{"id":"frontier-2035","name":"Radical oncology: what could change the war by 2035","route":"/roadmaps/frontier-2035/","eras":[{"era":"Now (randomised data exists)","title":"Ideas already being tested against a control arm","description":"Microbiome modulation, spatially fractionated radiotherapy, sonodynamic therapy in glioblastoma, GDF-15 blockade for cachexia, and repurposed cheap drugs all have randomised or registrational trials running in 2026. These are the frontier ideas closest to a guideline: each has a defined population, a comparator, and a readout inside a few years. Cachexia therapy is the likeliest first approval in a domain with no approved drug at all.","status":"current","refs":[{"id":"microbiome-modulation-io","kind":"technology","name":"Microbiome modulation to unlock immunotherapy","route":"/technologies/microbiome-modulation-io/","status":"phase-2","tldr":"Changing the gut bacteria of a patient whose immunotherapy stopped working, in the hope of restarting the response."},{"id":"lattice-radiotherapy","kind":"technology","name":"Lattice and GRID radiotherapy","route":"/technologies/lattice-radiotherapy/","status":"phase-2","tldr":"Lattice radiotherapy deliberately treats a bulky tumour unevenly, placing peaks of tumour-destroying dose at spaced points inside it while the tissue between receives far less, relying on bystander and immune effects to extend the kill. It runs on standard linear accelerators, but evidence is mostly palliative and single-arm, and the mechanism is unsettled."},{"id":"sonodynamic-therapy","kind":"technology","name":"Sonodynamic therapy","route":"/technologies/sonodynamic-therapy/","status":"phase-2","tldr":"A drug that does nothing until ultrasound hits it, then kills the cells that took it up. Being tested in brain tumours because sound reaches where light cannot."},{"id":"cachexia-therapy","kind":"technology","name":"Cachexia-directed therapy (GDF-15 blockade)","route":"/technologies/cachexia-therapy/","status":"phase-3","tldr":"Cachexia-directed therapy treats cancer wasting by blocking GDF-15, a hormone that rises in advanced cancer and acts on the brainstem to suppress appetite. Pfizer's antibody ponsegromab improved weight in a phase 2 trial and is in phase 2/3 in pancreatic cancer cachexia; whether weight gain translates into function is the open question."},{"id":"drug-repurposing","kind":"technology","name":"Systematic drug repurposing","route":"/technologies/drug-repurposing/","status":"phase-3","tldr":"Testing cheap old drugs, aspirin, metformin, statins, beta-blockers, as cancer treatments, because they are safe, available and sometimes work."},{"id":"radiodynamic-therapy","kind":"technology","name":"Radiodynamic therapy and radiosensitising nanoparticles","route":"/technologies/radiodynamic-therapy/","status":"phase-2","tldr":"Nanoparticles that turn ordinary radiotherapy X-rays into a much bigger dose exactly where they sit."}],"trials":[],"papers":[]},{"era":"By 2027 (early clinical, readouts imminent)","title":"Living drugs, logic gates, and designed proteins reach decision points","description":"Engineered bacteria, logic-gated cell therapies, molecular glue platforms, and de novo designed binders all have first-in-human programmes running. The question each faces is the same: does the elegant mechanism survive contact with a heterogeneous human tumour? Expect most to disappoint on response rate while establishing safety, which is how bispecific antibodies and ADCs also began.","status":"emerging","refs":[{"id":"engineered-bacteria-therapy","kind":"technology","name":"Engineered bacteria as living cancer drugs","route":"/technologies/engineered-bacteria-therapy/","status":"phase-2","tldr":"Bacteria that seek out the low-oxygen core of tumours, then manufacture a drug on the spot."},{"id":"logic-gated-therapeutics","kind":"technology","name":"Logic-gated therapeutics (AND, NOT gates)","route":"/technologies/logic-gated-therapeutics/","status":"phase-1","tldr":"Cells or drugs that fire only when two conditions are true at once, so healthy tissue expressing just one of them is spared."},{"id":"molecular-glue-platforms","kind":"technology","name":"Molecular glue discovery platforms","route":"/technologies/molecular-glue-platforms/","status":"phase-1","tldr":"Molecular glues are small molecules that stick two proteins together so the cell destroys one of them. They are smaller and more drug-like than bifunctional degraders."},{"id":"de-novo-protein-design","kind":"technology","name":"De novo designed protein binders","route":"/technologies/de-novo-protein-design/","status":"phase-1","tldr":"Designing a protein from scratch on a computer to grip a chosen target, instead of finding one in an animal or a library."},{"id":"in-situ-vaccination","kind":"technology","name":"In situ vaccination","route":"/technologies/in-situ-vaccination/","status":"phase-2","tldr":"Treating one tumour so aggressively that the immune system learns to attack every other one, using the tumour itself as the vaccine."},{"id":"histotripsy-immune-priming","kind":"technology","name":"Histotripsy as an immune primer","route":"/technologies/histotripsy-immune-priming/","status":"phase-1","tldr":"Destroying a tumour mechanically with sound, rather than heat, leaves the debris intact enough for the immune system to learn from it."},{"id":"radionuclide-parp-combination","kind":"technology","name":"Radioligand plus DNA-repair inhibitor combinations","route":"/technologies/radionuclide-parp-combination/","status":"phase-1","tldr":"Adding a PARP or ATR inhibitor to a radioactive drug so the tumour cannot repair the damage the radiation causes."}],"trials":[],"papers":[]},{"era":"By 2030 (physics and chemistry maturing)","title":"Radiation and radiopharmaceuticals get a second act","description":"Auger emitters, contained alpha nanogenerators, proton arc delivery, and very-high-energy electrons are all limited today by engineering rather than biology: isotope supply, daughter recoil, gantry speed, and dosimetry at ultra-high dose rate. Those are tractable problems with capital behind them. If FLASH sparing is real in humans, deep FLASH by electron or proton arc would be the largest change to radiotherapy since intensity modulation.","status":"emerging","refs":[{"id":"auger-electron-therapy","kind":"technology","name":"Auger-electron therapy","route":"/technologies/auger-electron-therapy/","status":"preclinical","tldr":"Auger-electron therapy uses radioactive atoms such as iodine-125 or terbium-161 that release cascades of low-energy electrons travelling only nanometres to micrometres, so they kill a cell only if the atom sits on or inside its DNA and spare the neighbours. Terbium-161 can replace lutetium-177 in existing PSMA ligands; true nuclear delivery remains preclinical."},{"id":"alpha-nanogenerators","kind":"technology","name":"Alpha-emitter nanogenerators and daughter trapping","route":"/technologies/alpha-nanogenerators/","status":"preclinical","tldr":"Actinium-225 releases four alpha particles as it decays, but the daughters escape and irradiate the kidneys and salivary glands. Nanocarriers try to hold them in place."},{"id":"proton-arc-therapy","kind":"technology","name":"Proton arc therapy","route":"/technologies/proton-arc-therapy/","status":"phase-1","tldr":"Rotating the proton beam continuously around the patient instead of firing from a few fixed angles, to spread the entrance dose and sharpen the target dose."},{"id":"vhee-radiotherapy","kind":"technology","name":"Very-high-energy electron therapy","route":"/technologies/vhee-radiotherapy/","status":"preclinical","tldr":"VHEE radiotherapy fires electrons at 100 to 250 MeV, energies that reach deep tumours and can be steered by magnets, aiming to deliver FLASH-speed radiation from a machine smaller and cheaper than a proton facility. It is still at the accelerator-development and preclinical stage: no patient had been treated by September 2026."},{"id":"magnetic-nanoparticle-hyperthermia","kind":"technology","name":"Magnetic nanoparticle hyperthermia","route":"/technologies/magnetic-nanoparticle-hyperthermia/","status":"phase-2","tldr":"Magnetic nanoparticle hyperthermia injects iron-oxide nanoparticles into a tumour and heats them from outside with an alternating magnetic field."},{"id":"photothermal-nanoparticles","kind":"technology","name":"Photothermal (plasmonic) nanoparticle ablation","route":"/technologies/photothermal-nanoparticles/","status":"phase-2","tldr":"Gold nanoshells that accumulate in a tumour and cook it when a near-infrared laser is shone on them."}],"trials":[],"papers":[]},{"era":"By 2030 (detection and decision-making)","title":"Monitoring becomes continuous and selection becomes spatial","description":"Fragmentomics, breath analysis, and near-continuous ctDNA sampling all push detection from an annual event towards a running signal, while spatial omics and organoid testing push treatment choice from genotype towards phenotype and architecture. The gating question for every one of them is not sensitivity but utility: acting earlier has to change outcomes, and no randomised trial has yet shown that for continuous monitoring.","status":"emerging","refs":[{"id":"continuous-ctdna-monitoring","kind":"technology","name":"Continuous and near-continuous ctDNA monitoring","route":"/technologies/continuous-ctdna-monitoring/","status":"concept","tldr":"Instead of testing blood every three months, sampling constantly, so a relapse is caught the week it starts."},{"id":"breath-vocs","kind":"technology","name":"Breath and volatile-organic-compound detection","route":"/technologies/breath-vocs/","status":"phase-2","tldr":"Smelling cancer: measuring the trace chemicals a tumour puts into exhaled breath."},{"id":"spatial-omics-guided-therapy","kind":"technology","name":"Spatial-omics-guided treatment selection","route":"/technologies/spatial-omics-guided-therapy/","status":"emerging","tldr":"Choosing treatment from a map of where each cell type sits in the tumour, not just from a list of its mutations."},{"id":"organoid-guided-therapy-scale","kind":"technology","name":"Organoid-guided therapy at scale","route":"/technologies/organoid-guided-therapy-scale/","status":"phase-2","tldr":"Organoid-guided therapy means routinely growing a piece of each patient's tumour and testing drugs on it before choosing, rather than relying on genetics alone."},{"id":"digital-twins-trials","kind":"technology","name":"Digital twins and virtual control arms","route":"/technologies/digital-twins-trials/","status":"emerging","tldr":"Using a model of what would have happened to a patient on standard treatment, so fewer people have to be randomised to it."},{"id":"n-of-1-platforms","kind":"technology","name":"N-of-1 and rapid platform trials","route":"/technologies/n-of-1-platforms/","status":"emerging","tldr":"Building a trial around one patient, or letting one trial swap drugs in and out as evidence accumulates."},{"id":"total-body-pet-screening","kind":"technology","name":"Total-body PET for screening and ultra-low-dose imaging","route":"/technologies/total-body-pet-screening/","status":"concept","tldr":"Scanners sensitive enough to image the whole body in seconds at a fraction of the radiation dose, which raises the question of whether healthy people should be scanned at all."}],"trials":[],"papers":[]},{"era":"By 2035 (needs a delivery breakthrough)","title":"Writing to the genome and the epigenome inside a tumour","description":"In vivo base and prime editing, epigenetic silencing, antibody-oligonucleotide conjugates, and programmable DNA-targeting drugs share one blocker: getting a large, charged molecule into most cells of a solid tumour. Liver-directed editing is already in the clinic, so the chemistry works; the tumour delivery problem has resisted thirty years of effort. If it is solved, undruggable drivers such as MYC and TP53 loss become addressable and much of this roadmap is rewritten.","status":"speculative","refs":[{"id":"in-vivo-gene-editing-cancer","kind":"technology","name":"In vivo base and prime editing for cancer","route":"/technologies/in-vivo-gene-editing-cancer/","status":"concept","tldr":"In vivo base and prime editing would rewrite a cancer's DNA letter by letter inside the body. It works in the liver for inherited disease; nobody has yet corrected a cancer this way in a person."},{"id":"epigenetic-editing","kind":"technology","name":"Epigenetic editing (durable gene silencing)","route":"/technologies/epigenetic-editing/","status":"concept","tldr":"Switching a gene off for good without changing the DNA sequence, by writing chemical marks onto it."},{"id":"antibody-oligonucleotide-conjugates","kind":"technology","name":"Antibody-oligonucleotide conjugates","route":"/technologies/antibody-oligonucleotide-conjugates/","status":"preclinical","tldr":"An ADC that carries a gene-silencing strand instead of a chemotherapy, so it can switch a protein off rather than poison the cell."},{"id":"programmable-dna-targeting-therapeutics","kind":"technology","name":"Programmable DNA-targeting therapeutics","route":"/technologies/programmable-dna-targeting-therapeutics/","status":"preclinical","tldr":"Programmable DNA-targeting therapeutics are an experimental idea: a drug that reads a cell's DNA, recognises a cancer-specific sequence, and kills only cells that carry it. Change the guide, and the same drug becomes a new drug."},{"id":"self-amplifying-rna","kind":"technology","name":"Self-amplifying and circular RNA therapeutics","route":"/technologies/self-amplifying-rna/","status":"phase-1","tldr":"RNA drugs that copy themselves inside the cell, or are made as a loop so they last longer. Both aim to get more protein from a smaller dose."},{"id":"exosome-therapeutics","kind":"technology","name":"Engineered exosomes as drug carriers","route":"/technologies/exosome-therapeutics/","status":"phase-1","tldr":"Loading the tiny vesicles cells naturally use to talk to each other with a cancer drug, so the body treats the carrier as its own."},{"id":"dna-origami-nanorobots","kind":"technology","name":"DNA origami nanorobots","route":"/technologies/dna-origami-nanorobots/","status":"preclinical","tldr":"Folded DNA machines that open only when they touch a tumour, releasing a payload or clotting the tumour's blood supply."}],"trials":[],"papers":[]},{"era":"By 2035 (attacking the host, not the tumour)","title":"Treating the soil rather than the seed","description":"Stromal CAR-T, nerve blockade, senescence clearance, mechanical decompression, and targeting the tumour's own microbes all treat the environment a cancer needs rather than the cancer itself. The attraction is that the host does not mutate. The risk is visible in the record: PEGPH20 failed, FAP CAR-T caused cachexia in mice, and broad antibiotics blunt immunotherapy. Success here probably requires far better spatial measurement first.","status":"speculative","refs":[{"id":"stroma-directed-car","kind":"technology","name":"CAR-T against stroma: fibroblasts and myeloid cells","route":"/technologies/stroma-directed-car/","status":"preclinical","tldr":"Instead of attacking the cancer cell, engineering T cells to strip away the scaffolding and the suppressive immune cells that protect it."},{"id":"cancer-neuroscience","kind":"pathway","name":"Cancer neuroscience (nerve-tumour signalling)","route":"/pathways/cancer-neuroscience/","tldr":"Cancer neuroscience is the study of how tumours talk to nerves. Nerves grow into tumours and feed them signals; brain tumours even wire themselves into neural circuits. Cutting the conversation with common drugs such as beta-blockers is now being tested."},{"id":"senescence-targeting","kind":"technology","name":"Senolytics and senescence-directed therapy","route":"/technologies/senescence-targeting/","status":"preclinical","tldr":"Chemotherapy leaves behind zombie cells that will not divide but poison their neighbours. Senolytics aim to clear them."},{"id":"mechanobiology-therapy","kind":"technology","name":"Targeting tumour mechanics and pressure","route":"/technologies/mechanobiology-therapy/","status":"preclinical","tldr":"Stiff, high-pressure tumours squeeze their own blood vessels shut, keeping drugs out. Softening them is a way in."},{"id":"tumour-microbiome-targeting","kind":"technology","name":"Targeting the tumour's own microbes","route":"/technologies/tumour-microbiome-targeting/","status":"preclinical","tldr":"Some tumours contain bacteria and fungi that shelter cancer cells and break down chemotherapy. Killing them may make treatment work."},{"id":"hypoxia-activated-therapy","kind":"technology","name":"Hypoxia-activated prodrugs","route":"/technologies/hypoxia-activated-therapy/","status":"phase-2","tldr":"A harmless molecule that turns into a poison only where there is no oxygen, which in the body means inside a tumour."},{"id":"trained-innate-immunity","kind":"technology","name":"Trained innate immunity","route":"/technologies/trained-innate-immunity/","status":"phase-2","tldr":"Giving the innate immune system a memory, so monocytes and NK cells respond harder the next time they meet a tumour."}],"trials":[],"papers":[]},{"era":"Speculative (no human evidence)","title":"Ideas that are still physics and mouse data","description":"DNA origami nanorobots, phage-based delivery, and quantum-dot imaging agents have striking preclinical demonstrations and no clinical footprint. They belong on the map because the failure modes are known and specific, nuclease degradation, rapid clearance, heavy-metal toxicity, rather than vague. Any of them could move a horizon if a single delivery or materials problem is solved.","status":"speculative","refs":[{"id":"dna-origami-nanorobots","kind":"technology","name":"DNA origami nanorobots","route":"/technologies/dna-origami-nanorobots/","status":"preclinical","tldr":"Folded DNA machines that open only when they touch a tumour, releasing a payload or clotting the tumour's blood supply."},{"id":"phage-delivery","kind":"technology","name":"Bacteriophage-based tumour delivery","route":"/technologies/phage-delivery/","status":"preclinical","tldr":"Bacteriophage delivery uses viruses that infect bacteria, not human cells, as engineered shells whose coat proteins display tumour-homing peptides or antigens and carry drugs or vaccines. They are cheap and cannot replicate in people, but the work is preclinical: no oncology phage trial had reported efficacy by 2026, and the body clears them quickly."},{"id":"quantum-dot-imaging","kind":"technology","name":"Quantum-dot and molecular ultrasound imaging agents","route":"/technologies/quantum-dot-imaging/","status":"preclinical","tldr":"Brighter, longer-lasting fluorescent particles and targeted microbubbles that make tumours visible during surgery or on an ultrasound scan."},{"id":"chronotherapy","kind":"technology","name":"Chronotherapy: timing treatment to the body clock","route":"/technologies/chronotherapy/","status":"phase-2","tldr":"Giving the same drug at a different time of day, because the body clock changes how much damage it does and how well the immune system responds."},{"id":"metabolic-therapy","kind":"technology","name":"Metabolic therapy: starving the tumour of a nutrient","route":"/technologies/metabolic-therapy/","status":"phase-2","tldr":"Removing an amino acid or nutrient that certain tumours cannot make for themselves, while normal cells can."}],"trials":[],"papers":[]}],"watch":[]}