id":"idea-bio2-mrd-guided-endocrine-duration","kind":"idea","name":"Use residual disease tests to decide who needs ten years of hormone therapy","aka":[],"tldr":"Extended hormone therapy after breast cancer prevents late recurrence in a minority of women while imposing joint pain, bone loss and sexual side-effects on everyone for a decade. A sensitive residual disease blood test at year five, repeated annually, could show who can safely stop.","summary":"Extended adjuvant endocrine therapy prevents late recurrence in a minority while imposing joint pain, bone loss and sexual side-effects on everyone. Sensitive MRD testing at year five, repeated annually, could identify the persistently negative majority in whom continuation adds little, while intensifying treatment for the positive minority. This inverts the usual escalation-only use of MRD.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Dormant cells and minimal residual disease): Tie et al., ctDNA analysis guiding adjuvant therapy in stage II colon cancer (NEJM 2022)","url":"https://doi.org/10.1056/NEJMoa2200075"}],"tags":[],"related":[],"cancers":["breast-hr-positive"],"sections":[],"technologies":["mrd-testing","endocrine-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["late-recurrence","mrd"],"trials":["soft-text","monarche"],"people":[],"bottlenecks":["b-dormancy-mrd","b-toxicity-qol","b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Stopping endocrine therapy at five years in serially MRD-negative patients gives non-inferior distant recurrence-free survival at ten years, with materially better quality of life.","rationale":"Late recurrence in hormone-receptor-positive breast cancer arises from long-lived dormant cells, exactly the population a sensitive assay should detect. De-escalation guided by a negative test has already been accepted in principle for chemotherapy through genomic assays, so the regulatory and clinical logic is familiar.","test":"A registry-based non-inferiority randomisation at year five, with annual genome-wide MRD testing, patient-reported outcomes as co-primary, and pre-specified rescue for those who convert to positive.","maturity":"speculative","actor":"clinic","cost":"medium","horizonYears":7},{"id":"idea-bio1-slfn11-payload-guidance","kind":"idea","name":"Use SLFN11 status to decide which antibody-drug payload to give next","aka":[],"tldr":"A single protein predicts whether a tumour will respond to DNA-damaging drug payloads. Measuring it could stop patients receiving a second drug of the same kind that will not work.","summary":"SLFN11 expression predicts sensitivity to topoisomerase 1 inhibitors and platinum across preclinical models and some clinical series, and its loss is a recognised mechanism of payload resistance. With most current ADCs carrying topoisomerase 1 payloads, SLFN11 immunohistochemistry on a progression biopsy could distinguish antigen-driven from payload-driven failure and direct patients to a different payload class such as a tubulin inhibitor.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Acquired resistance to every therapy): Soria et al., Osimertinib in untreated EGFR-mutated NSCLC (FLAURA, NEJM 2018)","url":"https://doi.org/10.1056/NEJMoa1713137"}],"tags":[],"related":["idea-payload-switching","idea-her2-adc-sequencing-payload"],"cancers":[],"sections":[],"technologies":["adc","histopathology-ihc","topoisomerase-inhibitors"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["payload","adc-sequencing"],"trials":[],"people":[],"bottlenecks":["b-resistance","b-biomarker-validation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"SLFN11 loss at progression identifies payload-class resistance and predicts failure of a second topoisomerase-payload ADC, while SLFN11-retained tumours can benefit from an antigen switch within the same payload class.","rationale":"SLFN11 status provides the missing test that turns payload-class switching from a rule of thumb into a biomarker-directed decision; the assay is a standard immunohistochemistry stain.","test":"Retrospective SLFN11 staining of progression biopsies from patients who received sequential ADCs, correlating with response to the second agent; prospective validation in a sequencing trial.","maturity":"preclinical-evidence","actor":"research","cost":"small","horizonYears":3},{"id":"idea-bio2-transferrin-shuttle-adc","kind":"idea","name":"Use the brain's own transport door to carry antibody drugs across","aka":[],"tldr":"The brain imports iron through the transferrin receptor. Antibody shuttle domains that bind that receptor raise brain exposure roughly ten to fifty-fold in primates and are already used in clinical Alzheimer's antibodies; the same engineering could carry antibody-drug conjugates or T-cell engagers to brain metastases.","summary":"Transferrin receptor-binding shuttle domains raise brain exposure of antibodies roughly ten to fifty-fold in primates and are being used in clinical Alzheimer's antibodies and enzyme replacement therapies. Applying the same engineering to antibody-drug conjugates or T-cell engagers directed at brain metastasis antigens is a well-defined, if demanding, protein engineering task with a real precedent from another disease area.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The brain: barrier and sanctuary): Stupp et al., Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma (NEJM 2005)","url":"https://doi.org/10.1056/NEJMoa043330"}],"tags":[],"related":[],"cancers":["breast-her2-positive","nsclc"],"sections":[],"technologies":["adc","bispecific-antibody","t-cell-engager"],"targets":["her2","her3","trop2"],"drugs":["trastuzumab-deruxtecan","tucatinib"],"companies":[],"institutions":[],"pathways":[],"terms":["blood-brain-barrier","her2-brain-metastases"],"trials":[],"people":[],"bottlenecks":["b-brain-delivery","b-undruggable-targets"],"keyPapers":["paper-slamon-her2-breast-ovarian-science-1989","paper-yarden-sliwkowski-erbb-network-nrmcb-2001"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A shuttle-enabled HER2 antibody-drug conjugate achieves at least tenfold higher brain concentration than the parent molecule and produces intracranial responses in patients whose brain metastases progress on standard ADCs.","rationale":"Shuttle engineering has moved from concept to clinical validation in neurology, so the platform risk is now largely retired. Brain metastases with retained antigen expression are a large, poorly served population where the only obstacle is delivery.","test":"Measure primate brain pharmacokinetics of shuttle versus parent conjugate, then run a phase 1 in HER2-positive brain metastasis with intracranial response and, where feasible, cerebrospinal fluid or resected-tissue drug measurement.","maturity":"preclinical-evidence","actor":"industry","cost":"medium","horizonYears":8},{"id":"idea-prev-blood-count-trend-flags","kind":"idea","name":"Use the trend in routine blood counts, not a single threshold, to spot cancer","aka":[],"tldr":"A platelet count that is normal but rising year on year, or haemoglobin drifting down, can signal cancer. Records already hold these trends; software could use them.","summary":"Thrombocytosis and unexplained anaemia are known predictors; longitudinal within-person trends are more informative than population thresholds. Propose trend-based alerting in primary care (e.g. a 20% platelet rise over two years within the normal range), evaluated in a linked-data cohort and then an RCT.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The hardest cancers are found late): Crosby et al., Early detection of cancer (Science 2022)","url":"https://doi.org/10.1126/science.aay9040"}],"tags":[],"related":[],"cancers":[],"sections":["early-detection","diagnostics"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-early-detection"],"keyPapers":["paper-crosby-science"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Within-person trend flags identify at least 20% more incident cancers 6-12 months before diagnosis than threshold-based flags at the same alert rate.","rationale":"Analogous to using individual baselines rather than population cut-offs in other fields; the data is already collected.","test":"Retrospective validation in CPRD or similar linked datasets (small cost); then a prospective pragmatic trial.","maturity":"speculative","actor":"data","cost":"small","horizonYears":3},{"id":"idea-tr1-ctdna-guided-stop-in-metastatic-disease","kind":"idea","name":"Use tumour DNA in blood to decide when to pause treatment in metastatic cancer","aka":[],"tldr":"If a blood test shows no tumour DNA after months of treatment, a trial could test pausing the drug and restarting only when the DNA reappears, giving patients time off without waiting for scans to show growth.","summary":"Randomised trials in metastatic disease where patients with sustained ctDNA clearance on therapy are allocated to continued treatment or a monitored treatment holiday with ctDNA-triggered resumption. Endpoints: time to treatment failure, time on treatment, QoL, OS non-inferiority. Distinct from adjuvant ctDNA-guided escalation (DYNAMIC, IMvigor011), this addresses de-escalation in the palliative setting where lead time over imaging gives a safety margin.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Trial design, endpoints and cost): Davis et al., Availability of evidence of benefits on survival and quality of life of cancer drugs approved by EMA 2009-13 (BMJ 2017)","url":"https://doi.org/10.1136/bmj.j4530"}],"tags":[],"related":[],"cancers":["colorectal","nsclc"],"sections":[],"technologies":["liquid-biopsy","mrd-testing"],"targets":[],"drugs":[],"companies":["natera","guardant-health"],"institutions":[],"pathways":[],"terms":["ctdna"],"trials":["dynamic","imvigor011"],"people":[],"bottlenecks":["b-trial-design","b-toxicity-qol"],"keyPapers":["paper-davis-bmj"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"ctDNA-guided holidays in responders will reduce time on drug by at least a third with non-inferior OS and better QoL, and molecular relapse will be detected before clinical deterioration in the large majority.","rationale":"ctDNA falls precede radiographic response and molecular relapse precedes radiographic progression by months in several tumour types. Intermittent strategies in colorectal cancer (chemotherapy holidays) were safe when guided by clinical criteria alone.","test":"Run a phase 2/3 trial in a ctDNA-shedding cancer (colorectal or lung) randomising sustained-clearance patients to holiday vs continuation, with pre-specified non-inferiority on OS at two years.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":4},{"id":"idea-bio1-resistance-mutation-vaccine","kind":"idea","name":"Vaccinate against the resistance mutation before it takes over","aka":[],"tldr":"Resistance often arrives as the same few mutations. Teaching the immune system to recognise them in advance could remove the escaping cells while they are still rare.","summary":"Recurrent resistance alleles such as EGFR T790M, ESR1 hotspot mutations and KRAS secondary mutations create new peptides, absent from normal cells, that may be presented on MHC. An off-the-shelf vaccine or T-cell product against a small set of public resistance neoantigens, given at the start of or during targeted therapy, would apply immune pressure precisely to the cells that are expanding under drug pressure.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Acquired resistance to every therapy): Soria et al., Osimertinib in untreated EGFR-mutated NSCLC (FLAURA, NEJM 2018)","url":"https://doi.org/10.1056/NEJMoa1713137"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["shared-antigen-vaccine","neoantigen-mrna-vaccine"],"targets":["egfr","estrogen-receptor"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["neoantigen","resistance"],"trials":[],"people":[],"bottlenecks":["b-resistance","b-immunotherapy-response"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Vaccination against a recurrent resistance neoantigen generates detectable specific T cells and reduces the emergence of that allele in plasma during targeted therapy.","rationale":"Public resistance mutations are shared across many patients, which makes an off-the-shelf product feasible; targeting a clone while it is rare is when immune clearance is most plausible.","test":"Immunogenicity and pharmacodynamic study in patients on osimertinib or an oral SERD, comparing allele emergence rates in plasma between vaccinated and control groups.","maturity":"speculative","actor":"research","cost":"medium","horizonYears":7},{"id":"idea-bio1-clonal-neoantigen-vaccines","kind":"idea","name":"Vaccines aimed only at mutations shared by every tumour cell","aka":[],"tldr":"Personal cancer vaccines target a list of mutations, some present in only part of the tumour, so the tumour can escape by losing them. Restricting vaccines and T-cell products to clonal mutations shared by every tumour cell, identified by multi-region sequencing, should close that escape route.","summary":"Clonal (truncal) neoantigens are present in all tumour cells, so an immune response to them cannot be escaped by subclonal antigen loss. Multi-region sequencing or high-purity clonality inference can identify them. Personalised mRNA vaccines and clonal-neoantigen-reactive T-cell products (such as those pioneered from TRACERx data) could be restricted to clonal targets and compared with unselected designs.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Tumour heterogeneity and clonal evolution): Gerlinger et al., Intratumor heterogeneity and branched evolution (NEJM 2012)","url":"https://doi.org/10.1056/NEJMoa1113205"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["neoantigen-mrna-vaccine","til-therapy"],"targets":[],"drugs":[],"companies":["moderna","biontech"],"institutions":[],"pathways":[],"terms":["neoantigen"],"trials":["interpath-001"],"people":[],"bottlenecks":["b-tumor-heterogeneity","b-immunotherapy-response"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Vaccines or T-cell products restricted to clonal neoantigens produce fewer antigen-loss relapses and longer disease-free survival than products built from unselected neoantigen lists of equal size.","rationale":"Clonal neoantigen burden, not total burden, predicted checkpoint inhibitor response in lung and melanoma cohorts; escape by loss of subclonal antigens is a documented failure mode.","test":"Randomised phase 2 in the adjuvant setting comparing clonal-restricted versus standard neoantigen selection with the same vaccine platform; endpoint recurrence-free survival and antigen-loss at relapse.","maturity":"early-clinical","actor":"industry","cost":"large","horizonYears":5},{"id":"idea-fund-rt-planning-ai-capacity","kind":"idea","name":"Validate and reimburse AI contouring and planning to expand radiotherapy capacity","aka":[],"tldr":"Drawing targets and planning radiotherapy takes hours of scarce expert time. Properly tested AI could do much of it, letting the same staff treat far more patients, if regulators and payers set clear rules for proving and paying for it.","summary":"A programme with three parts: prospective, multi-centre validation studies of auto-contouring and auto-planning against expert consensus with clinical-acceptability and time-saved endpoints; a regulatory pathway that accepts these endpoints for clearance; and payer recognition that shifts payment from planning time to plan quality, so that time saved translates into more patients treated rather than lost revenue. Radiotherapy workforce shortages (physicists, dosimetrists, radiation oncologists) limit capacity in rich and poor countries alike, and AI planning is the most mature clinical AI in oncology, yet its adoption is slowed by unclear evidence standards and payment rules.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Surgery and radiotherapy cure most, get least): Sullivan et al., Global cancer surgery (Lancet Oncology Commission 2015)","url":"https://doi.org/10.1016/S1470-2045(15)00223-5"}],"tags":[],"related":["idea-fund-radiotherapy-trials-infrastructure","idea-fund-lmic-radiotherapy-finance"],"cancers":[],"sections":[],"technologies":["imrt-igrt","radiology-ai-screening"],"targets":[],"drugs":[],"companies":["varian","elekta","siemens-healthineers"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-surgery-radiation-innovation","b-workforce","b-ai-validation"],"keyPapers":["paper-sullivan-lancet-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Validated AI contouring and planning reduces planning time per patient by more than half without loss of plan quality in prospective multi-centre studies, and departments adopting it under supportive payment rules increase patients treated per staff member by at least a fifth within two years.","rationale":"Randomised and prospective studies of auto-contouring already show large time savings with acceptable quality for several sites; the barrier is systemic. Radiotherapy is the one area where AI could directly relieve a workforce constraint that rations curative treatment.","test":"Run a prospective multi-centre validation with time and quality endpoints, then a stepped-wedge implementation across ten departments measuring throughput and staff time.","maturity":"being-tested-at-scale","actor":"regulator","cost":"medium","horizonYears":3},{"id":"idea-reg-metronomic-lmic-phase3-to-label","kind":"idea","name":"Validate low-cost metronomic oral regimens in phase 3 and carry them into guidelines","aka":[],"tldr":"Indian trials have shown that tiny daily doses of old oral chemotherapy drugs can help patients with head and neck cancer at a cost of a few dollars a month. These regimens should be proven and adopted worldwide.","summary":"Tata Memorial Centre's randomised trials of low-dose oral metronomic chemotherapy (methotrexate plus celecoxib, later triple metronomic therapy) in head and neck cancer reported survival comparable or superior to intravenous cisplatin in palliative settings at a fraction of the cost, and low-dose nivolumab added to metronomic therapy improved survival in another trial. These results have had limited uptake outside India. The proposal is a coordinated programme of confirmatory phase 3 trials in several LMICs across common cancers (head and neck, cervical, breast), with an explicit path to WHO essential medicines listing and guideline inclusion.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (No incentive to repurpose cheap drugs): Pantziarka et al., The Repurposing Drugs in Oncology (ReDO) Project (ecancer 2014)","url":"https://doi.org/10.3332/ecancer.2014.442"}],"tags":[],"related":[],"cancers":["head-and-neck","cervical"],"sections":[],"technologies":["cytotoxic-chemotherapy"],"targets":[],"drugs":[],"companies":[],"institutions":["tata-memorial"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-generic-repurposing","b-global-access"],"keyPapers":["paper-pantziarka-ecancermedicalscience"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Metronomic regimens confirmed in multinational phase 3 trials are non-inferior in overall survival to standard intravenous regimens in defined palliative settings at less than a tenth of the drug cost, and are adopted into WHO and national guidelines within two years of publication.","rationale":"The Indian trials are the most cost-effective oncology results of the past decade and were possible only because a public institution ran them; replication is the step that will make them global practice.","test":"Fund two multinational phase 3 trials in head and neck and cervical cancer across five LMICs with OS primary endpoints and cost-effectiveness analyses, with WHO involvement from the outset.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":5},{"id":"idea-data-rwpfs-validation-programme","kind":"idea","name":"Validate real-world progression against central imaging review","aka":[],"tldr":"Real-world studies say a drug 'stopped working' based on clinic notes. Check how often that matches a proper scan review, and fix the definitions so the two agree.","summary":"Real-world PFS (rwPFS) and real-world response are derived from clinician notes and imaging reports, with definitions that differ by vendor. Concordance with RECIST-based central review is only moderately studied. The proposal is a programme in which a sample of real-world progression events in federated datasets is re-read by blinded central radiology, error rates are published by cancer type and data source, and a harmonised definition with known operating characteristics is adopted by regulators.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Weak real-world evidence and registries): Gyawali, Hey & Kesselheim, Assessment of the clinical benefit of cancer drugs receiving accelerated approval (JAMA Intern Med 2019)","url":"https://doi.org/10.1001/jamainternmed.2019.0462"}],"tags":[],"related":[],"cancers":[],"sections":["ai-computation","imaging"],"technologies":[],"targets":[],"drugs":[],"companies":["tempus"],"institutions":[],"pathways":[],"terms":["pfs","recist","real-world-evidence"],"trials":[],"people":[],"bottlenecks":["b-real-world-evidence"],"keyPapers":["paper-gyawali-jama-intern-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Harmonised, validated rwPFS definitions will show agreement with RECIST-based progression within one month in more than 80 percent of events for solid tumours and will be accepted as a supportive endpoint in regulatory submissions.","rationale":"Endpoint validity is the main reason regulators discount RWE for effectiveness; a one-time validation programme is far cheaper than the trials RWE is meant to supplement.","test":"Re-read 1,500 real-world progression events across three cancers with blinded RECIST review; publish sensitivity, specificity and timing bias by data source.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":2},{"id":"idea-tr1-validate-real-world-progression-endpoints","kind":"idea","name":"Validate real-world progression endpoints so pragmatic trials can use them","aka":[],"tldr":"Pragmatic trials want to use the progression dates recorded in ordinary clinic notes instead of expensive protocol scans. Checking how well those routine records match formal trial measurements would show when that shortcut is safe.","summary":"Paired studies in which patients enrolled in conventional trials also have their routine clinical progression (rwPFS from clinician notes and imaging reports, abstracted or NLP-derived) captured, quantifying agreement in progression dates and hazard ratios by tumour type. Regulators publish acceptable-use conditions for rwPFS and time-to-next-treatment as endpoints in pragmatic and registry-based trials.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Trial design, endpoints and cost): Davis et al., Availability of evidence of benefits on survival and quality of life of cancer drugs approved by EMA 2009-13 (BMJ 2017)","url":"https://doi.org/10.1136/bmj.j4530"}],"tags":[],"related":["genie"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["pfs","recist","real-world-evidence"],"trials":[],"people":[],"bottlenecks":["b-trial-design","b-real-world-evidence","b-biomarker-validation"],"keyPapers":["paper-davis-bmj"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"In common solid tumours, rwPFS will yield hazard ratios within a pre-specified tolerance of RECIST-based PFS, enabling pragmatic trials to drop protocol imaging schedules in those settings.","rationale":"Retrospective comparisons of rwPFS and trial PFS show reasonable agreement in some cancers; prospective paired validation would allow protocol-free endpoints and make registry-embedded and pragmatic trials far cheaper.","test":"Embed routine-record endpoint capture in three ongoing phase 3 trials and report concordance of progression dates and hazard ratios.","maturity":"early-clinical","actor":"data","cost":"medium","horizonYears":3},{"id":"idea-tr2-ai-cdx-change-control","kind":"idea","name":"Version control and locked reference sets for AI algorithms used as companion diagnostics","aka":[],"tldr":"AI is starting to decide which patients get which cancer drug. Every change to the software should be tested against a fixed public set of cases before it is used on patients.","summary":"AI-based scoring of HER2, PD-L1 and other markers is entering clinical use. Software updates can shift positivity rates silently. Regulators (FDA's predetermined change control plans, EU AI Act) are building frameworks. A concrete requirement for oncology companion diagnostic algorithms: every version must report performance on a locked public reference set, changes must be logged with effect on positivity rates, and laboratories must record the algorithm version in each patient report.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Biomarkers are not validated or standardised): Fernandez et al., Examination of low ERBB2 protein expression in breast cancer tissue (JAMA Oncology 2022)","url":"https://doi.org/10.1001/jamaoncol.2021.7239"}],"tags":[],"related":["paige","pathai","idea-ai-her2-low-scoring","idea-tr2-open-cdx-validation-sets"],"cancers":[],"sections":[],"technologies":["digital-pathology-ai","pathology-foundation-model"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-biomarker-validation","b-ai-validation"],"keyPapers":["paper-fernandez-jama-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Version reporting will reveal at least one clinically meaningful drift (positivity change above five percentage points) in a deployed algorithm within two years, which would otherwise have gone undetected.","rationale":"Software versioning is routine in engineering and absent in diagnostic pathology reporting; drift has been documented in deployed medical AI.","test":"Implement version logging and reference-set testing for two deployed pathology algorithms across ten laboratories; monitor positivity rates by version.","maturity":"early-clinical","actor":"regulator","cost":"small","horizonYears":2},{"id":"idea-acc-tele-palliative-care-default","kind":"idea","name":"Video palliative care as an equivalent default option for patients far from a team","aka":[],"tldr":"A large trial showed that palliative care delivered by video works as well as in person for people with advanced lung cancer. Payers should cover it so that distance from a hospital no longer decides who gets it.","summary":"The REACH PC trial (Greer and colleagues, reported 2024) found that early palliative care delivered by video was equivalent to in-person care on quality of life in advanced non-small-cell lung cancer. Most palliative care teams are in cities; most patients are not. Making video delivery a reimbursed, guideline-endorsed default, with in-person visits when needed, would extend the reach of a scarce workforce.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Pain relief and palliative care are unavailable to most): WHO fact sheet, Palliative care","url":"https://www.who.int/news-room/fact-sheets/detail/palliative-care"}],"tags":[],"related":[],"cancers":["nsclc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-palliative","b-workforce"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Regions covering tele-palliative care will increase the proportion of rural patients with advanced cancer receiving specialist palliative care within eight weeks of diagnosis by at least 25 percentage points.","rationale":"Equivalence has been shown in a large randomised trial; the constraint is payment policy and team workflow.","test":"A payer rollout with rural versus urban uptake, time to palliative contact, and end-of-life quality indicators as endpoints.","maturity":"being-tested-at-scale","actor":"payer","cost":"small","horizonYears":2},{"id":"idea-acc-return-to-work-rehabilitation","kind":"idea","name":"Vocational rehabilitation integrated into cancer care so survivors can return to work","aka":[],"tldr":"Cancer survivors are substantially more likely to be unemployed than the general population, though with support they could often work. Vocational rehabilitation covering fatigue management, cognitive strategies, employer liaison and phased return has moderate trial evidence, mostly from Europe, and should be part of cancer care from diagnosis with a named coordinator, as it is for stroke.","summary":"Cancer survivors are at substantially higher risk of unemployment than the general population, with large economic and psychological costs. Multidisciplinary vocational rehabilitation (fatigue management, cognitive strategies, employer liaison, phased return) has moderate evidence from trials, mostly in Europe, but is rarely funded within oncology. Integrating a return-to-work pathway from diagnosis, with a named coordinator, would address one of survivors' most reported unmet needs.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Survivorship and late effects are neglected): NCI Office of Cancer Survivorship statistics","url":"https://cancercontrol.cancer.gov/ocs/statistics"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Survivors offered integrated vocational rehabilitation will have return-to-work rates at 12 months at least 15 percentage points higher than usual care, with improved financial and quality-of-life outcomes.","rationale":"Return-to-work programmes are standard after stroke and cardiac events with demonstrated benefit; cancer survivors have similar functional barriers and a longer horizon of benefit.","test":"A randomised trial across four regions of working-age patients with employment status, income, and quality of life at 12 and 24 months as endpoints.","maturity":"early-clinical","actor":"payer","cost":"medium","horizonYears":3},{"id":"idea-cost-voluntary-licensing-oncology","kind":"idea","name":"Voluntary licences and price caps for patented cancer drugs in low-income countries","aka":[],"tldr":"India's 2012 compulsory licence on sorafenib cut its price by about 97% and its 2019 cap on trade margins lowered the shelf price of 42 cancer drugs; voluntary licences through a patent pool would achieve the same without a fight.","summary":"In 2012 India's Controller General of Patents granted Natco a compulsory licence to make sorafenib at a fraction of Bayer's price with a 6% royalty, the first for a cancer drug. In 2019 the National Pharmaceutical Pricing Authority capped trade margins on 42 non-scheduled anticancer drugs at 30%, cutting retail prices. The Medicines Patent Pool has since signed its first oncology licences. A standing voluntary-licensing route for essential cancer medicines, with tiered pricing agreed in advance, would give manufacturers certainty and low-income countries generic prices years before patent expiry.","asOf":"2026-09-10","links":[{"label":"Medicines Patent Pool","url":"https://medicinespatentpool.org/"},{"label":"National Pharmaceutical Pricing Authority (India) (archived copy)","url":"https://web.archive.org/web/20250708090325/http://www.nppaindia.nic.in/"},{"label":"Intellectual Property India","url":"https://ipindia.gov.in/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":["sorafenib","imatinib"],"companies":[],"institutions":["who","cdsco"],"pathways":[],"terms":["who-essential-medicines"],"trials":[],"people":[],"bottlenecks":["b-global-access","b-drug-pricing","b-ip-collaboration"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Voluntary licences for five patented essential cancer medicines will bring generic versions to at least 30 low- and middle-income countries within four years at prices below 10% of high-income list prices.","rationale":"The HIV precedent shows licensing plus generic competition, not charity, is what made treatment affordable at scale.","test":"Medicines Patent Pool reports licences signed, countries covered, generic launches and prices for oncology products.","maturity":"early-clinical","actor":"industry","cost":"medium","horizonYears":4},{"id":"idea-acc-neighbourhood-palliative-networks","kind":"idea","name":"Volunteer-led neighbourhood palliative networks, the Kerala model, adapted elsewhere","aka":[],"tldr":"In Kerala, trained community volunteers, backed by nurses and doctors, provide most home palliative care to the dying. The model reaches more people at lower cost than any clinic-based service and could be copied.","summary":"The Neighbourhood Network in Palliative Care in Kerala trains community volunteers to identify patients, provide social and basic nursing support, and link to professional teams, with local government funding and a state palliative care policy. Coverage is far higher than elsewhere in India. Adapting this community-owned model in other states and countries requires local ownership, a light professional backbone, and reliable morphine supply rather than large budgets.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Pain relief and palliative care are unavailable to most): WHO fact sheet, Palliative care","url":"https://www.who.int/news-room/fact-sheets/detail/palliative-care"}],"tags":[],"related":["idea-acc-community-health-workers-oncology"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-palliative","b-global-access","b-workforce"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Districts adopting a neighbourhood network model will achieve palliative care coverage of at least 50% of people dying with cancer within four years, compared with under 10% for clinic-based services.","rationale":"Community mobilisation delivered coverage in Kerala where health-system approaches did not; the ingredients are documented and transferable.","test":"Implementation in ten districts across three countries with coverage, home-death rates where preferred, and caregiver-reported quality of dying as endpoints.","maturity":"being-tested-at-scale","actor":"patients","cost":"small","horizonYears":3},{"id":"idea-prostate-plasticity-surveillance-before-it-is-neuroendocrine","kind":"idea","name":"Watch for the cancer changing cell type before the biopsy says neuroendocrine, and act on it","aka":["lineage plasticity surveillance prostate","TP53 RB1 loss monitoring prostate","pre-emptive platinum neuroendocrine prostate"],"tldr":"In a minority of men, prostate cancer escapes hormone drugs by becoming a different kind of cell that no longer needs the androgen receptor. By the time a biopsy shows it, the treatment options are almost gone. The genetic changes that allow the switch are detectable years earlier, and nobody is looking for them.","summary":"Mu and Ku showed in 2017 that combined loss of TP53 and RB1 function enables prostate cancer cells to shift from androgen receptor-dependent luminal cells to androgen receptor-independent basal-like cells, mediated by SOX2, and that restoring the tumour suppressors reverses it in the laboratory. Beltran had already shown that neuroendocrine prostate cancer arises by divergent clonal evolution from the same tumour rather than as a separate disease. Aggarwal found treatment-emergent small-cell neuroendocrine carcinoma in 17 percent of metastatic biopsies in a prospective cohort. Chung found RB1 alteration enriched in metastatic over primary samples.\n\nThe enabling lesions are therefore known, detectable in circulating tumour DNA, and present before the phenotype changes. What is missing is any protocol that uses them. A man with combined TP53 and RB1 loss who is started on a third androgen receptor-directed line is being given a treatment his tumour is predisposed to escape by the one route that leads nowhere. The proposal is a two-part programme: serial circulating tumour DNA genotyping for TP53 and RB1 status, plus a plasma transcriptional readout of neuroendocrine identity, in men starting an androgen receptor pathway inhibitor for castration-resistant disease; and a randomised test of whether men who convert should switch to platinum-based chemotherapy or a neuroendocrine-directed agent at conversion rather than at biopsy-proven transformation.\n\nWhat any of this means for someone treated in Britain, from the screening committee's position and the NICE appraisals to scanner and radiotherapy capacity, waiting times and how to reach a trial, is on the UK and NHS pathway page for prostate cancer.","asOf":"2026-09-25","links":[],"tags":["prostate-evidence"],"related":["idea-bio1-cfrna-plasticity-tracking","idea-bio1-ctc-derived-explants","prostate-roadmap","ctdna-tests"],"cancers":["prostate","prostate-mcrpc","prostate-nepc"],"sections":["diagnostics","targeted-therapy","chemotherapy"],"technologies":["liquid-biopsy","ngs"],"targets":["tp53","rb1","androgen-receptor"],"drugs":["carboplatin","cisplatin","enzalutamide","abiraterone"],"companies":[],"institutions":[],"pathways":[],"terms":["ctdna","castration-resistance","neuroendocrine-differentiation"],"trials":[],"people":[],"bottlenecks":["b-resistance","b-tumor-heterogeneity","b-rare-cancers","b-biomarker-validation","b-undruggable-targets"],"keyPapers":["paper-mu-sox2-lineage-plasticity-science-2017","paper-ku-rb1-trp53-lineage-plasticity-science-2017","paper-beltran-nepc-divergent-evolution-nat-med-2016","paper-aggarwal-t-sccpc-jco-2018","paper-rubin-mol-cell","paper-chung-comprehensive-genomic-profiling-prostate-jco-po-2019"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"In men with castration-resistant prostate cancer, combined TP53 and RB1 loss detected in circulating tumour DNA identifies, months before any histological change, the group in whom further androgen receptor-directed therapy will fail quickly, and switching that group to platinum-based or lineage-directed treatment at the point of molecular conversion rather than at biopsy-proven neuroendocrine transformation improves overall survival.","rationale":"The mechanism is established in models and the frequency is established in patients: 17 percent of metastatic biopsies in Aggarwal's cohort were treatment-emergent small-cell neuroendocrine carcinoma, a diagnosis with a median survival measured in months and no approved treatment. The enabling genotype is measurable without a biopsy. And the current pathway, which waits for a clinical suspicion strong enough to justify re-biopsying a man with bone-predominant disease, guarantees that the diagnosis is made late: the trigger for suspicion is usually visceral metastasis or a rising tumour burden with a flat prostate-specific antigen, both of which are late events. Every element of the test exists; none of them is sequenced together prospectively.","test":"A prospective cohort with an embedded randomisation. Enrol men starting an androgen receptor pathway inhibitor for castration-resistant disease; collect plasma at baseline and at each cycle for targeted circulating tumour DNA sequencing of TP53, RB1 and PTEN and for a neuroendocrine transcriptional signature; biopsy at progression where safe to establish the histological reference. The observational phase measures how far in advance molecular conversion precedes histological transformation and its positive predictive value. Men who convert are then randomised to immediate platinum-based chemotherapy against continued standard sequencing with treatment change at histological transformation, with overall survival as the primary endpoint. Four years to the lead-time answer, seven to the randomised one.","maturity":"preclinical-evidence","actor":"research","cost":"large","horizonYears":7},{"id":"idea-tr2-antagonism-surveillance","kind":"idea","name":"Watch routine care for drug combinations that quietly make cancer treatment worse","aka":[],"tldr":"Some everyday medicines, such as antibiotics or steroids, seem to blunt immunotherapy. Automatically scanning health records for such harmful pairs would catch them years earlier.","summary":"Antibiotics, proton-pump inhibitors and corticosteroids are associated with worse outcomes on checkpoint inhibitors in retrospective series, yet these signals took years to surface. A pharmacovigilance-style system that continuously screens clinico-genomic databases for concomitant medications associated with reduced efficacy (not just toxicity) would generate hypotheses for confirmation and, where confirmed, guideline warnings.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Too many combinations to test): Palmer & Sorger, Combination cancer therapy can confer benefit via patient-to-patient variability without drug additivity or synergy (Cell 2017)","url":"https://doi.org/10.1016/j.cell.2017.11.009"}],"tags":[],"related":["tempus"],"cancers":[],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":[],"drugs":["pembrolizumab","nivolumab"],"companies":[],"institutions":[],"pathways":[],"terms":["real-world-evidence"],"trials":[],"people":[],"bottlenecks":["b-combination-space","b-real-world-evidence"],"keyPapers":["paper-palmer-cell"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Systematic surveillance will identify at least three previously unrecognised efficacy-reducing co-medications for immunotherapy or targeted therapy within two years, at least one of which is confirmed in a randomised or well-controlled study.","rationale":"Adverse-event pharmacovigilance is mature; efficacy pharmacovigilance is not, even though negative interactions on survival matter more than most side-effects.","test":"Run signal detection across a large clinico-genomic database for patients on PD-1 inhibitors; validate top signals in an independent registry; publish a ranked list.","maturity":"early-clinical","actor":"data","cost":"small","horizonYears":2},{"id":"idea-prev-small-renal-mass-surveillance","kind":"idea","name":"Watch small kidney tumours rather than remove them, with a national registry","aka":[],"tldr":"Most kidney tumours under 3 cm found by chance grow under 0.3 cm a year, rarely spread, and a fifth are benign. Surveillance with a biopsy for grade as the default in patients over 65, with a national registry and set triggers for surgery, could spare most of these operations.","summary":"The DISSRM registry and Canadian cohorts show growth under 0.3 cm per year and rare metastasis for small renal masses under surveillance. Propose surveillance with renal mass biopsy for grade as the default for masses under 3 cm in patients over 65, with a national registry and explicit intervention triggers.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Overdiagnosis and false alarms): Welch & Black, Overdiagnosis in cancer (JNCI 2010)","url":"https://doi.org/10.1093/jnci/djq099"}],"tags":[],"related":[],"cancers":["rcc"],"sections":["early-detection"],"technologies":["ct"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-overdiagnosis","b-aging-comorbidity"],"keyPapers":["paper-welch-j-natl-cancer-inst"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Default surveillance cuts nephrectomy and ablation for small renal masses by at least half with a metastasis rate under 2% at five years.","rationale":"Existing cohorts support safety, and nephron preservation improves cardiovascular outcomes.","test":"Registry with pre-specified safety monitoring plus a randomised decision-support trial.","maturity":"early-clinical","actor":"clinic","cost":"small","horizonYears":4},{"id":"idea-bio2-tcr-repertoire-early-readout","kind":"idea","name":"Watch the immune system's response in the blood three weeks in","aka":[],"tldr":"When immunotherapy works, specific immune cell families multiply in the blood within weeks. Tracking that could tell patients early whether to continue.","summary":"Peripheral T-cell receptor repertoire dynamics (clonal expansion, clonal replacement and the appearance of tumour-matched clones) have been associated with response in melanoma, lung and bladder cancer, but the analyses are retrospective, use different metrics and different platforms, and have never been locked as a prospective decision rule. Sequencing cost is now low enough for serial monitoring.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (No one can predict who responds to immunotherapy): Haslam & Prasad (JAMA Network Open 2019)","url":"https://doi.org/10.1001/jamanetworkopen.2019.2535"}],"tags":[],"related":[],"cancers":["melanoma","nsclc","urothelial"],"sections":[],"technologies":["ngs-mrd-clonoseq","rna-seq","checkpoint-inhibitor","liquid-biopsy"],"targets":[],"drugs":[],"companies":["adaptive-biotechnologies"],"institutions":[],"pathways":[],"terms":["irae","orr"],"trials":[],"people":[],"bottlenecks":["b-immunotherapy-response","b-biomarker-validation"],"keyPapers":["paper-haslam-jama-netw-open"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A locked repertoire dynamics metric measured at baseline and three weeks identifies non-responders with negative predictive value above 85%, allowing early switch decisions before radiographic progression.","rationale":"Repertoire change is mechanistically upstream of tumour shrinkage, and blood is easy to sample serially. The same logic works clinically in leukaemia through clonality tracking, and the assays are already commercially available.","test":"Prospective locked-metric validation in an existing checkpoint inhibitor trial with serial blood samples, pre-registering the metric, threshold and analysis plan before unblinding.","maturity":"early-clinical","actor":"data","cost":"medium","horizonYears":4},{"id":"idea-data-wearable-endpoints-validation","kind":"idea","name":"Wearable activity data as a validated real-world endpoint","aka":[],"tldr":"Step counts and sleep from a wristband could show whether a cancer treatment is helping or harming daily life. Prove they track survival and quality of life, then use them in real-world studies.","summary":"Performance status is coarse and clinician-rated. Wearable-derived measures (daily steps, active minutes, sleep) have correlated with survival and hospitalisation in small oncology studies. The proposal is a large validation programme: wearables issued in routine care at several centres, linked to ePRO and registry outcomes, to establish which digital measures are prognostic, responsive to treatment effect and acceptable as regulatory endpoints in real-world and pragmatic studies.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Weak real-world evidence and registries): Gyawali, Hey & Kesselheim, Assessment of the clinical benefit of cancer drugs receiving accelerated approval (JAMA Intern Med 2019)","url":"https://doi.org/10.1001/jamainternmed.2019.0462"}],"tags":[],"related":[],"cancers":[],"sections":["ai-computation","supportive-care"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["real-world-evidence"],"trials":[],"people":[],"bottlenecks":["b-real-world-evidence","b-toxicity-qol"],"keyPapers":["paper-gyawali-jama-intern-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A validated digital activity endpoint will predict overall survival better than clinician-rated performance status and detect treatment-related functional decline weeks earlier.","rationale":"Gresham et al. and others found step counts predict hospitalisation and survival in advanced cancer; the endpoint lacks the scale of validation regulators require.","test":"Issue wearables to 3,000 patients starting systemic therapy across five centres; pre-register the analysis of steps versus survival and ePRO; seek qualification of the endpoint with regulators.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":3},{"id":"idea-acc-electronic-pro-monitoring-standard","kind":"idea","name":"Weekly electronic symptom reporting as a standard of care during systemic therapy","aka":[],"tldr":"Patients on chemotherapy who report their symptoms weekly through an app, with nurses acting on alerts, live longer and visit emergency rooms less. This should be routine and paid for.","summary":"Randomised trials (Basch and colleagues, 2016-2022) showed that routine electronic patient-reported outcome monitoring with nurse response improves quality of life, reduces emergency visits, and in one trial improved overall survival. Adoption remains patchy because of workflow and payment barriers. The proposal is to make PRO monitoring a reimbursed standard of care during systemic therapy, with minimum response standards and open symptom item sets.","asOf":"2026-09-08","links":[{"label":"Basch et al., JAMA 2017: overall survival with PRO monitoring","url":"https://jamanetwork.com/journals/jama/fullarticle/2630810"}],"tags":[],"related":[],"cancers":[],"sections":["supportive-care"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-care-fragmentation","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Systems that adopt reimbursed PRO monitoring will reduce emergency attendance during chemotherapy by at least 10% and improve symptom control scores, replicating trial effects at population scale.","rationale":"The effect is one of the largest supportive-care benefits with Level 1 evidence; the barrier is implementation, which payment and standards can address.","test":"A payer-led rollout across multiple practices with matched-control comparison of emergency visits, hospitalisations, and patient-reported symptom burden.","maturity":"being-tested-at-scale","actor":"payer","cost":"medium","horizonYears":2},{"id":"idea-moon-pro-monitoring-standard","kind":"idea","name":"Weekly symptom check-ins with automatic alerts as standard of care on treatment","aka":[],"tldr":"Patients on chemotherapy or immunotherapy answer a short weekly symptom questionnaire on their phone; severe answers alert the nurse the same day. Trials show this prolongs life.","summary":"Electronic patient-reported outcome monitoring with nurse alerts improved quality of life, reduced emergency visits and improved overall survival in a randomised trial at Memorial Sloan Kettering (Basch et al.) and in the PRO-TECT cluster-randomised trial in community practices. Uptake remains low because nobody is paid for the nursing time. The proposal is a reimbursed care standard: every patient on active systemic therapy is offered weekly ePRO monitoring with defined alert thresholds and response times, and payers cover the monitoring as they cover a drug.","asOf":"2026-09-08","links":[{"label":"NCI PRO-CTCAE","url":"https://healthcaredelivery.cancer.gov/pro-ctcae/"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["mskcc"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-patient-voice","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"System-wide ePRO monitoring reduces unplanned admissions during systemic therapy by at least 15% and improves symptom control, and the savings exceed the cost of nursing time.","rationale":"Clinicians under-detect symptoms between visits; early management of dehydration, pain and nausea prevents cascades to admission. The evidence base is unusual in supportive care for including a survival signal.","test":"Payer-led pragmatic rollout with a randomised stepped start across practices; measure admissions, emergency visits, dose intensity delivered and patient-reported symptom burden.","maturity":"being-tested-at-scale","actor":"payer","cost":"medium","horizonYears":3},{"id":"idea-immune-exclusion-drivers","kind":"idea","name":"What actually holds T cells at the tumour border?","aka":[],"tldr":"In immune-excluded tumours T cells reach the border but cannot get in, held back by fibroblasts, matrix, abnormal vessels, CXCL12 gradients or myeloid cells, and TGF-β drugs on their own have failed. If single-cell and spatial profiling can show which stromal programme dominates in each tumour, matching the drug (TGF-β, FAP, CXCR4 or VEGF) to it could let immunotherapy work.","summary":"This open question asks what actually holds T cells at the tumour border: in immune-excluded tumours the immune cells are present but cannot get in, and knowing the dominant barrier would open the gate. Fibroblasts, matrix, abnormal vessels, CXCL12 gradients and myeloid cells are all implicated, yet TGF-β-directed drugs failed as monotherapy, suggesting redundancy or wrong patient selection. The hypothesis is that a few stromal programmes, classifiable by Single-cell & spatial profiling, drive Immune exclusion, so matching the agent (TGF-β, FAP, CXCR4 or VEGF) to the programme converts excluded tumours into inflamed ones. The test is a biomarker-stratified window trial with PD-1 blockade, and the idea links to FAPI PET and Hot vs cold tumours.","asOf":"2026-09-08","links":[{"label":"Mariathasan et al., TGF-beta attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells (Nature 2018)","url":"https://doi.org/10.1038/nature25501"}],"tags":["mechanism","open-question"],"related":[],"cancers":[],"sections":[],"technologies":["single-cell-spatial","fapi-pet","checkpoint-inhibitor"],"targets":["fap","vegf","pd1"],"drugs":[],"companies":[],"institutions":["gustave-roussy","mskcc","institut-curie"],"pathways":["tumor-microenvironment","tgf-beta","pd1-checkpoint"],"terms":["immune-exclusion","cold-vs-hot"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-mariathasan-nature"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Immune exclusion is driven by a small number of stromal programmes that can be classified from spatial profiling, and matching the anti-stromal agent to the programme (TGF-β vs FAP vs CXCR4 vs VEGF) converts excluded tumours to inflamed ones.","rationale":"Mariathasan 2018 and Tauriello 2018 showed TGF-β causality in models; spatial atlases show distinct exclusion architectures; FAP theranostics and CXCR4 antagonists reach the clinic.","test":"Biomarker-stratified window-of-opportunity trial: spatial transcriptomic classification of excluded tumours, randomise to matched stromal agent plus PD-1 versus PD-1 alone, primary endpoint change in intratumoural CD8 density.","maturity":"early-clinical"},{"id":"idea-dtc-colonisation-determinants","kind":"idea","name":"What decides which disseminated cells ever colonise?","aka":[],"tldr":"Most cancer cells that spread die or sleep forever; a few grow into lethal metastases. Nobody can yet tell them apart, and doing so would show whom to treat after surgery.","summary":"This open question asks what decides which disseminated cancer cells ever colonise: most die or sleep forever, a few grow into lethal metastases, and nobody can yet tell them apart. Bone marrow Disseminated tumour cells (DTCs) are common yet Late recurrence is uncommon; candidates include stemness programmes, niche interactions, immune surveillance and stochastic awakening (see Tumour dormancy). The hypothesis is that a measurable DTC state at surgery predicts late metastasis independently of stage and could be targeted with dormancy-enforcing therapy. The test is single-cell DTC profiling plus serial ctDNA in stage II-III breast cancer, relevant to HR-positive / HER2-negative breast cancer, Triple-negative breast cancer (TNBC) and Prostate cancer.","asOf":"2026-09-08","links":[{"label":"Massague and Obenauf, Metastatic colonisation by circulating tumour cells (Nature 2016)","url":"https://doi.org/10.1038/nature17038"}],"tags":["mechanism","open-question"],"related":[],"cancers":["breast-hr-positive","tnbc","prostate"],"sections":[],"technologies":["mrd-testing","single-cell-spatial"],"targets":[],"drugs":[],"companies":[],"institutions":["mount-sinai","mskcc","cold-spring-harbor"],"pathways":["metastatic-cascade","tumor-dormancy"],"terms":["disseminated-tumor-cells","late-recurrence"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-massague-nature"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A measurable DTC state (e.g., NR2F1-low, proliferation-primed, immune-evasive) present at surgery predicts late metastasis independently of stage and could be targeted with dormancy-enforcing therapy.","rationale":"Aguirre-Ghiso's NR2F1 dormancy programme, MSK latency-competent cell work, and TRACERx show dissemination is early and heterogeneous; MRD assays now let DTC biology be followed clinically.","test":"Prospective cohort with bone marrow DTC single-cell profiling plus serial ctDNA in stage II-III breast cancer, correlating DTC state with 10-year distant recurrence; nested randomised dormancy-maintenance trial (5-azacytidine + ATRA) in DTC-positive patients.","maturity":"preclinical-evidence"},{"id":"idea-neoantigen-immunogenicity-rules","kind":"idea","name":"What makes a neoantigen actually immunogenic?","aka":[],"tldr":"Vaccines can now encode dozens of a tumour's mutations, but only a minority provoke useful T cells. Learning the rules would make vaccines smaller, cheaper, and stronger.","summary":"This open question asks what makes a neoantigen immunogenic: vaccines encode dozens of mutations but only a minority provoke useful T cells, and learning the rules would make vaccines smaller and stronger. Prediction relies on HLA binding and expression, but immunogenicity also depends on TCR repertoire, dissimilarity to self, clonality and dendritic cell presentation (Antigen presentation & immune editing pathway). Long-term responders in the Balachandran pancreatic cohort provide ground truth, and INTerpath-001 follow-up supplies immune-monitoring data. The hypothesis is that a model trained on T-cell responses from trials of Intismeran autogene and other Personalised neoantigen (mRNA) vaccines can cut epitopes per vaccine from 34 to under 10.","asOf":"2026-09-08","links":[{"label":"Wells et al., Key parameters of tumour epitope immunogenicity revealed through a consortium approach (Cell 2020)","url":"https://doi.org/10.1016/j.cell.2020.09.015"}],"tags":["mechanism","open-question"],"related":[],"cancers":[],"sections":[],"technologies":["neoantigen-mrna-vaccine","tcr-t"],"targets":[],"drugs":["intismeran-autogene","autogene-cevumeran"],"companies":[],"institutions":["mskcc","wustl-siteman","nci"],"pathways":["antigen-presentation-immunoediting"],"terms":["neoantigen"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-wells-cell"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Immunogenic neoantigens can be predicted with >50% precision by models trained on validated T-cell responses from vaccine trials, cutting the number of epitopes needed per vaccine from 34 to under 10.","rationale":"INTerpath-001 success and autogene cevumeran follow-up supply immune-monitoring data; TCR-sequencing and antigen-specific assays are scalable.","test":"Pooled analysis of vaccine-trial immunomonitoring to train and prospectively validate an immunogenicity model; then a randomised trial of model-selected 10-epitope vs standard 34-epitope vaccines with T-cell response as primary endpoint.","maturity":"preclinical-evidence"},{"id":"idea-bio2-localise-the-mrd","kind":"idea","name":"When the blood test is positive, hunt for the lesion with sensitive imaging","aka":[],"tldr":"A positive blood test tells you cancer is back but not where. Combining whole-body MRI with modern PET tracers may find a single spot that can be zapped.","summary":"Patients who are ctDNA-positive but scan-negative are currently given systemic therapy or nothing. Whole-body MRI plus a lineage-appropriate PET tracer (PSMA, somatostatin receptor, FAP or fibroblast-directed imaging) detects lesions well below conventional CT thresholds, which would allow ablative treatment of true oligorecurrence and spare the rest systemic therapy.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Dormant cells and minimal residual disease): Tie et al., ctDNA analysis guiding adjuvant therapy in stage II colon cancer (NEJM 2022)","url":"https://doi.org/10.1056/NEJMoa2200075"}],"tags":[],"related":["idea-psma-pet-guided-mdt"],"cancers":["colorectal","breast-hr-positive","prostate"],"sections":[],"technologies":["whole-body-mri","psma-pet","fapi-pet","sbrt","mrd-testing","sstr-pet"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["oligometastatic","biochemical-recurrence"],"trials":[],"people":[],"bottlenecks":["b-dormancy-mrd","b-metastasis-biology"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"In ctDNA-positive, CT-negative patients, whole-body MRI plus a targeted PET tracer localises disease in at least 40%, and ablation of all detected lesions clears ctDNA in half of those patients.","rationale":"PSMA PET already redefined biochemical recurrence in prostate cancer by finding lesions in patients previously classed as non-localisable, and metastasis-directed therapy in that setting delays systemic treatment.","test":"A prospective imaging cohort in ctDNA-positive colorectal and breast cancer measuring localisation rate; if the rate exceeds a pre-set threshold, proceed to a randomised trial of ablation plus systemic therapy versus systemic therapy alone.","maturity":"early-clinical","actor":"clinic","cost":"medium","horizonYears":4},{"id":"idea-chip-risk-modifiers","kind":"idea","name":"Which patients' blood clones will become leukaemia after treatment?","aka":[],"tldr":"PARP inhibitors, platinum, and radioligand drugs can push pre-existing blood-cell clones toward leukaemia in a few patients. Predicting who could let us choose therapies more safely.","summary":"This open question asks which patients' blood clones will become leukaemia after treatment: PARP inhibitors, platinum and radioligand drugs push pre-existing clones toward leukaemia in a few patients. Therapy-related myeloid neoplasms follow PPM1D and TP53 clonal haematopoiesis; incidence after PARP inhibitors is low but rising with longer use and Radioligand therapy (beta emitters), see Clonal haematopoiesis (CHIP). The hypothesis is that baseline CHIP genotype and variant allele fraction, with the planned genotoxic exposure, predict therapy-related MDS and AML well enough to guide drug choice and monitoring (Bolton 2020). The test is a prospective registry with baseline CHIP sequencing before these therapies, relevant to Acute myeloid leukaemia, Ovarian cancer and Prostate cancer.","asOf":"2026-09-08","links":[{"label":"Jaiswal: clonal haematopoiesis, the pre-leukaemic clones in most people over 70 (New England Journal of Medicine 2014)","url":"https://doi.org/10.1056/NEJMoa1408617"}],"tags":["mechanism","open-question"],"related":[],"cancers":["aml","ovarian","prostate"],"sections":[],"technologies":["parp-inhibitor","radioligand-therapy","liquid-biopsy"],"targets":["parp","tp53"],"drugs":[],"companies":[],"institutions":["dana-farber","mskcc"],"pathways":["clonal-haematopoiesis","ddr"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-vogelstein-surfing-p53-network-nature-2000"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Baseline CHIP genotype and VAF, combined with the planned genotoxic exposure, predicts therapy-related MDS/AML well enough to guide drug choice and monitoring.","rationale":"Bolton 2020 described the fitness landscapes of these clones under therapy, and the populations on long-term PARP inhibitors and 177Lu therapies are growing.","test":"Prospective registry with baseline CHIP sequencing in patients starting PARP inhibitors or radioligand therapy, validating a risk score; randomised monitoring intensity trial.","maturity":"preclinical-evidence"},{"id":"idea-acc-biosimilar-prequalification-pool","kind":"idea","name":"WHO prequalification plus pooled demand to push biosimilar prices below 10% of the originator","aka":[],"tldr":"Biosimilars of trastuzumab, rituximab and bevacizumab have existed for years, but poorer countries cannot assess biologics themselves and place small fragmented orders. Extending WHO prequalification, begun with trastuzumab in 2019, to every oncology biosimilar and pooling procurement would give buyers assurance and makers volume, aiming below a tenth of originator prices.","summary":"Biosimilars of trastuzumab, rituximab, and bevacizumab have been on the market for years, but uptake in LMICs is limited by regulatory capacity to assess biologics, fear of poor-quality products, and small, fragmented orders. WHO prequalification of biosimilars began with trastuzumab in 2019. Extending prequalification to the full oncology biosimilar set and coupling it with pooled procurement (through PAHO's Strategic Fund, UNICEF, or a new mechanism) would give buyers assurance and manufacturers volume.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Most of the world has almost no cancer care): WHO fact sheet, Cancer","url":"https://www.who.int/news-room/fact-sheets/detail/cancer"}],"tags":[],"related":[],"cancers":["breast-her2-positive","dlbcl"],"sections":[],"technologies":["monoclonal-antibody"],"targets":[],"drugs":["trastuzumab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-global-access","b-drug-pricing","b-regulatory-fragmentation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Prequalified biosimilars purchased through a pooled mechanism will be available in at least 20 additional low-income countries within three years at prices below 10% of the originator's high-income list price.","rationale":"Prequalification did this for HIV antiretrovirals and vaccines; biologics are more complex to assess, but the assessment is done once and used by many.","test":"Track prequalification throughput, participating country count, price per vial, and share of eligible patients receiving trastuzumab for HER2-positive breast cancer in participating versus non-participating countries.","maturity":"early-clinical","actor":"regulator","cost":"medium","horizonYears":3},{"id":"idea-prev-li-fraumeni-mri-plus-cfdna","kind":"idea","name":"Whole-body MRI plus blood DNA surveillance for people with Li-Fraumeni syndrome","aka":[],"tldr":"People with an inherited TP53 mutation face a near-certain lifetime cancer risk. Yearly whole-body MRI catches cancers early; adding blood DNA tests may catch them earlier still.","summary":"People with an inherited TP53 mutation face a near-certain lifetime cancer risk, so this idea builds a global Li-Fraumeni registry with standardised whole-body MRI surveillance plus prospective cell-free DNA and fragmentomics testing, to learn whether blood adds lead time over imaging. The Toronto Protocol of whole-body MRI, brain MRI and ultrasound already improved outcomes, the very high prior probability makes positive predictive value acceptable, and the multiplicity of tumour types favours a tumour-agnostic blood test. The test follows a 1,000-carrier prospective cohort for five years. At early-clinical maturity it addresses the bottlenecks Inherited risk is mostly unidentified and The hardest cancers are found late.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Inherited risk is mostly unidentified): Childers et al., National estimates of genetic testing in women with breast or ovarian cancer (JCO 2017)","url":"https://doi.org/10.1200/JCO.2017.73.6314"}],"tags":[],"related":[],"cancers":["sarcoma"],"sections":["prevention","imaging"],"technologies":["whole-body-mri","liquid-biopsy"],"targets":["tp53"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-hereditary-risk","b-early-detection"],"keyPapers":["paper-vogelstein-surfing-p53-network-nature-2000","paper-childers-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Adding cell-free DNA surveillance to imaging detects at least 30% of incident cancers before imaging, with lead time of six months or more.","rationale":"Very high prior probability makes positive predictive value acceptable, and the multiplicity of tumour types favours a tumour-agnostic blood test.","test":"Follow a 1,000-carrier prospective cohort over five years.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":5},{"id":"idea-moon-validated-digital-twins","kind":"idea","name":"Whole-patient digital twins validated in prospective randomised trials","aka":[],"tldr":"Build a computer model of each patient's cancer and body that simulates how different treatments would go, and prove in a proper trial that choosing treatment with the model helps.","summary":"Multimodal models combining genomics, pathology, imaging, pharmacokinetics and clinical history increasingly predict outcomes, but no digital twin has been validated as a decision tool in a randomised trial. The proposal is an open framework: standardised inputs, mechanistic plus learned components, calibration on federated real-world and trial data, and a series of randomised trials in which treatment selection assisted by the twin is compared with standard multidisciplinary decision-making, with regulators engaged on the evidence standard.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (AI that is built but not validated or deployed): Wu et al., How medical AI devices are evaluated: limitations and recommendations from an analysis of FDA approvals (Nature Medicine 2021)","url":"https://doi.org/10.1038/s41591-021-01312-x"}],"tags":[],"related":["idea-multimodal-foundation-model"],"cancers":[],"sections":[],"technologies":["pathology-foundation-model","digital-pathology-ai"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-ai-validation","b-combination-space","b-preclinical-models"],"keyPapers":["paper-wu-nat-med"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Twin-assisted selection improves progression-free survival or reduces toxicity in at least one common indication in a randomised trial, establishing an evidence standard for oncology decision AI.","rationale":"Retrospective accuracy has not translated into clinical benefit for most oncology AI; only prospective randomised evaluation can establish whether models change outcomes, and doing it once creates the pathway.","test":"Randomised trial in second-line lung or colorectal cancer of twin-assisted versus standard treatment choice; primary endpoint progression-free survival, secondary toxicity and cost.","maturity":"speculative","actor":"research","cost":"large","horizonYears":8},{"id":"idea-tr1-win-ratio-net-benefit-endpoint","kind":"idea","name":"Win-ratio endpoints that weigh survival, toxicity and quality of life together","aka":[],"tldr":"Every patient on the new drug is compared with every patient on the old one: who lived longer, and if equal, who had fewer serious side effects, and if still equal, who felt better. The share of 'wins' becomes the result.","summary":"Net benefit endpoints (win ratio, generalised pairwise comparisons, desirability of outcome ranking) rank prioritised outcomes hierarchically across all patient pairs. Cardiology adopted the win ratio for composite endpoints; oncology has used it only in exploratory analyses. The proposal is a pre-specified net-benefit endpoint with a published hierarchy (OS, then grade 3+ toxicity, then QoL deterioration) as a co-primary or key secondary in phase 3.","asOf":"2026-09-08","links":[{"label":"ESMO Magnitude of Clinical Benefit Scale","url":"https://www.esmo.org/guidelines/esmo-mcbs"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":["esmo"],"pathways":[],"terms":["os","pfs","irae"],"trials":[],"people":["nathan-cherny"],"bottlenecks":["b-trial-design","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Net-benefit endpoints will separate regimens that PFS ranks as equivalent, will correlate better with patient preference studies than PFS, and will be accepted by regulators as supportive evidence within five years.","rationale":"Composite endpoints that ignore severity ordering are crude; hierarchical pairwise comparison uses the same data more efficiently and encodes what patients say they value.","test":"Apply the endpoint retrospectively to completed trials with individual patient data (e.g., through data-sharing platforms) and compare rankings to PFS and to ESMO-MCBS grades; then pre-specify it in a cooperative-group trial.","maturity":"speculative","actor":"research","cost":"small","horizonYears":3},{"id":"idea-rejuv-rehabilitation-prescription-at-discharge","kind":"idea","name":"Write a rehabilitation prescription at the end of treatment, and fund it like a drug","aka":[],"tldr":"Exercise after colon cancer has a hazard ratio a drug would be licensed on. It is in the guidelines and in almost no budgets, because it is a staffed service rather than a product.","summary":"The end of treatment should produce a prescription, not a leaflet: a named programme, a named provider, a start date and a funded course. The components are already evidenced. Supervised aerobic and resistance training at the dose the American College of Sports Medicine roundtable specifies. Cognitive behavioural therapy for insomnia and for fatigue. Decongestive therapy and supervised resistance training for lymphoedema. Vocational rehabilitation where someone intends to return to work. Dietetic input where there is malnutrition or sarcopenia.\n\nWhat is missing is the financing instrument. A drug has a marketing authorisation, a payment code and a tariff; an exercise programme with CHALLENGE's hazard ratio has none of those, so it is recommended by every guideline and delivered by whoever has spare capacity. The specific proposal here is narrower than a general call for more rehabilitation: create a reimbursable bundle triggered by the completion of curative treatment, with the components fixed, uptake audited, and the audit published by provider.\n\nThe cost is real and should be stated. A supervised programme is staff time, and the workforce that would deliver it is already short. The counterargument is the trial evidence and the 2.4 million follow-up oncology appointments England recorded in a single year, a large share of which exist to reassure rather than to find anything.","asOf":"2026-10-02","links":[{"label":"Courneya et al., Structured exercise after adjuvant chemotherapy for colon cancer, the CHALLENGE trial (NEJM 2025;393:13-25)","url":"https://doi.org/10.1056/NEJMoa2502760"},{"label":"Campbell et al., Exercise guidelines for cancer survivors: consensus statement from international multidisciplinary roundtable (Medicine and Science in Sports and Exercise 2019;51:2375-2390)","url":"https://doi.org/10.1249/MSS.0000000000002116"},{"label":"Mustian et al., Comparison of pharmaceutical, psychological and exercise treatments for cancer-related fatigue: a meta-analysis (JAMA Oncology 2017;3:961)","url":"https://doi.org/10.1001/jamaoncol.2016.6914"},{"label":"Department of Health, Living With and Beyond Cancer: Taking Action to Improve Outcomes (England, 29 March 2013)","url":"https://www.gov.uk/government/publications/living-with-and-beyond-cancer-taking-action-to-improve-outcomes"},{"label":"ClinicalTrials.gov NCT06723899","url":"https://clinicaltrials.gov/study/NCT06723899"}],"tags":["rejuvenation","survivorship","open-problem","rehabilitation","commissioning"],"related":["exercise-prescription-after-cancer","structured-exercise-survivorship","rejuv-frontier-what-works","rejuv-mind-access-to-psychological-care","rejuv-life-return-to-work","idea-bio2-exercise-reimbursement","idea-acc-return-to-work-rehabilitation","rejuv-trial-canwork","rejuv-history-ncsi-england","rejuvenation-roadmap"],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["rejuv-agenda-rehabilitation-not-commissioned","b-survivorship","b-care-fragmentation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A funded, audited rehabilitation bundle triggered at the end of curative treatment increases uptake of the interventions that already have randomised evidence, and improves function, return to work and, in the cancers where exercise has been tested, recurrence and survival.","rationale":"CHALLENGE showed eight-year overall survival of 90.3 against 83.2 per cent with a three-year coached exercise programme after colon cancer chemotherapy. A meta-analysis of 113 studies put exercise and psychological therapy far ahead of drugs for fatigue. And across this entire front the repeated finding is that these services are not commissioned: few services employ anyone to deliver supervised resistance training, referral pathways from oncology to gastroenterology for bowel injury rarely exist, and no health service OnCo could find commissions a named service for fear of recurrence.","test":"Implement the bundle as a funded pathway in one health system with a stepped-wedge rollout across centres, measuring uptake, function, return to work and, where the cancer and the intervention match the trial evidence, recurrence. CanWork's embedded cost-effectiveness analysis is the model for the economic arm.","maturity":"early-clinical","actor":"payer","cost":"large","horizonYears":5},{"id":"idea-bio1-wrn-msi-programme","kind":"idea","name":"WRN inhibitors: a second synthetic-lethal win for mismatch-repair cancers","aka":[],"tldr":"Cancers with faulty DNA proof-reading depend on one particular unwinding enzyme to survive. Blocking it kills them and spares normal cells.","summary":"Microsatellite-unstable cancers accumulate expanded TA repeats that form secondary structures requiring WRN helicase to resolve; WRN loss is selectively lethal in MSI-high lines, one of the strongest synthetic-lethal signals from CRISPR screens. WRN inhibitors and degraders have entered early clinical trials. The strategic proposal is to test WRN inhibition specifically in MSI-high tumours that have failed immunotherapy, a group with no good options.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The undruggable drivers): Dang et al., Drugging the 'undruggable' cancer targets (Nature Reviews Cancer 2017)","url":"https://doi.org/10.1038/nrc.2017.36"}],"tags":[],"related":[],"cancers":["colorectal","endometrial"],"sections":[],"technologies":["synthetic-lethality-approaches","crispr-screens"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["msi","synthetic-lethality","tumour-agnostic"],"trials":[],"people":[],"bottlenecks":["b-undruggable-targets","b-resistance"],"keyPapers":["paper-dang-nat-rev-cancer"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"WRN inhibition produces objective responses in MSI-high tumours that have progressed on checkpoint blockade, at a rate materially higher than that of available chemotherapy.","rationale":"The dependency is genotype-defined, near-binary and reproducible across laboratories, which is rare; MSI status is already tested routinely, so patient selection needs no new diagnostic.","test":"Tumour-agnostic phase 2 in MSI-high, immunotherapy-refractory cancers with a pre-specified response threshold and paired biopsies for target engagement.","maturity":"early-clinical","actor":"industry","cost":"medium","horizonYears":4},{"id":"idea-bio1-zebrafish-avatars","kind":"idea","name":"Zebrafish avatars for a drug answer within a week","aka":[],"tldr":"Tumour cells injected into transparent fish embryos grow in days, so several drugs can be compared in about a week, fast enough to help a patient who cannot wait.","summary":"Zebrafish patient-derived xenografts accept small cell numbers, are transparent for direct imaging of growth and metastasis, and give readouts in five to ten days at a fraction of mouse cost. Studies in colorectal and other cancers report concordance with patient outcomes. They lack an adaptive immune system and drug metabolism differs, so their role is rapid triage rather than definitive prediction.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Lab models that fail to predict what happens in patients): Wong, Siah & Lo, Estimation of clinical trial success rates (Biostatistics 2019)","url":"https://doi.org/10.1093/biostatistics/kxx069"}],"tags":[],"related":[],"cancers":["colorectal","pancreatic"],"sections":[],"technologies":["functional-drug-testing","pdx-models"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-preclinical-models"],"keyPapers":["paper-wong-biostatistics"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Zebrafish avatar drug ranking agrees with matched mouse PDX ranking in most cases and can be delivered in under two weeks from biopsy, making it usable in real clinical timeframes.","rationale":"Speed and sample requirement are the binding constraints on functional testing in advanced disease; a triage assay with even moderate accuracy has value if it narrows options before slower assays.","test":"Head-to-head on 50 patient samples: zebrafish, organoid and mouse rankings compared with each other and with the patient's response to the chosen regimen.","maturity":"preclinical-evidence","actor":"research","cost":"small","horizonYears":3}]