{"entity":{"id":"frontier-2035","kind":"roadmap","name":"Radical oncology: what could change the war by 2035","aka":[],"tldr":"Radical oncology is a horizon map of the wilder ideas in cancer, sorted by how close they are to mattering, with the reason each one might never arrive.","summary":"Most of what is celebrated as a breakthrough is an incremental gain on an existing modality. This roadmap collects the ideas that would change the shape of treatment rather than its slope: therapies that read DNA directly, living drugs, radiation delivered in milliseconds, and detection that runs continuously rather than annually.\n\nThe grouping is by horizon, from technologies already producing randomised data to ideas with no human evidence at all. Placement reflects the state of evidence in September 2026, not company timelines. Several steps will not happen: the failure record of hypoxia-activated prodrugs, metabolic therapy, and matrix-softening agents is a reminder that a clean mechanism is not a clinical benefit.","asOf":"2026-09-08","links":[],"tags":[],"related":[],"cancers":[],"sections":["drug-discovery","radiation","cell-therapy","early-detection"],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"steps":[{"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.","refs":["microbiome-modulation-io","lattice-radiotherapy","sonodynamic-therapy","cachexia-therapy","drug-repurposing","radiodynamic-therapy"],"status":"current"},{"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.","refs":["engineered-bacteria-therapy","logic-gated-therapeutics","molecular-glue-platforms","de-novo-protein-design","in-situ-vaccination","histotripsy-immune-priming","radionuclide-parp-combination"],"status":"emerging"},{"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.","refs":["auger-electron-therapy","alpha-nanogenerators","proton-arc-therapy","vhee-radiotherapy","magnetic-nanoparticle-hyperthermia","photothermal-nanoparticles"],"status":"emerging"},{"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.","refs":["continuous-ctdna-monitoring","breath-vocs","spatial-omics-guided-therapy","organoid-guided-therapy-scale","digital-twins-trials","n-of-1-platforms","total-body-pet-screening"],"status":"emerging"},{"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.","refs":["in-vivo-gene-editing-cancer","epigenetic-editing","antibody-oligonucleotide-conjugates","programmable-dna-targeting-therapeutics","self-amplifying-rna","exosome-therapeutics","dna-origami-nanorobots"],"status":"speculative"},{"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.","refs":["stroma-directed-car","cancer-neuroscience","senescence-targeting","mechanobiology-therapy","tumour-microbiome-targeting","hypoxia-activated-therapy","trained-innate-immunity"],"status":"speculative"},{"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.","refs":["dna-origami-nanorobots","phage-delivery","quantum-dot-imaging","chronotherapy","metabolic-therapy"],"status":"speculative"}],"watch":[]},"route":"/roadmaps/frontier-2035/","neighbours":{"section":[{"id":"cell-therapy","kind":"section","name":"Cell Therapy","route":"/fronts/cell-therapy/"},{"id":"drug-discovery","kind":"section","name":"Drug Discovery Platforms","route":"/fronts/drug-discovery/"},{"id":"early-detection","kind":"section","name":"Early Detection & Screening","route":"/fronts/early-detection/"},{"id":"radiation","kind":"section","name":"Radiation Therapy","route":"/fronts/radiation/"}],"technology":[{"id":"alpha-nanogenerators","kind":"technology","name":"Alpha-emitter nanogenerators and daughter trapping","route":"/technologies/alpha-nanogenerators/"},{"id":"antibody-oligonucleotide-conjugates","kind":"technology","name":"Antibody-oligonucleotide conjugates","route":"/technologies/antibody-oligonucleotide-conjugates/"},{"id":"auger-electron-therapy","kind":"technology","name":"Auger-electron therapy","route":"/technologies/auger-electron-therapy/"},{"id":"phage-delivery","kind":"technology","name":"Bacteriophage-based tumour delivery","route":"/technologies/phage-delivery/"},{"id":"breath-vocs","kind":"technology","name":"Breath and volatile-organic-compound detection","route":"/technologies/breath-vocs/"},{"id":"cachexia-therapy","kind":"technology","name":"Cachexia-directed therapy (GDF-15 blockade)","route":"/technologies/cachexia-therapy/"},{"id":"stroma-directed-car","kind":"technology","name":"CAR-T against stroma: fibroblasts and myeloid cells","route":"/technologies/stroma-directed-car/"},{"id":"chronotherapy","kind":"technology","name":"Chronotherapy: timing treatment to the body clock","route":"/technologies/chronotherapy/"},{"id":"continuous-ctdna-monitoring","kind":"technology","name":"Continuous and near-continuous ctDNA monitoring","route":"/technologies/continuous-ctdna-monitoring/"},{"id":"de-novo-protein-design","kind":"technology","name":"De novo designed protein binders","route":"/technologies/de-novo-protein-design/"},{"id":"digital-twins-trials","kind":"technology","name":"Digital twins and virtual control arms","route":"/technologies/digital-twins-trials/"},{"id":"dna-origami-nanorobots","kind":"technology","name":"DNA origami nanorobots","route":"/technologies/dna-origami-nanorobots/"},{"id":"engineered-bacteria-therapy","kind":"technology","name":"Engineered bacteria as living cancer drugs","route":"/technologies/engineered-bacteria-therapy/"},{"id":"exosome-therapeutics","kind":"technology","name":"Engineered exosomes as drug carriers","route":"/technologies/exosome-therapeutics/"},{"id":"epigenetic-editing","kind":"technology","name":"Epigenetic editing (durable gene silencing)","route":"/technologies/epigenetic-editing/"},{"id":"histotripsy-immune-priming","kind":"technology","name":"Histotripsy as an immune primer","route":"/technologies/histotripsy-immune-priming/"},{"id":"hypoxia-activated-therapy","kind":"technology","name":"Hypoxia-activated prodrugs","route":"/technologies/hypoxia-activated-therapy/"},{"id":"in-situ-vaccination","kind":"technology","name":"In situ vaccination","route":"/technologies/in-situ-vaccination/"},{"id":"in-vivo-gene-editing-cancer","kind":"technology","name":"In vivo base and prime editing for cancer","route":"/technologies/in-vivo-gene-editing-cancer/"},{"id":"lattice-radiotherapy","kind":"technology","name":"Lattice and GRID radiotherapy","route":"/technologies/lattice-radiotherapy/"},{"id":"logic-gated-therapeutics","kind":"technology","name":"Logic-gated therapeutics (AND, NOT gates)","route":"/technologies/logic-gated-therapeutics/"},{"id":"magnetic-nanoparticle-hyperthermia","kind":"technology","name":"Magnetic nanoparticle hyperthermia","route":"/technologies/magnetic-nanoparticle-hyperthermia/"},{"id":"metabolic-therapy","kind":"technology","name":"Metabolic therapy: starving the tumour of a nutrient","route":"/technologies/metabolic-therapy/"},{"id":"microbiome-modulation-io","kind":"technology","name":"Microbiome modulation to unlock immunotherapy","route":"/technologies/microbiome-modulation-io/"},{"id":"molecular-glue-platforms","kind":"technology","name":"Molecular glue discovery platforms","route":"/technologies/molecular-glue-platforms/"},{"id":"n-of-1-platforms","kind":"technology","name":"N-of-1 and rapid platform trials","route":"/technologies/n-of-1-platforms/"},{"id":"organoid-guided-therapy-scale","kind":"technology","name":"Organoid-guided therapy at scale","route":"/technologies/organoid-guided-therapy-scale/"},{"id":"photothermal-nanoparticles","kind":"technology","name":"Photothermal (plasmonic) nanoparticle ablation","route":"/technologies/photothermal-nanoparticles/"},{"id":"programmable-dna-targeting-therapeutics","kind":"technology","name":"Programmable DNA-targeting therapeutics","route":"/technologies/programmable-dna-targeting-therapeutics/"},{"id":"proton-arc-therapy","kind":"technology","name":"Proton arc therapy","route":"/technologies/proton-arc-therapy/"},{"id":"quantum-dot-imaging","kind":"technology","name":"Quantum-dot and molecular ultrasound imaging agents","route":"/technologies/quantum-dot-imaging/"},{"id":"radiodynamic-therapy","kind":"technology","name":"Radiodynamic therapy and radiosensitising nanoparticles","route":"/technologies/radiodynamic-therapy/"},{"id":"radionuclide-parp-combination","kind":"technology","name":"Radioligand plus DNA-repair inhibitor combinations","route":"/technologies/radionuclide-parp-combination/"},{"id":"self-amplifying-rna","kind":"technology","name":"Self-amplifying and circular RNA therapeutics","route":"/technologies/self-amplifying-rna/"},{"id":"senescence-targeting","kind":"technology","name":"Senolytics and senescence-directed therapy","route":"/technologies/senescence-targeting/"},{"id":"sonodynamic-therapy","kind":"technology","name":"Sonodynamic therapy","route":"/technologies/sonodynamic-therapy/"},{"id":"spatial-omics-guided-therapy","kind":"technology","name":"Spatial-omics-guided treatment selection","route":"/technologies/spatial-omics-guided-therapy/"},{"id":"drug-repurposing","kind":"technology","name":"Systematic drug repurposing","route":"/technologies/drug-repurposing/"},{"id":"tumour-microbiome-targeting","kind":"technology","name":"Targeting the tumour's own microbes","route":"/technologies/tumour-microbiome-targeting/"},{"id":"mechanobiology-therapy","kind":"technology","name":"Targeting tumour mechanics and pressure","route":"/technologies/mechanobiology-therapy/"},{"id":"total-body-pet-screening","kind":"technology","name":"Total-body PET for screening and ultra-low-dose imaging","route":"/technologies/total-body-pet-screening/"},{"id":"trained-innate-immunity","kind":"technology","name":"Trained innate immunity","route":"/technologies/trained-innate-immunity/"},{"id":"vhee-radiotherapy","kind":"technology","name":"Very-high-energy electron therapy","route":"/technologies/vhee-radiotherapy/"}],"pathway":[{"id":"cancer-neuroscience","kind":"pathway","name":"Cancer neuroscience (nerve-tumour signalling)","route":"/pathways/cancer-neuroscience/"}],"roadmap":[{"id":"devices-roadmap","kind":"roadmap","name":"Devices and physical therapies roadmap: heat and light → electric fields and focused sound → drug-releasing implants","route":"/roadmaps/devices-roadmap/"},{"id":"epigenetics-roadmap","kind":"roadmap","name":"Epigenetic therapy roadmap: loosening silenced genes → mutation-specific enzymes → editing the epigenome","route":"/roadmaps/epigenetics-roadmap/"},{"id":"radiation-roadmap","kind":"roadmap","name":"Radiotherapy roadmap: X-rays → shaped beams → fewer fractions, particles and FLASH","route":"/roadmaps/radiation-roadmap/"}]}}