[{"id":"antigen-presentation-immunoediting","name":"Antigen presentation & immune editing","tldr":"How the immune system sees cancer, and how cancer learns to hide. Tumours display fragments of their proteins on MHC molecules; T cells kill the ones they recognise; the survivors are the ones that stopped showing fragments or switched on brakes.","route":"/pathways/antigen-presentation-immunoediting/","kind":"pathway","schematic":{"id":"neoantigen-mrna-vaccine","sections":["immunotherapy"]},"facets":{"kind":["Pathway"],"cancers":[],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[],"tags":[]},"sortKeys":{"year":0}},{"id":"idea-ecdna-targeting","name":"Attack extrachromosomal DNA, the engine of oncogene amplification","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.","route":"/ideas/idea-ecdna-targeting/","kind":"idea","cancerIcon":"glioblastoma","facets":{"kind":["Idea"],"cancers":["Glioma & glioblastoma","Sarcomas","Gastric & gastro-oesophageal junction cancer"],"year":[]},"cols":{"kind":{"facet":"kind","value":"Idea","tip":"Hypotheses and new directions, linked to the evidence."},"cancers":[{"label":"Glioma & glioblastoma","href":"/cancers/glioblastoma/","tip":"Gliomas are now diagnosed by molecular class, and three classes got their first targeted drugs in 2024-25 (vorasidenib for IDH-mutant glioma, tovorafenib for BRAF-altered paediatric glioma, dordaviprone for H3 K27M). Glioblastoma itself is the hardest to treat and has kept the same standard since 2005; CAR-T delivered into the brain and focused-ultrasound drug delivery are the live directions."},{"label":"Sarcomas","href":"/cancers/sarcoma/","tip":"Sarcomas are dozens of rare cancers of bone and connective tissue. GIST was the first solid tumour cured-in-practice by a targeted pill; synovial sarcoma got the first TCR-T therapy."},{"label":"Gastric & gastro-oesophageal junction cancer","href":"/cancers/gastric/","tip":"A cancer with three new targets in five years: Claudin 18.2, FGFR2b, and HER2 with new ADCs, plus immunotherapy in first line."}],"tags":[{"label":"open-question","href":"/tagged/open-question/","tip":"Every record tagged open-question."}]},"sortKeys":{"year":0}},{"id":"autophagy","name":"Autophagy","tldr":"Autophagy is the cell's recycling programme. Cancer cells, especially pancreatic and RAS-driven tumours, use it to survive starvation and drug stress, which is why hydroxychloroquine, an old malaria drug that blocks it, keeps appearing in trials.","route":"/pathways/autophagy/","kind":"pathway","cancerIcon":"pancreatic","facets":{"kind":["Pathway"],"cancers":["Pancreatic ductal adenocarcinoma"],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[{"label":"Pancreatic ductal adenocarcinoma","href":"/cancers/pancreatic/","tip":"Almost every pancreatic tumour carries a KRAS mutation, and for the first time drugs against it work: daraxonrasib nearly doubled survival in previously treated disease in 2026. Pancreatic cancer has been the hardest common cancer to treat once advanced; that is what is starting to change."}],"tags":[]},"sortKeys":{"year":0}},{"id":"base-excision-repair-parp","name":"Base excision repair, PARP & alkylation damage","tldr":"Tens of thousands of times a day a single DNA letter is oxidised or chemically scarred. A small crew snips it out and PARP marks the nick so it gets sealed. PARP inhibitors do not just switch PARP off; they trap it on the DNA, turning a harmless nick into a lethal break when the cell copies its DNA.","route":"/pathways/base-excision-repair-parp/","kind":"pathway","cancerIcon":"glioblastoma","facets":{"kind":["Pathway"],"cancers":["Glioma & glioblastoma","Ovarian cancer","Prostate cancer","Triple-negative breast cancer"],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[{"label":"Glioma & glioblastoma","href":"/cancers/glioblastoma/","tip":"Gliomas are now diagnosed by molecular class, and three classes got their first targeted drugs in 2024-25 (vorasidenib for IDH-mutant glioma, tovorafenib for BRAF-altered paediatric glioma, dordaviprone for H3 K27M). Glioblastoma itself is the hardest to treat and has kept the same standard since 2005; CAR-T delivered into the brain and focused-ultrasound drug delivery are the live directions."},{"label":"Ovarian cancer","href":"/cancers/ovarian/","tip":"Usually found late. PARP inhibitors transformed maintenance therapy, and ADCs against folate receptor and CDH6 are arriving for platinum-resistant disease."},{"label":"Prostate cancer","href":"/cancers/prostate/","tip":"Prostate cancer is the home of theranostics: PSMA PET finds it, PSMA radioligands treat it. Hormonal therapy remains the foundation, with PARP and AKT inhibitors added by genotype."},{"label":"Triple-negative breast cancer","href":"/cancers/tnbc/","tip":"A breast cancer that lacks the three receptors (oestrogen, progesterone, HER2) that other breast cancers can be treated through. It was the hardest subtype for decades; since 2020 immunotherapy and ADCs have changed that."}],"tags":[{"label":"mechanics-atlas","href":"/tagged/mechanics-atlas/","tip":"Every record tagged mechanics-atlas."}]},"sortKeys":{"year":0}},{"id":"basement-membrane-tissue-barriers","name":"Basement membrane & tissue barriers","tldr":"Every organ keeps its lining cells behind a thin, dense sheet of protein called the basement membrane. A tumour that has not crossed it is 'in situ' and essentially curable; crossing it is the moment cancer becomes invasive.","route":"/pathways/basement-membrane-tissue-barriers/","kind":"pathway","cancerIcon":"cervical","facets":{"kind":["Pathway"],"cancers":["Cervical cancer","Oesophageal cancer","HR-positive / HER2-negative breast cancer","Bladder & urothelial cancer"],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[{"label":"Cervical cancer","href":"/cancers/cervical/","tip":"A cancer that could be eliminated by HPV vaccination and screening. For those who develop it, immunotherapy and a tissue-factor ADC have improved survival."},{"label":"Oesophageal cancer","href":"/cancers/esophageal/","tip":"Oesophageal cancer is really two diseases sharing one organ: squamous cell carcinoma, which dominates in Asia, and adenocarcinoma, which dominates in the West and is treated like gastric cancer. Immunotherapy is now standard, and the bispecific ADC iza-bren posted a positive phase 3 in the squamous type in 2026."},{"label":"HR-positive / HER2-negative breast cancer","href":"/cancers/breast-hr-positive/","tip":"HR-positive breast cancer is the most common breast cancer, driven by oestrogen. It was treated for years with hormone-blocking pills, now joined by CDK4/6 inhibitors, PI3K-pathway drugs, degraders, and ADCs."},{"label":"Bladder & urothelial cancer","href":"/cancers/urothelial/","tip":"Bladder cancer went from 40 years of cisplatin to an ADC-immunotherapy combination that nearly doubled survival, and in 2026 the first blood-test-guided drug approval."}],"tags":[{"label":"mechanics-atlas","href":"/tagged/mechanics-atlas/","tip":"Every record tagged mechanics-atlas."}]},"sortKeys":{"year":0}},{"id":"idea-drugging-myc","name":"Can MYC be drugged directly, and will patients tolerate it?","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.","route":"/ideas/idea-drugging-myc/","kind":"idea","cancerIcon":"pancreatic","facets":{"kind":["Idea"],"cancers":["Pancreatic ductal adenocarcinoma","Triple-negative breast cancer","Neuroblastoma"],"year":[]},"cols":{"kind":{"facet":"kind","value":"Idea","tip":"Hypotheses and new directions, linked to the evidence."},"cancers":[{"label":"Pancreatic ductal adenocarcinoma","href":"/cancers/pancreatic/","tip":"Almost every pancreatic tumour carries a KRAS mutation, and for the first time drugs against it work: daraxonrasib nearly doubled survival in previously treated disease in 2026. Pancreatic cancer has been the hardest common cancer to treat once advanced; that is what is starting to change."},{"label":"Triple-negative breast cancer","href":"/cancers/tnbc/","tip":"A breast cancer that lacks the three receptors (oestrogen, progesterone, HER2) that other breast cancers can be treated through. It was the hardest subtype for decades; since 2020 immunotherapy and ADCs have changed that."},{"label":"Neuroblastoma","href":"/cancers/neuroblastoma/","tip":"Neuroblastoma is a childhood nerve-cell cancer where anti-GD2 antibodies and, recently, GD2 CAR-T have improved survival in high-risk disease."}],"tags":[{"label":"open-question","href":"/tagged/open-question/","tip":"Every record tagged open-question."}]},"sortKeys":{"year":0}},{"id":"cachexia-biology","name":"Cancer cachexia","tldr":"The wasting syndrome that kills up to a third of cancer patients: tumours send hormonal signals (GDF-15, IL-6) that switch off appetite and burn muscle and fat. The first drug to reverse it, ponsegromab, showed weight gain in 2024.","route":"/pathways/cachexia-biology/","kind":"pathway","cancerIcon":"pancreatic","facets":{"kind":["Pathway"],"cancers":["Pancreatic ductal adenocarcinoma","Non-small-cell lung cancer","Gastric & gastro-oesophageal junction cancer"],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[{"label":"Pancreatic ductal adenocarcinoma","href":"/cancers/pancreatic/","tip":"Almost every pancreatic tumour carries a KRAS mutation, and for the first time drugs against it work: daraxonrasib nearly doubled survival in previously treated disease in 2026. Pancreatic cancer has been the hardest common cancer to treat once advanced; that is what is starting to change."},{"label":"Non-small-cell lung cancer","href":"/cancers/nsclc/","tip":"Non-small-cell lung cancer is the proving ground for precision medicine: a dozen targetable mutations each with a matched pill, immunotherapy for the rest, and ADCs and bispecifics arriving now. Because most cases are still found late, low-dose CT screening is the other half of the story."},{"label":"Gastric & gastro-oesophageal junction cancer","href":"/cancers/gastric/","tip":"A cancer with three new targets in five years: Claudin 18.2, FGFR2b, and HER2 with new ADCs, plus immunotherapy in first line."}],"tags":[]},"sortKeys":{"year":0}},{"id":"cancer-metabolism","name":"Cancer metabolism","tldr":"Cancer cells rewire how they eat. They burn glucose inefficiently but fast (the Warburg effect), gorge on glutamine and fats, and build the nucleotides and lipids needed to divide. This is why the FDG PET scan works, and why metabolism is a drug target.","route":"/pathways/cancer-metabolism/","kind":"pathway","schematic":{"id":"fdg-pet","sections":["imaging"]},"facets":{"kind":["Pathway"],"cancers":[],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[],"tags":[]},"sortKeys":{"year":0}},{"id":"cancer-neuroscience","name":"Cancer neuroscience (nerve-tumour signalling)","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.","route":"/pathways/cancer-neuroscience/","kind":"pathway","cancerIcon":"pancreatic","facets":{"kind":["Pathway"],"cancers":["Pancreatic ductal adenocarcinoma","Prostate cancer","Glioma & glioblastoma","Head and neck squamous cell carcinoma","Melanoma"],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[{"label":"Pancreatic ductal adenocarcinoma","href":"/cancers/pancreatic/","tip":"Almost every pancreatic tumour carries a KRAS mutation, and for the first time drugs against it work: daraxonrasib nearly doubled survival in previously treated disease in 2026. Pancreatic cancer has been the hardest common cancer to treat once advanced; that is what is starting to change."},{"label":"Prostate cancer","href":"/cancers/prostate/","tip":"Prostate cancer is the home of theranostics: PSMA PET finds it, PSMA radioligands treat it. Hormonal therapy remains the foundation, with PARP and AKT inhibitors added by genotype."},{"label":"Glioma & glioblastoma","href":"/cancers/glioblastoma/","tip":"Gliomas are now diagnosed by molecular class, and three classes got their first targeted drugs in 2024-25 (vorasidenib for IDH-mutant glioma, tovorafenib for BRAF-altered paediatric glioma, dordaviprone for H3 K27M). Glioblastoma itself is the hardest to treat and has kept the same standard since 2005; CAR-T delivered into the brain and focused-ultrasound drug delivery are the live directions."},{"label":"Head and neck squamous cell carcinoma","href":"/cancers/head-and-neck/","tip":"Cancers of the mouth and throat, increasingly caused by HPV. Immunotherapy is first line for advanced disease and now used before surgery."}],"tags":[]},"sortKeys":{"year":0}},{"id":"cancer-stem-cells-plasticity","name":"Cancer stem cells & phenotypic plasticity","tldr":"Some cancer cells behave like stem cells: they can regrow the whole tumour, resist treatment, and switch identities. This plasticity explains why tumours come back and why some lung and prostate cancers transform into a different cancer type under therapy.","route":"/pathways/cancer-stem-cells-plasticity/","kind":"pathway","facets":{"kind":["Pathway"],"cancers":[],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[],"tags":[]},"sortKeys":{"year":0}},{"id":"senescence","name":"Cellular senescence","tldr":"Damaged cells can stop dividing permanently instead of dying. That protects against cancer at first, but senescent cells linger, secrete inflammatory signals, and after chemotherapy can help tumours relapse, so removing them (senolytics) is a new strategy.","route":"/pathways/senescence/","kind":"pathway","schematic":{"id":"cdk46-inhibitor","sections":["targeted-therapy","hormonal"]},"facets":{"kind":["Pathway"],"cancers":[],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[],"tags":[]},"sortKeys":{"year":0}},{"id":"chromosomal-instability","name":"Chromosomal instability & aneuploidy","tldr":"Most cancers have the wrong number of chromosomes and keep shuffling them at every division. This chaos fuels evolution and drug resistance, but it also stresses the cell and can trigger immune alarms, a double edge that researchers are trying to exploit.","route":"/pathways/chromosomal-instability/","kind":"pathway","schematic":{"id":"wes-wgs","sections":["diagnostics","drug-discovery"]},"facets":{"kind":["Pathway"],"cancers":[],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[],"tags":[]},"sortKeys":{"year":0}},{"id":"circadian-control","name":"Circadian control","tldr":"Cells run on a 24-hour clock that gates cell division, DNA repair, and drug metabolism. Cancers often break their clocks, and the time of day a drug or immunotherapy is given can change how well it works.","route":"/pathways/circadian-control/","kind":"pathway","schematic":{"id":"checkpoint-inhibitor","sections":["immunotherapy"]},"facets":{"kind":["Pathway"],"cancers":[],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[],"tags":[]},"sortKeys":{"year":0}},{"id":"clonal-evolution","name":"Clonal evolution & minimal residual disease","tldr":"A tumour is a population that evolves by natural selection. Treatment kills the sensitive cells and selects the rest, which is why resistance is the rule; measuring the surviving population (MRD) and adapting therapy is the counter-strategy.","route":"/pathways/clonal-evolution/","kind":"pathway","schematic":{"id":"mrd-testing","sections":["diagnostics"]},"facets":{"kind":["Pathway"],"cancers":[],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[],"tags":[]},"sortKeys":{"year":0}},{"id":"clonal-haematopoiesis","name":"Clonal haematopoiesis (CHIP)","tldr":"As we age, blood stem cells with cancer-like mutations quietly expand in most people. These clones raise leukaemia and heart disease risk, are accelerated by chemotherapy, and confuse blood tests for cancer DNA.","route":"/pathways/clonal-haematopoiesis/","kind":"pathway","cancerIcon":"aml","facets":{"kind":["Pathway"],"cancers":["Acute myeloid leukaemia"],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[{"label":"Acute myeloid leukaemia","href":"/cancers/aml/","tip":"Acute myeloid leukaemia is an aggressive blood cancer where, after 40 years of the same chemotherapy, a wave of targeted drugs (FLT3, IDH, BCL-2, menin) arrived."}],"tags":[]},"sortKeys":{"year":0}},{"id":"immune-desert-exclusion","name":"Cold tumours: immune deserts and exclusion","tldr":"Tumours come in three immune weathers: inflamed (T cells inside, checkpoint drugs work), excluded (T cells stuck at the edge), and desert (no T cells at all). Most common cancers are excluded or desert, and turning them 'hot' is the central problem of immunotherapy.","route":"/pathways/immune-desert-exclusion/","kind":"pathway","schematic":{"id":"checkpoint-inhibitor","sections":["immunotherapy"]},"facets":{"kind":["Pathway"],"cancers":[],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[],"tags":[{"label":"mechanics-atlas","href":"/tagged/mechanics-atlas/","tip":"Every record tagged mechanics-atlas."}]},"sortKeys":{"year":0}},{"id":"complement-in-cancer","name":"Complement in cancer","tldr":"Complement is a cascade of blood proteins that punches holes in things marked by antibodies and calls in inflammatory cells. Therapeutic antibodies such as rituximab use it to kill cancer cells; tumours defend themselves with shields (CD46, CD55, CD59), and the cascade's own by-products (C5a) can recruit the myeloid cells that protect the tumour.","route":"/pathways/complement-in-cancer/","kind":"pathway","cancerIcon":"dlbcl","facets":{"kind":["Pathway"],"cancers":["Diffuse large B-cell lymphoma","Follicular lymphoma","Chronic lymphocytic leukaemia","Multiple myeloma"],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[{"label":"Diffuse large B-cell lymphoma","href":"/cancers/dlbcl/","tip":"Diffuse large B-cell lymphoma (DLBCL) is an aggressive but curable lymphoma. CAR-T cures about 40% of relapsed patients, and off-the-shelf bispecifics are now approved."},{"label":"Follicular lymphoma","href":"/cancers/follicular-lymphoma/","tip":"Follicular lymphoma is the most common slow-growing lymphoma, defined in about 85% of cases by a BCL2 translocation. Most people live with it for decades, treated only when it causes problems; it can be controlled repeatedly with anti-CD20 antibodies, chemotherapy, bispecifics or CAR-T but rarely cured, and a small share transform into an aggressive lymphoma each year."},{"label":"Chronic lymphocytic leukaemia","href":"/cancers/cll/","tip":"A slow leukaemia that no longer needs chemotherapy: BTK inhibitors and venetoclax control it for years, often in fixed-duration courses."},{"label":"Multiple myeloma","href":"/cancers/multiple-myeloma/","tip":"Multiple myeloma is a plasma-cell cancer with more new drug classes than any other: proteasome inhibitors, IMiDs, CD38 antibodies, BCMA CAR-T, bispecifics, and an ADC."}],"tags":[{"label":"mechanics-atlas","href":"/tagged/mechanics-atlas/","tip":"Every record tagged mechanics-atlas."}]},"sortKeys":{"year":0}},{"id":"idea-nerve-tumour-blockade","name":"Cut the nerve supply to tumours with old drugs","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.","route":"/ideas/idea-nerve-tumour-blockade/","kind":"idea","cancerIcon":"pancreatic","facets":{"kind":["Idea"],"cancers":["Pancreatic ductal adenocarcinoma","Glioma & glioblastoma","Prostate cancer","Head and neck squamous cell carcinoma"],"year":[]},"cols":{"kind":{"facet":"kind","value":"Idea","tip":"Hypotheses and new directions, linked to the evidence."},"cancers":[{"label":"Pancreatic ductal adenocarcinoma","href":"/cancers/pancreatic/","tip":"Almost every pancreatic tumour carries a KRAS mutation, and for the first time drugs against it work: daraxonrasib nearly doubled survival in previously treated disease in 2026. Pancreatic cancer has been the hardest common cancer to treat once advanced; that is what is starting to change."},{"label":"Glioma & glioblastoma","href":"/cancers/glioblastoma/","tip":"Gliomas are now diagnosed by molecular class, and three classes got their first targeted drugs in 2024-25 (vorasidenib for IDH-mutant glioma, tovorafenib for BRAF-altered paediatric glioma, dordaviprone for H3 K27M). Glioblastoma itself is the hardest to treat and has kept the same standard since 2005; CAR-T delivered into the brain and focused-ultrasound drug delivery are the live directions."},{"label":"Prostate cancer","href":"/cancers/prostate/","tip":"Prostate cancer is the home of theranostics: PSMA PET finds it, PSMA radioligands treat it. Hormonal therapy remains the foundation, with PARP and AKT inhibitors added by genotype."},{"label":"Head and neck squamous cell carcinoma","href":"/cancers/head-and-neck/","tip":"Cancers of the mouth and throat, increasingly caused by HPV. Immunotherapy is first line for advanced disease and now used before surgery."}],"tags":[{"label":"open-question","href":"/tagged/open-question/","tip":"Every record tagged open-question."}]},"sortKeys":{"year":0}},{"id":"dna-replication-licensing","name":"DNA replication & origin licensing","tldr":"Before a cell divides it must copy three billion letters of DNA exactly once, 'licensing' thousands of start points in advance and firing them in waves. Cancers driven by MYC, cyclin E or RAS fire excess start points too fast, and antimetabolites such as 5-FU, topoisomerase poisons such as irinotecan and platinum drugs all jam this copying machinery.","route":"/pathways/dna-replication-licensing/","kind":"pathway","schematic":{"id":"cytotoxic-chemotherapy","sections":["chemotherapy"]},"facets":{"kind":["Pathway"],"cancers":[],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[],"tags":[{"label":"mechanics-atlas","href":"/tagged/mechanics-atlas/","tip":"Every record tagged mechanics-atlas."}]},"sortKeys":{"year":0}},{"id":"replication-stress","name":"DNA replication stress","tldr":"Cancers copy their DNA too fast and with broken checkpoints, so replication forks stall and collapse. They survive only by leaning on emergency repair kinases such as ATR, CHK1, and WEE1, which is why blocking those kinases can be selectively lethal.","route":"/pathways/replication-stress/","kind":"pathway","schematic":{"id":"synthetic-lethality-approaches","sections":["targeted-therapy","drug-discovery"]},"facets":{"kind":["Pathway"],"cancers":[],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[],"tags":[]},"sortKeys":{"year":0}},{"id":"homologous-recombination-repair","name":"Double-strand break repair: HR versus end joining","tldr":"A break through both strands of DNA is the most dangerous lesion a cell faces. Two crews compete to fix it: homologous recombination copies the answer from the sister chromosome (accurate, needs BRCA), while end joining simply glues the ends (fast, sloppy). Which crew wins decides whether PARP inhibitors and radiation kill the cell.","route":"/pathways/homologous-recombination-repair/","kind":"pathway","cancerIcon":"ovarian","facets":{"kind":["Pathway"],"cancers":["Ovarian cancer","Triple-negative breast cancer","Prostate cancer","Pancreatic ductal adenocarcinoma"],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[{"label":"Ovarian cancer","href":"/cancers/ovarian/","tip":"Usually found late. PARP inhibitors transformed maintenance therapy, and ADCs against folate receptor and CDH6 are arriving for platinum-resistant disease."},{"label":"Triple-negative breast cancer","href":"/cancers/tnbc/","tip":"A breast cancer that lacks the three receptors (oestrogen, progesterone, HER2) that other breast cancers can be treated through. It was the hardest subtype for decades; since 2020 immunotherapy and ADCs have changed that."},{"label":"Prostate cancer","href":"/cancers/prostate/","tip":"Prostate cancer is the home of theranostics: PSMA PET finds it, PSMA radioligands treat it. Hormonal therapy remains the foundation, with PARP and AKT inhibitors added by genotype."},{"label":"Pancreatic ductal adenocarcinoma","href":"/cancers/pancreatic/","tip":"Almost every pancreatic tumour carries a KRAS mutation, and for the first time drugs against it work: daraxonrasib nearly doubled survival in previously treated disease in 2026. Pancreatic cancer has been the hardest common cancer to treat once advanced; that is what is starting to change."}],"tags":[{"label":"mechanics-atlas","href":"/tagged/mechanics-atlas/","tip":"Every record tagged mechanics-atlas."}]},"sortKeys":{"year":0}},{"id":"oncogene-activation-two-hit","name":"Drivers, passengers & the two-hit model","tldr":"Of the thousands of mutations in a tumour, only a handful (typically 2-8) actually drive it. Drivers either jam an accelerator on (oncogenes, one hit is enough) or remove a brake (tumour suppressors, both copies must go). Everything else is a passenger along for the ride.","route":"/pathways/oncogene-activation-two-hit/","kind":"pathway","cancerIcon":"retinoblastoma","facets":{"kind":["Pathway"],"cancers":["Retinoblastoma","Colorectal cancer","Chronic myeloid leukaemia"],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[{"label":"Retinoblastoma","href":"/cancers/retinoblastoma/","tip":"An eye cancer of infants caused by loss of the RB1 gene, the first tumour-suppressor gene ever found. In rich countries almost every child survives and most eyes are saved by chemotherapy delivered through the eye's artery; in low-income countries, where most cases occur, survival depends on finding it early, and that is the global gap."},{"label":"Colorectal cancer","href":"/cancers/colorectal/","tip":"The cancer where screening works best and where immunotherapy can make some tumours disappear entirely, yet most metastatic disease still depends on chemotherapy."},{"label":"Chronic myeloid leukaemia","href":"/cancers/cml/","tip":"Chronic myeloid leukaemia is a blood cancer driven by a single fused gene, BCR-ABL1, and the model for oncogene-targeted treatment: imatinib in 2001 and the tyrosine kinase inhibitors that followed turned it into a condition most people live with long-term. About half of patients with a sustained deep molecular response can now stop treatment altogether."}],"tags":[{"label":"mechanics-atlas","href":"/tagged/mechanics-atlas/","tip":"Every record tagged mechanics-atlas."}]},"sortKeys":{"year":0}},{"id":"drug-efflux-pumps","name":"Drug efflux pumps (ABC transporters)","tldr":"Cancer cells can install pumps in their outer membrane that throw chemotherapy back out as fast as it comes in. The same pumps guard the gut, brain and bone marrow in healthy tissue, which is why blocking them failed as a strategy and why drug designers now choose payloads the pumps cannot grip.","route":"/pathways/drug-efflux-pumps/","kind":"pathway","schematic":{"id":"adc","sections":["adcs"]},"facets":{"kind":["Pathway"],"cancers":[],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[],"tags":[{"label":"mechanics-atlas","href":"/tagged/mechanics-atlas/","tip":"Every record tagged mechanics-atlas."}]},"sortKeys":{"year":0}},{"id":"drug-tolerant-persisters","name":"Drug-tolerant persister cells","tldr":"Even when a drug wipes out 99% of a tumour, a few cells survive without any resistance mutation: they go quiet, stop dividing, and wait. These persisters are the seed of relapse. They are hard to kill precisely because they are not doing much, but they have their own weaknesses.","route":"/pathways/drug-tolerant-persisters/","kind":"pathway","schematic":{"id":"mrd-testing","sections":["diagnostics"]},"facets":{"kind":["Pathway"],"cancers":[],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[],"tags":[{"label":"mechanics-atlas","href":"/tagged/mechanics-atlas/","tip":"Every record tagged mechanics-atlas."}]},"sortKeys":{"year":0}},{"id":"epigenetic-reprogramming","name":"Epigenetic reprogramming","tldr":"Cancer changes not just its genes but how they are read: chemical tags on DNA and histones silence guardians and awaken growth programmes. Unlike mutations, these changes are reversible, which is the hope behind epigenetic drugs.","route":"/pathways/epigenetic-reprogramming/","kind":"pathway","schematic":{"id":"epigenetic-drugs","sections":["epigenetics"]},"facets":{"kind":["Pathway"],"cancers":[],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[],"tags":[]},"sortKeys":{"year":0}},{"id":"extrinsic-apoptosis-death-receptors","name":"Extrinsic apoptosis (death receptors)","tldr":"Immune cells kill by touch: they present FAS ligand or TRAIL to a target cell, whose death receptors then trigger self-destruction from the outside in. Tumours cut this wire by deleting the receptors or over-producing decoys and blockers.","route":"/pathways/extrinsic-apoptosis-death-receptors/","kind":"pathway","schematic":{"id":"car-t","sections":["cell-therapy"]},"facets":{"kind":["Pathway"],"cancers":[],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[],"tags":[{"label":"mechanics-atlas","href":"/tagged/mechanics-atlas/","tip":"Every record tagged mechanics-atlas."}]},"sortKeys":{"year":0}},{"id":"ferroptosis-cell-death","name":"Ferroptosis & regulated cell death","tldr":"Cells can die in several programmed ways. Beyond the classic apoptosis, ferroptosis kills through iron-driven fat oxidation, and drug-resistant, mesenchymal cancer cells turn out to be unusually prone to it.","route":"/pathways/ferroptosis-cell-death/","kind":"pathway","facets":{"kind":["Pathway"],"cancers":[],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[],"tags":[]},"sortKeys":{"year":0}},{"id":"caf-activation-desmoplasia","name":"Fibroblast activation, desmoplasia & matrix stiffness","tldr":"Tumours recruit the body's repair cells, fibroblasts, and keep them in wound-healing mode forever. The scar tissue they lay down (desmoplasia) squeezes blood vessels shut, walls out immune cells, stiffens the tissue in a way that itself tells cancer cells to grow, and is why pancreatic cancer is so hard to treat.","route":"/pathways/caf-activation-desmoplasia/","kind":"pathway","cancerIcon":"pancreatic","facets":{"kind":["Pathway"],"cancers":["Pancreatic ductal adenocarcinoma","Biliary tract cancer","HR-positive / HER2-negative breast cancer"],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[{"label":"Pancreatic ductal adenocarcinoma","href":"/cancers/pancreatic/","tip":"Almost every pancreatic tumour carries a KRAS mutation, and for the first time drugs against it work: daraxonrasib nearly doubled survival in previously treated disease in 2026. Pancreatic cancer has been the hardest common cancer to treat once advanced; that is what is starting to change."},{"label":"Biliary tract cancer","href":"/cancers/cholangiocarcinoma/","tip":"Cholangiocarcinoma is cancer of the bile ducts or gallbladder. It is rare and often found late, but it turned out to carry more targetable mutations than almost any other gastrointestinal cancer, and immunotherapy now adds to chemotherapy from the first treatment."},{"label":"HR-positive / HER2-negative breast cancer","href":"/cancers/breast-hr-positive/","tip":"HR-positive breast cancer is the most common breast cancer, driven by oestrogen. It was treated for years with hormone-blocking pills, now joined by CDK4/6 inhibitors, PI3K-pathway drugs, degraders, and ADCs."}],"tags":[{"label":"mechanics-atlas","href":"/tagged/mechanics-atlas/","tip":"Every record tagged mechanics-atlas."}]},"sortKeys":{"year":0}},{"id":"field-cancerisation","name":"Field cancerisation","tldr":"Cancer often arises from a whole region of tissue that already carries mutations, not from one rogue cell. Sun-exposed skin, smokers' airways, and Barrett's oesophagus are patchworks of mutant clones competing long before a tumour appears.","route":"/pathways/field-cancerisation/","kind":"pathway","cancerIcon":"esophageal","facets":{"kind":["Pathway"],"cancers":["Oesophageal cancer","Head and neck squamous cell carcinoma","Non-small-cell lung cancer","Cervical cancer","Colorectal cancer"],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[{"label":"Oesophageal cancer","href":"/cancers/esophageal/","tip":"Oesophageal cancer is really two diseases sharing one organ: squamous cell carcinoma, which dominates in Asia, and adenocarcinoma, which dominates in the West and is treated like gastric cancer. Immunotherapy is now standard, and the bispecific ADC iza-bren posted a positive phase 3 in the squamous type in 2026."},{"label":"Head and neck squamous cell carcinoma","href":"/cancers/head-and-neck/","tip":"Cancers of the mouth and throat, increasingly caused by HPV. Immunotherapy is first line for advanced disease and now used before surgery."},{"label":"Non-small-cell lung cancer","href":"/cancers/nsclc/","tip":"Non-small-cell lung cancer is the proving ground for precision medicine: a dozen targetable mutations each with a matched pill, immunotherapy for the rest, and ADCs and bispecifics arriving now. Because most cases are still found late, low-dose CT screening is the other half of the story."},{"label":"Cervical cancer","href":"/cancers/cervical/","tip":"A cancer that could be eliminated by HPV vaccination and screening. For those who develop it, immunotherapy and a tissue-factor ADC have improved survival."}],"tags":[]},"sortKeys":{"year":0}},{"id":"idea-chronotherapy-immunotherapy","name":"Give immunotherapy in the morning","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.","route":"/ideas/idea-chronotherapy-immunotherapy/","kind":"idea","cancerIcon":"nsclc","facets":{"kind":["Idea"],"cancers":["Non-small-cell lung cancer","Melanoma"],"year":[]},"cols":{"kind":{"facet":"kind","value":"Idea","tip":"Hypotheses and new directions, linked to the evidence."},"cancers":[{"label":"Non-small-cell lung cancer","href":"/cancers/nsclc/","tip":"Non-small-cell lung cancer is the proving ground for precision medicine: a dozen targetable mutations each with a matched pill, immunotherapy for the rest, and ADCs and bispecifics arriving now. Because most cases are still found late, low-dose CT screening is the other half of the story."},{"label":"Melanoma","href":"/cancers/melanoma/","tip":"The skin cancer that proved immunotherapy works: half of advanced patients now live 10 years. Also the first with an approved TIL therapy, an oncolytic virus, and a positive phase 3 personalised vaccine."}],"tags":[{"label":"open-question","href":"/tagged/open-question/","tip":"Every record tagged open-question."}]},"sortKeys":{"year":0}},{"id":"glutamine-metabolism","name":"Glutamine addiction","tldr":"After glucose, glutamine is the tumour's favourite food. It feeds the energy cycle, donates nitrogen for making DNA letters, and makes the antioxidant glutathione. MYC- and KRAS-driven cancers eat so much of it that they starve the T cells next door.","route":"/pathways/glutamine-metabolism/","kind":"pathway","cancerIcon":"all-leukemia","facets":{"kind":["Pathway"],"cancers":["Acute lymphoblastic leukaemia","Renal cell carcinoma","Pancreatic ductal adenocarcinoma","Glioma & glioblastoma"],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[{"label":"Acute lymphoblastic leukaemia","href":"/cancers/all-leukemia/","tip":"Acute lymphoblastic leukaemia is the childhood cancer success story, and was the first disease treated with CAR-T and with a T-cell engager."},{"label":"Renal cell carcinoma","href":"/cancers/rcc/","tip":"Kidney cancer is where anti-angiogenic drugs and immunotherapy came together, and where a Nobel-winning oxygen-sensing pathway yielded a drug, belzutifan."},{"label":"Pancreatic ductal adenocarcinoma","href":"/cancers/pancreatic/","tip":"Almost every pancreatic tumour carries a KRAS mutation, and for the first time drugs against it work: daraxonrasib nearly doubled survival in previously treated disease in 2026. Pancreatic cancer has been the hardest common cancer to treat once advanced; that is what is starting to change."},{"label":"Glioma & glioblastoma","href":"/cancers/glioblastoma/","tip":"Gliomas are now diagnosed by molecular class, and three classes got their first targeted drugs in 2024-25 (vorasidenib for IDH-mutant glioma, tovorafenib for BRAF-altered paediatric glioma, dordaviprone for H3 K27M). Glioblastoma itself is the hardest to treat and has kept the same standard since 2005; CAR-T delivered into the brain and focused-ultrasound drug delivery are the live directions."}],"tags":[{"label":"mechanics-atlas","href":"/tagged/mechanics-atlas/","tip":"Every record tagged mechanics-atlas."}]},"sortKeys":{"year":0}},{"id":"hedgehog","name":"Hedgehog signalling","tldr":"A developmental pathway that shapes embryos and is switched back on in basal cell skin cancer and some brain tumours. Blocking it cures most advanced basal cell carcinomas, but tumours learn to reactivate it downstream.","route":"/pathways/hedgehog/","kind":"pathway","cancerIcon":"glioblastoma","facets":{"kind":["Pathway"],"cancers":["Glioma & glioblastoma","Acute myeloid leukaemia"],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[{"label":"Glioma & glioblastoma","href":"/cancers/glioblastoma/","tip":"Gliomas are now diagnosed by molecular class, and three classes got their first targeted drugs in 2024-25 (vorasidenib for IDH-mutant glioma, tovorafenib for BRAF-altered paediatric glioma, dordaviprone for H3 K27M). Glioblastoma itself is the hardest to treat and has kept the same standard since 2005; CAR-T delivered into the brain and focused-ultrasound drug delivery are the live directions."},{"label":"Acute myeloid leukaemia","href":"/cancers/aml/","tip":"Acute myeloid leukaemia is an aggressive blood cancer where, after 40 years of the same chemotherapy, a wave of targeted drugs (FLT3, IDH, BCL-2, menin) arrived."}],"tags":[]},"sortKeys":{"year":0}},{"id":"hippo-yap","name":"Hippo-YAP/TAZ","tldr":"The pathway that tells organs when to stop growing. Cancers disable it so YAP and TAZ stay in the nucleus driving growth; in mesothelioma, NF2 loss does exactly that, and the first drugs against the YAP-TEAD switch are in trials.","route":"/pathways/hippo-yap/","kind":"pathway","cancerIcon":"mesothelioma","facets":{"kind":["Pathway"],"cancers":["Mesothelioma"],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[{"label":"Mesothelioma","href":"/cancers/mesothelioma/","tip":"An asbestos-caused cancer of the lung lining. Immunotherapy doublets replaced chemotherapy in 2020, and mesothelin CAR-T is under study."}],"tags":[]},"sortKeys":{"year":0}},{"id":"inflammation-nfkb","name":"Inflammation & NF-κB","tldr":"Chronic inflammation is soil for cancer: it feeds growth signals, DNA damage, and immune suppression. The NF-κB switch inside cells is the master relay, and colitis, hepatitis, and H. pylori gastritis are the clinical proof.","route":"/pathways/inflammation-nfkb/","kind":"pathway","schematic":{"id":"chemoprevention","sections":["prevention"]},"facets":{"kind":["Pathway"],"cancers":[],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[],"tags":[]},"sortKeys":{"year":0}},{"id":"idea-field-interception","name":"Intercept cancer at the field stage","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.","route":"/ideas/idea-field-interception/","kind":"idea","cancerIcon":"esophageal","facets":{"kind":["Idea"],"cancers":["Oesophageal cancer","Non-small-cell lung cancer","Head and neck squamous cell carcinoma"],"year":[]},"cols":{"kind":{"facet":"kind","value":"Idea","tip":"Hypotheses and new directions, linked to the evidence."},"cancers":[{"label":"Oesophageal cancer","href":"/cancers/esophageal/","tip":"Oesophageal cancer is really two diseases sharing one organ: squamous cell carcinoma, which dominates in Asia, and adenocarcinoma, which dominates in the West and is treated like gastric cancer. Immunotherapy is now standard, and the bispecific ADC iza-bren posted a positive phase 3 in the squamous type in 2026."},{"label":"Non-small-cell lung cancer","href":"/cancers/nsclc/","tip":"Non-small-cell lung cancer is the proving ground for precision medicine: a dozen targetable mutations each with a matched pill, immunotherapy for the rest, and ADCs and bispecifics arriving now. Because most cases are still found late, low-dose CT screening is the other half of the story."},{"label":"Head and neck squamous cell carcinoma","href":"/cancers/head-and-neck/","tip":"Cancers of the mouth and throat, increasingly caused by HPV. Immunotherapy is first line for advanced disease and now used before surgery."}],"tags":[{"label":"open-question","href":"/tagged/open-question/","tip":"Every record tagged open-question."}]},"sortKeys":{"year":0}},{"id":"intravasation-ctc-survival","name":"Intravasation & circulating tumour cells","tldr":"Getting into the bloodstream and surviving there is brutal: cells are ripped from their neighbours, battered by flow, and hunted by NK cells. Fewer than one in a thousand survive. The ones that do travel in clusters, wear a cloak of platelets, or ride with neutrophils. Liquid biopsies catch what is left.","route":"/pathways/intravasation-ctc-survival/","kind":"pathway","schematic":{"id":"liquid-biopsy","sections":["diagnostics"]},"facets":{"kind":["Pathway"],"cancers":[],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[],"tags":[{"label":"mechanics-atlas","href":"/tagged/mechanics-atlas/","tip":"Every record tagged mechanics-atlas."}]},"sortKeys":{"year":0}},{"id":"invasion-ecm-degradation","name":"Invasion: proteases, adhesion & the invasive front","tldr":"To invade, a cancer cell must grip the scaffolding around it, dissolve a path with enzymes, and pull itself forward, alone or in a chain led by a scout cell. Fibroblasts often cut the trail first. The enzyme blockers of the 1990s failed; today's targets are the grip (integrins, FAK) and the trail-makers.","route":"/pathways/invasion-ecm-degradation/","kind":"pathway","cancerIcon":"lgsoc","facets":{"kind":["Pathway"],"cancers":["Low-grade serous ovarian cancer","Pancreatic ductal adenocarcinoma","Head and neck squamous cell carcinoma"],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[{"label":"Low-grade serous ovarian cancer","href":"/terms/lgsoc/","tip":"Low-grade serous ovarian cancer is a slow-growing, RAS-driven type of ovarian cancer that resists chemotherapy but responds to hormone blockers and MEK-pathway drugs."},{"label":"Pancreatic ductal adenocarcinoma","href":"/cancers/pancreatic/","tip":"Almost every pancreatic tumour carries a KRAS mutation, and for the first time drugs against it work: daraxonrasib nearly doubled survival in previously treated disease in 2026. Pancreatic cancer has been the hardest common cancer to treat once advanced; that is what is starting to change."},{"label":"Head and neck squamous cell carcinoma","href":"/cancers/head-and-neck/","tip":"Cancers of the mouth and throat, increasingly caused by HPV. Immunotherapy is first line for advanced disease and now used before surgery."}],"tags":[{"label":"mechanics-atlas","href":"/tagged/mechanics-atlas/","tip":"Every record tagged mechanics-atlas."}]},"sortKeys":{"year":0}},{"id":"idea-targeting-aneuploidy","name":"Is aneuploidy itself a druggable vulnerability?","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.","route":"/ideas/idea-targeting-aneuploidy/","kind":"idea","cancerIcon":"ovarian","facets":{"kind":["Idea"],"cancers":["Ovarian cancer","Triple-negative breast cancer"],"year":[]},"cols":{"kind":{"facet":"kind","value":"Idea","tip":"Hypotheses and new directions, linked to the evidence."},"cancers":[{"label":"Ovarian cancer","href":"/cancers/ovarian/","tip":"Usually found late. PARP inhibitors transformed maintenance therapy, and ADCs against folate receptor and CDH6 are arriving for platinum-resistant disease."},{"label":"Triple-negative breast cancer","href":"/cancers/tnbc/","tip":"A breast cancer that lacks the three receptors (oestrogen, progesterone, HER2) that other breast cancers can be treated through. It was the hardest subtype for decades; since 2020 immunotherapy and ADCs have changed that."}],"tags":[{"label":"open-question","href":"/tagged/open-question/","tip":"Every record tagged open-question."}]},"sortKeys":{"year":0}},{"id":"jak-stat","name":"JAK-STAT signalling","tldr":"The relay that turns cytokine signals into gene changes. Overactive in blood cancers (JAK2 in myelofibrosis), it is also the wire that carries interferon's cancer-killing message, so tumours cut it to escape immunotherapy.","route":"/pathways/jak-stat/","kind":"pathway","facets":{"kind":["Pathway"],"cancers":[],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[],"tags":[]},"sortKeys":{"year":0}},{"id":"keap1-nrf2","name":"KEAP1-NRF2 antioxidant pathway","tldr":"KEAP1-NRF2 is the cell's antioxidant defence switch. Lung cancers often break the off-switch (KEAP1), leaving NRF2 permanently on, which detoxifies chemotherapy and radiation and makes these tumours resistant to almost everything.","route":"/pathways/keap1-nrf2/","kind":"pathway","cancerIcon":"nsclc","facets":{"kind":["Pathway"],"cancers":["Non-small-cell lung cancer"],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[{"label":"Non-small-cell lung cancer","href":"/cancers/nsclc/","tip":"Non-small-cell lung cancer is the proving ground for precision medicine: a dozen targetable mutations each with a matched pill, immunotherapy for the rest, and ADCs and bispecifics arriving now. Because most cases are still found late, low-dose CT screening is the other half of the story."}],"tags":[]},"sortKeys":{"year":0}},{"id":"idea-dormancy-maintenance-therapy","name":"Keep them asleep: dormancy maintenance as adjuvant therapy","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.","route":"/ideas/idea-dormancy-maintenance-therapy/","kind":"idea","cancerIcon":"prostate","facets":{"kind":["Idea"],"cancers":["Prostate cancer","HR-positive / HER2-negative breast cancer"],"year":[]},"cols":{"kind":{"facet":"kind","value":"Idea","tip":"Hypotheses and new directions, linked to the evidence."},"cancers":[{"label":"Prostate cancer","href":"/cancers/prostate/","tip":"Prostate cancer is the home of theranostics: PSMA PET finds it, PSMA radioligands treat it. Hormonal therapy remains the foundation, with PARP and AKT inhibitors added by genotype."},{"label":"HR-positive / HER2-negative breast cancer","href":"/cancers/breast-hr-positive/","tip":"HR-positive breast cancer is the most common breast cancer, driven by oestrogen. It was treated for years with hormone-blocking pills, now joined by CDK4/6 inhibitors, PI3K-pathway drugs, degraders, and ADCs."}],"tags":[{"label":"open-question","href":"/tagged/open-question/","tip":"Every record tagged open-question."}]},"sortKeys":{"year":0}},{"id":"idea-ferroptosis-persisters","name":"Kill drug-tolerant persisters through ferroptosis","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.","route":"/ideas/idea-ferroptosis-persisters/","kind":"idea","cancerIcon":"nsclc","facets":{"kind":["Idea"],"cancers":["Non-small-cell lung cancer","Melanoma"],"year":[]},"cols":{"kind":{"facet":"kind","value":"Idea","tip":"Hypotheses and new directions, linked to the evidence."},"cancers":[{"label":"Non-small-cell lung cancer","href":"/cancers/nsclc/","tip":"Non-small-cell lung cancer is the proving ground for precision medicine: a dozen targetable mutations each with a matched pill, immunotherapy for the rest, and ADCs and bispecifics arriving now. Because most cases are still found late, low-dose CT screening is the other half of the story."},{"label":"Melanoma","href":"/cancers/melanoma/","tip":"The skin cancer that proved immunotherapy works: half of advanced patients now live 10 years. Also the first with an approved TIL therapy, an oncolytic virus, and a positive phase 3 personalised vaccine."}],"tags":[{"label":"open-question","href":"/tagged/open-question/","tip":"Every record tagged open-question."}]},"sortKeys":{"year":0}},{"id":"lineage-plasticity-neuroendocrine","name":"Lineage plasticity & neuroendocrine transformation","tldr":"Under pressure from a drug that blocks its identity (the androgen receptor in prostate cancer, EGFR in lung cancer), a tumour can change what kind of cell it is, becoming a small-cell neuroendocrine cancer that no longer needs the blocked signal. It is the ultimate escape: not a new mutation in the engine, but a new engine.","route":"/pathways/lineage-plasticity-neuroendocrine/","kind":"pathway","cancerIcon":"prostate","facets":{"kind":["Pathway"],"cancers":["Prostate cancer","Non-small-cell lung cancer","Small-cell lung cancer","Melanoma"],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[{"label":"Prostate cancer","href":"/cancers/prostate/","tip":"Prostate cancer is the home of theranostics: PSMA PET finds it, PSMA radioligands treat it. Hormonal therapy remains the foundation, with PARP and AKT inhibitors added by genotype."},{"label":"Non-small-cell lung cancer","href":"/cancers/nsclc/","tip":"Non-small-cell lung cancer is the proving ground for precision medicine: a dozen targetable mutations each with a matched pill, immunotherapy for the rest, and ADCs and bispecifics arriving now. Because most cases are still found late, low-dose CT screening is the other half of the story."},{"label":"Small-cell lung cancer","href":"/cancers/sclc/","tip":"A fast-growing lung cancer that responds to chemotherapy then relapses quickly. After 30 years without progress, T-cell engagers and ADCs are finally moving the needle."},{"label":"Melanoma","href":"/cancers/melanoma/","tip":"The skin cancer that proved immunotherapy works: half of advanced patients now live 10 years. Also the first with an approved TIL therapy, an oncolytic virus, and a positive phase 3 personalised vaccine."}],"tags":[{"label":"mechanics-atlas","href":"/tagged/mechanics-atlas/","tip":"Every record tagged mechanics-atlas."}]},"sortKeys":{"year":0}},{"id":"lipid-metabolism-cancer","name":"Lipid synthesis, uptake & cholesterol","tldr":"Dividing cells need membranes, and membranes are fat. Cancers switch on the fat-building enzymes most adult tissues keep off, and in fatty environments (breast, omentum, bone marrow) they also steal lipids from neighbouring fat cells. This links obesity to cancer and offers new drug targets.","route":"/pathways/lipid-metabolism-cancer/","kind":"pathway","cancerIcon":"ovarian","facets":{"kind":["Pathway"],"cancers":["Ovarian cancer","Prostate cancer","HR-positive / HER2-negative breast cancer","Endometrial cancer","Hepatocellular carcinoma"],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[{"label":"Ovarian cancer","href":"/cancers/ovarian/","tip":"Usually found late. PARP inhibitors transformed maintenance therapy, and ADCs against folate receptor and CDH6 are arriving for platinum-resistant disease."},{"label":"Prostate cancer","href":"/cancers/prostate/","tip":"Prostate cancer is the home of theranostics: PSMA PET finds it, PSMA radioligands treat it. Hormonal therapy remains the foundation, with PARP and AKT inhibitors added by genotype."},{"label":"HR-positive / HER2-negative breast cancer","href":"/cancers/breast-hr-positive/","tip":"HR-positive breast cancer is the most common breast cancer, driven by oestrogen. It was treated for years with hormone-blocking pills, now joined by CDK4/6 inhibitors, PI3K-pathway drugs, degraders, and ADCs."},{"label":"Endometrial cancer","href":"/cancers/endometrial/","tip":"The gynaecological cancer where immunotherapy has had the biggest impact, guided by molecular classification."}],"tags":[{"label":"mechanics-atlas","href":"/tagged/mechanics-atlas/","tip":"Every record tagged mechanics-atlas."}]},"sortKeys":{"year":0}},{"id":"idea-metabolic-vulnerability-mapping","name":"Map metabolic dependencies in the patient, not the dish","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.","route":"/ideas/idea-metabolic-vulnerability-mapping/","kind":"idea","cancerIcon":"nsclc","facets":{"kind":["Idea"],"cancers":["Non-small-cell lung cancer","Renal cell carcinoma","Glioma & glioblastoma"],"year":[]},"cols":{"kind":{"facet":"kind","value":"Idea","tip":"Hypotheses and new directions, linked to the evidence."},"cancers":[{"label":"Non-small-cell lung cancer","href":"/cancers/nsclc/","tip":"Non-small-cell lung cancer is the proving ground for precision medicine: a dozen targetable mutations each with a matched pill, immunotherapy for the rest, and ADCs and bispecifics arriving now. Because most cases are still found late, low-dose CT screening is the other half of the story."},{"label":"Renal cell carcinoma","href":"/cancers/rcc/","tip":"Kidney cancer is where anti-angiogenic drugs and immunotherapy came together, and where a Nobel-winning oxygen-sensing pathway yielded a drug, belzutifan."},{"label":"Glioma & glioblastoma","href":"/cancers/glioblastoma/","tip":"Gliomas are now diagnosed by molecular class, and three classes got their first targeted drugs in 2024-25 (vorasidenib for IDH-mutant glioma, tovorafenib for BRAF-altered paediatric glioma, dordaviprone for H3 K27M). Glioblastoma itself is the hardest to treat and has kept the same standard since 2005; CAR-T delivered into the brain and focused-ultrasound drug delivery are the live directions."}],"tags":[{"label":"open-question","href":"/tagged/open-question/","tip":"Every record tagged open-question."}]},"sortKeys":{"year":0}},{"id":"idea-microbiome-io-fmt","name":"Microbiome transplant as a routine immunotherapy adjunct","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.","route":"/ideas/idea-microbiome-io-fmt/","kind":"idea","cancerIcon":"melanoma","facets":{"kind":["Idea"],"cancers":["Melanoma","Non-small-cell lung cancer"],"year":[]},"cols":{"kind":{"facet":"kind","value":"Idea","tip":"Hypotheses and new directions, linked to the evidence."},"cancers":[{"label":"Melanoma","href":"/cancers/melanoma/","tip":"The skin cancer that proved immunotherapy works: half of advanced patients now live 10 years. Also the first with an approved TIL therapy, an oncolytic virus, and a positive phase 3 personalised vaccine."},{"label":"Non-small-cell lung cancer","href":"/cancers/nsclc/","tip":"Non-small-cell lung cancer is the proving ground for precision medicine: a dozen targetable mutations each with a matched pill, immunotherapy for the rest, and ADCs and bispecifics arriving now. Because most cases are still found late, low-dose CT screening is the other half of the story."}],"tags":[{"label":"open-question","href":"/tagged/open-question/","tip":"Every record tagged open-question."}]},"sortKeys":{"year":0}},{"id":"microbiome-tumour","name":"Microbiome-tumour interactions","tldr":"The bacteria in the gut, and even inside tumours, influence whether cancer starts and whether immunotherapy works. Transplanting stool from responders has made some non-responders respond.","route":"/pathways/microbiome-tumour/","kind":"pathway","cancerIcon":"melanoma","facets":{"kind":["Pathway"],"cancers":["Melanoma","Colorectal cancer","Pancreatic ductal adenocarcinoma"],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[{"label":"Melanoma","href":"/cancers/melanoma/","tip":"The skin cancer that proved immunotherapy works: half of advanced patients now live 10 years. Also the first with an approved TIL therapy, an oncolytic virus, and a positive phase 3 personalised vaccine."},{"label":"Colorectal cancer","href":"/cancers/colorectal/","tip":"The cancer where screening works best and where immunotherapy can make some tumours disappear entirely, yet most metastatic disease still depends on chemotherapy."},{"label":"Pancreatic ductal adenocarcinoma","href":"/cancers/pancreatic/","tip":"Almost every pancreatic tumour carries a KRAS mutation, and for the first time drugs against it work: daraxonrasib nearly doubled survival in previously treated disease in 2026. Pancreatic cancer has been the hardest common cancer to treat once advanced; that is what is starting to change."}],"tags":[]},"sortKeys":{"year":0}},{"id":"mismatch-repair-msi","name":"Mismatch repair & microsatellite instability","tldr":"After DNA is copied, a proofreading crew fixes the letters the polymerase got wrong. Lose it and the genome fills with thousands of small errors, especially in repetitive stretches (microsatellites). Those errors make abnormal proteins that the immune system can see, which is why immunotherapy works so well in these cancers.","route":"/pathways/mismatch-repair-msi/","kind":"pathway","cancerIcon":"colorectal","facets":{"kind":["Pathway"],"cancers":["Colorectal cancer","Endometrial cancer","Gastric & gastro-oesophageal junction cancer"],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[{"label":"Colorectal cancer","href":"/cancers/colorectal/","tip":"The cancer where screening works best and where immunotherapy can make some tumours disappear entirely, yet most metastatic disease still depends on chemotherapy."},{"label":"Endometrial cancer","href":"/cancers/endometrial/","tip":"The gynaecological cancer where immunotherapy has had the biggest impact, guided by molecular classification."},{"label":"Gastric & gastro-oesophageal junction cancer","href":"/cancers/gastric/","tip":"A cancer with three new targets in five years: Claudin 18.2, FGFR2b, and HER2 with new ADCs, plus immunotherapy in first line."}],"tags":[{"label":"mechanics-atlas","href":"/tagged/mechanics-atlas/","tip":"Every record tagged mechanics-atlas."}]},"sortKeys":{"year":0}},{"id":"mitotic-spindle-checkpoint","name":"Mitosis & the spindle assembly checkpoint","tldr":"When a cell divides, a scaffold of microtubules (the spindle) pulls one copy of each chromosome to each side. A checkpoint holds the split until every chromosome is hooked on. Taxanes and vinca alkaloids freeze the spindle so the cell is stuck at this checkpoint until it dies.","route":"/pathways/mitotic-spindle-checkpoint/","kind":"pathway","schematic":{"id":"cytotoxic-chemotherapy","sections":["chemotherapy"]},"facets":{"kind":["Pathway"],"cancers":[],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[],"tags":[{"label":"mechanics-atlas","href":"/tagged/mechanics-atlas/","tip":"Every record tagged mechanics-atlas."}]},"sortKeys":{"year":0}},{"id":"mrna-translation-eif4f","name":"mRNA translation (eIF4F / mTOR)","tldr":"Cancer cells must make protein at furious speed. The eIF4F complex that starts protein synthesis is the funnel where growth signals converge, and drugs that pinch the funnel starve the tumour of the proteins it needs most.","route":"/pathways/mrna-translation-eif4f/","kind":"pathway","facets":{"kind":["Pathway"],"cancers":[],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[],"tags":[]},"sortKeys":{"year":0}},{"id":"mutagenesis-signatures","name":"Mutagenesis & mutational signatures","tldr":"Every cause of DNA damage leaves its own fingerprint in the genome: sunlight, tobacco, a faulty repair enzyme, a gut bacterium. Reading these fingerprints tells you what caused a cancer and which repair crews it is missing, which in turn predicts which drugs will work.","route":"/pathways/mutagenesis-signatures/","kind":"pathway","schematic":{"id":"wes-wgs","sections":["diagnostics","drug-discovery"]},"facets":{"kind":["Pathway"],"cancers":[],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[],"tags":[{"label":"mechanics-atlas","href":"/tagged/mechanics-atlas/","tip":"Every record tagged mechanics-atlas."}]},"sortKeys":{"year":0}},{"id":"myc","name":"MYC","tldr":"MYC is the most commonly amplified cancer gene, a master switch that turns on thousands of growth genes. It has no pocket for a conventional drug, so it remained 'undruggable' for 40 years; the first direct MYC drugs finally entered trials in the 2020s.","route":"/pathways/myc/","kind":"pathway","cancerIcon":"neuroblastoma","facets":{"kind":["Pathway"],"cancers":["Neuroblastoma","Diffuse large B-cell lymphoma","Pancreatic ductal adenocarcinoma"],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[{"label":"Neuroblastoma","href":"/cancers/neuroblastoma/","tip":"Neuroblastoma is a childhood nerve-cell cancer where anti-GD2 antibodies and, recently, GD2 CAR-T have improved survival in high-risk disease."},{"label":"Diffuse large B-cell lymphoma","href":"/cancers/dlbcl/","tip":"Diffuse large B-cell lymphoma (DLBCL) is an aggressive but curable lymphoma. CAR-T cures about 40% of relapsed patients, and off-the-shelf bispecifics are now approved."},{"label":"Pancreatic ductal adenocarcinoma","href":"/cancers/pancreatic/","tip":"Almost every pancreatic tumour carries a KRAS mutation, and for the first time drugs against it work: daraxonrasib nearly doubled survival in previously treated disease in 2026. Pancreatic cancer has been the hardest common cancer to treat once advanced; that is what is starting to change."}],"tags":[]},"sortKeys":{"year":0}},{"id":"myeloid-suppression-axis","name":"Myeloid suppression: TAMs, MDSCs & don't-eat-me signals","tldr":"Tumours recruit the body's clean-up cells (macrophages and immature myeloid cells) and re-train them as bodyguards. They switch off T cells, build vessels, and, when a therapeutic antibody flags a cancer cell for eating, are told 'don't eat me' by CD47 on its surface.","route":"/pathways/myeloid-suppression-axis/","kind":"pathway","schematic":{"id":"car-nk-macrophage","sections":["cell-therapy"]},"facets":{"kind":["Pathway"],"cancers":[],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[],"tags":[{"label":"mechanics-atlas","href":"/tagged/mechanics-atlas/","tip":"Every record tagged mechanics-atlas."}]},"sortKeys":{"year":0}},{"id":"nk-cell-recognition","name":"NK-cell recognition: missing self & stress ligands","tldr":"Natural killer cells patrol for cells that have lost their identity papers (MHC-I) or that display stress flags. Cancers that hide from T cells by dropping MHC-I become visible to NK cells, unless they also shed the stress flags, wrap themselves in a second inhibitory badge (HLA-E), or soak the neighbourhood in TGF-β.","route":"/pathways/nk-cell-recognition/","kind":"pathway","schematic":{"id":"car-nk-macrophage","sections":["cell-therapy"]},"facets":{"kind":["Pathway"],"cancers":[],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[],"tags":[{"label":"mechanics-atlas","href":"/tagged/mechanics-atlas/","tip":"Every record tagged mechanics-atlas."}]},"sortKeys":{"year":0}},{"id":"notch","name":"Notch signalling","tldr":"A cell-to-cell contact signal that decides cell fate. It drives T-cell leukaemia when mutated on, acts as a tumour suppressor in some squamous cancers when lost, and its ligand DLL3 became a drug target in small-cell lung cancer.","route":"/pathways/notch/","kind":"pathway","cancerIcon":"sclc","facets":{"kind":["Pathway"],"cancers":["Small-cell lung cancer","Acute lymphoblastic leukaemia","Chronic lymphocytic leukaemia","Head and neck squamous cell carcinoma"],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[{"label":"Small-cell lung cancer","href":"/cancers/sclc/","tip":"A fast-growing lung cancer that responds to chemotherapy then relapses quickly. After 30 years without progress, T-cell engagers and ADCs are finally moving the needle."},{"label":"Acute lymphoblastic leukaemia","href":"/cancers/all-leukemia/","tip":"Acute lymphoblastic leukaemia is the childhood cancer success story, and was the first disease treated with CAR-T and with a T-cell engager."},{"label":"Chronic lymphocytic leukaemia","href":"/cancers/cll/","tip":"A slow leukaemia that no longer needs chemotherapy: BTK inhibitors and venetoclax control it for years, often in fixed-duration courses."},{"label":"Head and neck squamous cell carcinoma","href":"/cancers/head-and-neck/","tip":"Cancers of the mouth and throat, increasingly caused by HPV. Immunotherapy is first line for advanced disease and now used before surgery."}],"tags":[]},"sortKeys":{"year":0}},{"id":"nutrient-competition-tme","name":"Nutrient competition & metabolic immunosuppression","tldr":"Tumours and immune cells eat from the same plate. Cancer cells hoard glucose and glutamine, dump lactate and acid, and burn tryptophan and arginine into by-products that paralyse T cells. The tumour wins the food fight, and the immune system loses before it has fired a shot.","route":"/pathways/nutrient-competition-tme/","kind":"pathway","schematic":{"id":"checkpoint-inhibitor","sections":["immunotherapy"]},"facets":{"kind":["Pathway"],"cancers":[],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[],"tags":[{"label":"mechanics-atlas","href":"/tagged/mechanics-atlas/","tip":"Every record tagged mechanics-atlas."}]},"sortKeys":{"year":0}},{"id":"oncogenic-viruses","name":"Oncogenic viruses","tldr":"About one cancer in eight worldwide is caused by a virus. HPV, hepatitis B and C, Epstein-Barr, HTLV-1, KSHV and Merkel cell polyomavirus each hijack the same brakes cancer normally has to mutate, which is why vaccines against HPV and HBV are among the most effective anti-cancer drugs ever made.","route":"/pathways/oncogenic-viruses/","kind":"pathway","cancerIcon":"cervical","facets":{"kind":["Pathway"],"cancers":["Cervical cancer","Head and neck squamous cell carcinoma","Nasopharyngeal carcinoma","Hepatocellular carcinoma","Merkel cell carcinoma","Kaposi sarcoma","Anal cancer","Hodgkin lymphoma"],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[{"label":"Cervical cancer","href":"/cancers/cervical/","tip":"A cancer that could be eliminated by HPV vaccination and screening. For those who develop it, immunotherapy and a tissue-factor ADC have improved survival."},{"label":"Head and neck squamous cell carcinoma","href":"/cancers/head-and-neck/","tip":"Cancers of the mouth and throat, increasingly caused by HPV. Immunotherapy is first line for advanced disease and now used before surgery."},{"label":"Nasopharyngeal carcinoma","href":"/cancers/nasopharyngeal/","tip":"A cancer at the back of the nose caused largely by the Epstein-Barr virus and common in southern China and Southeast Asia. Radiation cures most early cases; adding chemotherapy and, recently, PD-1 immunotherapy has improved outcomes in advanced disease, and a blood test for viral DNA can detect it early."},{"label":"Hepatocellular carcinoma","href":"/cancers/hcc/","tip":"Liver cancer almost always grows in a liver already damaged by hepatitis, alcohol or fatty liver disease. It is one of the most preventable cancers, and since 2020 immunotherapy combinations have roughly doubled how long people with advanced disease live."}],"tags":[{"label":"mechanics-atlas","href":"/tagged/mechanics-atlas/","tip":"Every record tagged mechanics-atlas."}]},"sortKeys":{"year":0}},{"id":"idea-senolytics-after-chemo","name":"One-two punch: clear senescent cells after chemotherapy","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.","route":"/ideas/idea-senolytics-after-chemo/","kind":"idea","cancerIcon":"tnbc","facets":{"kind":["Idea"],"cancers":["Triple-negative breast cancer","Ovarian cancer"],"year":[]},"cols":{"kind":{"facet":"kind","value":"Idea","tip":"Hypotheses and new directions, linked to the evidence."},"cancers":[{"label":"Triple-negative breast cancer","href":"/cancers/tnbc/","tip":"A breast cancer that lacks the three receptors (oestrogen, progesterone, HER2) that other breast cancers can be treated through. It was the hardest subtype for decades; since 2020 immunotherapy and ADCs have changed that."},{"label":"Ovarian cancer","href":"/cancers/ovarian/","tip":"Usually found late. PARP inhibitors transformed maintenance therapy, and ADCs against folate receptor and CDH6 are arriving for platinum-resistant disease."}],"tags":[{"label":"open-question","href":"/tagged/open-question/","tip":"Every record tagged open-question."}]},"sortKeys":{"year":0}},{"id":"organ-tropism-seed-soil","name":"Organ tropism: seed and soil","tldr":"Breast cancer goes to bone, lung, liver and brain; prostate cancer to bone; colon cancer to liver; uveal melanoma almost only to liver. Paget's 1889 idea still holds: where a cancer spreads depends on both the seed (the cell's programme) and the soil (the organ's welcome). Each soil has its own vicious cycle, and some are druggable.","route":"/pathways/organ-tropism-seed-soil/","kind":"pathway","cancerIcon":"prostate","facets":{"kind":["Pathway"],"cancers":["Prostate cancer","HR-positive / HER2-negative breast cancer","Colorectal cancer","Uveal melanoma","Ovarian cancer"],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[{"label":"Prostate cancer","href":"/cancers/prostate/","tip":"Prostate cancer is the home of theranostics: PSMA PET finds it, PSMA radioligands treat it. Hormonal therapy remains the foundation, with PARP and AKT inhibitors added by genotype."},{"label":"HR-positive / HER2-negative breast cancer","href":"/cancers/breast-hr-positive/","tip":"HR-positive breast cancer is the most common breast cancer, driven by oestrogen. It was treated for years with hormone-blocking pills, now joined by CDK4/6 inhibitors, PI3K-pathway drugs, degraders, and ADCs."},{"label":"Colorectal cancer","href":"/cancers/colorectal/","tip":"The cancer where screening works best and where immunotherapy can make some tumours disappear entirely, yet most metastatic disease still depends on chemotherapy."},{"label":"Uveal melanoma","href":"/cancers/uveal-melanoma/","tip":"A melanoma inside the eye that is biologically unrelated to skin melanoma: different mutations, no response to standard immunotherapy, and a tendency to spread to the liver years later. Tebentafusp is the first drug ever to extend survival in the metastatic disease."}],"tags":[{"label":"mechanics-atlas","href":"/tagged/mechanics-atlas/","tip":"Every record tagged mechanics-atlas."}]},"sortKeys":{"year":0}},{"id":"rtk-activation","name":"Receptor tyrosine kinase activation","tldr":"Growth-factor receptors are antennas on the cell surface that pair up when a signal lands and switch on the growth relays inside. Cancers mutate, multiply, or fuse these antennas so they broadcast 'grow' with no signal at all. Most targeted drugs, antibodies and ADCs start here.","route":"/pathways/rtk-activation/","kind":"pathway","cancerIcon":"nsclc","facets":{"kind":["Pathway"],"cancers":["Non-small-cell lung cancer","HER2-positive breast cancer","Gastric & gastro-oesophageal junction cancer","Gastrointestinal stromal tumour","Thyroid cancer","Biliary tract cancer"],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[{"label":"Non-small-cell lung cancer","href":"/cancers/nsclc/","tip":"Non-small-cell lung cancer is the proving ground for precision medicine: a dozen targetable mutations each with a matched pill, immunotherapy for the rest, and ADCs and bispecifics arriving now. Because most cases are still found late, low-dose CT screening is the other half of the story."},{"label":"HER2-positive breast cancer","href":"/cancers/breast-her2-positive/","tip":"HER2-positive breast cancer was once the most aggressive subtype and is now one of the most treatable, thanks to trastuzumab and, more recently, Enhertu."},{"label":"Gastric & gastro-oesophageal junction cancer","href":"/cancers/gastric/","tip":"A cancer with three new targets in five years: Claudin 18.2, FGFR2b, and HER2 with new ADCs, plus immunotherapy in first line."},{"label":"Gastrointestinal stromal tumour","href":"/cancers/gist/","tip":"GIST is a sarcoma of the gut wall driven almost always by a KIT or PDGFRA mutation. It was the proof that a pill can control a solid tumour: imatinib turned a median survival of about a year into one of eight years or more, and the mutation now dictates which drug to use."}],"tags":[{"label":"mechanics-atlas","href":"/tagged/mechanics-atlas/","tip":"Every record tagged mechanics-atlas."}]},"sortKeys":{"year":0}},{"id":"resistance-routes-map","name":"Resistance routes: how a blocked pathway comes back","tldr":"When a drug blocks a cancer's engine, the cancer has five ways back: change the part the drug binds, make more of it, take a side road, switch to a different engine altogether, or stop letting the drug in. Knowing which route a tumour took decides the next drug.","route":"/pathways/resistance-routes-map/","kind":"pathway","schematic":{"id":"liquid-biopsy","sections":["diagnostics"]},"facets":{"kind":["Pathway"],"cancers":[],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[],"tags":[{"label":"mechanics-atlas","href":"/tagged/mechanics-atlas/","tip":"Every record tagged mechanics-atlas."}]},"sortKeys":{"year":0}},{"id":"rna-splicing","name":"RNA splicing","tldr":"Genes are cut and pasted into messages before they are used. Blood cancers often carry mutations in the splicing machinery, and the errors create abnormal proteins that could serve as targets or immune flags.","route":"/pathways/rna-splicing/","kind":"pathway","cancerIcon":"aml","facets":{"kind":["Pathway"],"cancers":["Acute myeloid leukaemia","Chronic lymphocytic leukaemia","Melanoma","Prostate cancer"],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[{"label":"Acute myeloid leukaemia","href":"/cancers/aml/","tip":"Acute myeloid leukaemia is an aggressive blood cancer where, after 40 years of the same chemotherapy, a wave of targeted drugs (FLT3, IDH, BCL-2, menin) arrived."},{"label":"Chronic lymphocytic leukaemia","href":"/cancers/cll/","tip":"A slow leukaemia that no longer needs chemotherapy: BTK inhibitors and venetoclax control it for years, often in fixed-duration courses."},{"label":"Melanoma","href":"/cancers/melanoma/","tip":"The skin cancer that proved immunotherapy works: half of advanced patients now live 10 years. Also the first with an approved TIL therapy, an oncolytic virus, and a positive phase 3 personalised vaccine."},{"label":"Prostate cancer","href":"/cancers/prostate/","tip":"Prostate cancer is the home of theranostics: PSMA PET finds it, PSMA radioligands treat it. Hormonal therapy remains the foundation, with PARP and AKT inhibitors added by genotype."}],"tags":[]},"sortKeys":{"year":0}},{"id":"idea-splice-neoantigens","name":"Shared splice-derived neoantigens as off-the-shelf vaccine targets","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.","route":"/ideas/idea-splice-neoantigens/","kind":"idea","cancerIcon":"aml","facets":{"kind":["Idea"],"cancers":["Acute myeloid leukaemia","Chronic lymphocytic leukaemia","Melanoma"],"year":[]},"cols":{"kind":{"facet":"kind","value":"Idea","tip":"Hypotheses and new directions, linked to the evidence."},"cancers":[{"label":"Acute myeloid leukaemia","href":"/cancers/aml/","tip":"Acute myeloid leukaemia is an aggressive blood cancer where, after 40 years of the same chemotherapy, a wave of targeted drugs (FLT3, IDH, BCL-2, menin) arrived."},{"label":"Chronic lymphocytic leukaemia","href":"/cancers/cll/","tip":"A slow leukaemia that no longer needs chemotherapy: BTK inhibitors and venetoclax control it for years, often in fixed-duration courses."},{"label":"Melanoma","href":"/cancers/melanoma/","tip":"The skin cancer that proved immunotherapy works: half of advanced patients now live 10 years. Also the first with an approved TIL therapy, an oncolytic virus, and a positive phase 3 personalised vaccine."}],"tags":[{"label":"open-question","href":"/tagged/open-question/","tip":"Every record tagged open-question."}]},"sortKeys":{"year":0}},{"id":"swi-snf-chromatin","name":"SWI/SNF chromatin remodelling","tldr":"A machine that opens and closes DNA so genes can be read. One in five cancers has a broken part (ARID1A, SMARCA4, PBRM1), and losing one part often creates a dependence on its twin, which is the basis for new synthetic-lethal drugs.","route":"/pathways/swi-snf-chromatin/","kind":"pathway","cancerIcon":"rcc","facets":{"kind":["Pathway"],"cancers":["Renal cell carcinoma","Ovarian cancer","Non-small-cell lung cancer","Sarcomas"],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[{"label":"Renal cell carcinoma","href":"/cancers/rcc/","tip":"Kidney cancer is where anti-angiogenic drugs and immunotherapy came together, and where a Nobel-winning oxygen-sensing pathway yielded a drug, belzutifan."},{"label":"Ovarian cancer","href":"/cancers/ovarian/","tip":"Usually found late. PARP inhibitors transformed maintenance therapy, and ADCs against folate receptor and CDH6 are arriving for platinum-resistant disease."},{"label":"Non-small-cell lung cancer","href":"/cancers/nsclc/","tip":"Non-small-cell lung cancer is the proving ground for precision medicine: a dozen targetable mutations each with a matched pill, immunotherapy for the rest, and ADCs and bispecifics arriving now. Because most cases are still found late, low-dose CT screening is the other half of the story."},{"label":"Sarcomas","href":"/cancers/sarcoma/","tip":"Sarcomas are dozens of rare cancers of bone and connective tissue. GIST was the first solid tumour cured-in-practice by a targeted pill; synovial sarcoma got the first TCR-T therapy."}],"tags":[]},"sortKeys":{"year":0}},{"id":"synthetic-lethality-map","name":"Synthetic lethality: paired dependencies","tldr":"Two genes are synthetically lethal when losing either alone is fine but losing both kills the cell. Cancers that have already lost one (a tumour suppressor you cannot put back) become uniquely dependent on the other, which you can drug. BRCA and PARP was the first proof; a dozen more pairs are now in trials.","route":"/pathways/synthetic-lethality-map/","kind":"pathway","schematic":{"id":"synthetic-lethality-approaches","sections":["targeted-therapy","drug-discovery"]},"facets":{"kind":["Pathway"],"cancers":[],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[],"tags":[{"label":"mechanics-atlas","href":"/tagged/mechanics-atlas/","tip":"Every record tagged mechanics-atlas."}]},"sortKeys":{"year":0}},{"id":"t-cell-exhaustion","name":"T-cell exhaustion","tldr":"T cells that see their target for weeks on end without winning gradually shut down: they raise a set of brakes (PD-1, LAG-3, TIM-3, TIGIT), lose their ability to kill, and eventually lock this state into their DNA. Checkpoint drugs rescue the ones that are only partly exhausted; the terminally exhausted are beyond reach.","route":"/pathways/t-cell-exhaustion/","kind":"pathway","schematic":{"id":"checkpoint-inhibitor","sections":["immunotherapy"]},"facets":{"kind":["Pathway"],"cancers":[],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[],"tags":[{"label":"mechanics-atlas","href":"/tagged/mechanics-atlas/","tip":"Every record tagged mechanics-atlas."}]},"sortKeys":{"year":0}},{"id":"telomere-maintenance","name":"Telomere maintenance & replicative immortality","tldr":"Normal cells can divide only a limited number of times because the protective caps on their chromosomes, telomeres, wear down. About 90% of cancers switch the cap-rebuilding enzyme telomerase back on, often through TERT promoter mutations, and roughly 10% use an alternative lengthening route (ALT), so they divide indefinitely; imetelstat is the first approved telomerase inhibitor.","route":"/pathways/telomere-maintenance/","kind":"pathway","facets":{"kind":["Pathway"],"cancers":[],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[],"tags":[]},"sortKeys":{"year":0}},{"id":"tgf-beta","name":"TGF-β signalling","tldr":"A signal that stops normal cells from dividing but, once a cancer is established, switches sides: it builds scar-like stroma, walls out immune cells, and pushes cells into a migratory state.","route":"/pathways/tgf-beta/","kind":"pathway","facets":{"kind":["Pathway"],"cancers":[],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[],"tags":[]},"sortKeys":{"year":0}},{"id":"angiogenic-switch","name":"The angiogenic switch & tumour vessels","tldr":"A tumour cannot grow beyond a couple of millimetres without its own blood supply. The 'switch' flips when the signals calling for new vessels (VEGF, FGF, angiopoietin) outweigh the ones holding them back (thrombospondin). The vessels that result are leaky and chaotic, which starves the tumour of oxygen, blocks drugs, and gives cancer cells a way out.","route":"/pathways/angiogenic-switch/","kind":"pathway","cancerIcon":"rcc","facets":{"kind":["Pathway"],"cancers":["Renal cell carcinoma","Hepatocellular carcinoma","Colorectal cancer","Glioma & glioblastoma","Ovarian cancer"],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[{"label":"Renal cell carcinoma","href":"/cancers/rcc/","tip":"Kidney cancer is where anti-angiogenic drugs and immunotherapy came together, and where a Nobel-winning oxygen-sensing pathway yielded a drug, belzutifan."},{"label":"Hepatocellular carcinoma","href":"/cancers/hcc/","tip":"Liver cancer almost always grows in a liver already damaged by hepatitis, alcohol or fatty liver disease. It is one of the most preventable cancers, and since 2020 immunotherapy combinations have roughly doubled how long people with advanced disease live."},{"label":"Colorectal cancer","href":"/cancers/colorectal/","tip":"The cancer where screening works best and where immunotherapy can make some tumours disappear entirely, yet most metastatic disease still depends on chemotherapy."},{"label":"Glioma & glioblastoma","href":"/cancers/glioblastoma/","tip":"Gliomas are now diagnosed by molecular class, and three classes got their first targeted drugs in 2024-25 (vorasidenib for IDH-mutant glioma, tovorafenib for BRAF-altered paediatric glioma, dordaviprone for H3 K27M). Glioblastoma itself is the hardest to treat and has kept the same standard since 2005; CAR-T delivered into the brain and focused-ultrasound drug delivery are the live directions."}],"tags":[{"label":"mechanics-atlas","href":"/tagged/mechanics-atlas/","tip":"Every record tagged mechanics-atlas."}]},"sortKeys":{"year":0}},{"id":"blood-brain-barrier-metastasis","name":"The blood-brain barrier & brain metastasis","tldr":"The brain's blood vessels are sealed tight and fitted with pumps that eject most drugs. That protects the brain from poisons but also from chemotherapy and antibodies. Cancer cells that do squeeze through recruit the brain's own support cells, astrocytes, to feed and shield them.","route":"/pathways/blood-brain-barrier-metastasis/","kind":"pathway","cancerIcon":"nsclc","facets":{"kind":["Pathway"],"cancers":["Non-small-cell lung cancer","HER2-positive breast cancer","Melanoma","Small-cell lung cancer","Glioma & glioblastoma"],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[{"label":"Non-small-cell lung cancer","href":"/cancers/nsclc/","tip":"Non-small-cell lung cancer is the proving ground for precision medicine: a dozen targetable mutations each with a matched pill, immunotherapy for the rest, and ADCs and bispecifics arriving now. Because most cases are still found late, low-dose CT screening is the other half of the story."},{"label":"HER2-positive breast cancer","href":"/cancers/breast-her2-positive/","tip":"HER2-positive breast cancer was once the most aggressive subtype and is now one of the most treatable, thanks to trastuzumab and, more recently, Enhertu."},{"label":"Melanoma","href":"/cancers/melanoma/","tip":"The skin cancer that proved immunotherapy works: half of advanced patients now live 10 years. Also the first with an approved TIL therapy, an oncolytic virus, and a positive phase 3 personalised vaccine."},{"label":"Small-cell lung cancer","href":"/cancers/sclc/","tip":"A fast-growing lung cancer that responds to chemotherapy then relapses quickly. After 30 years without progress, T-cell engagers and ADCs are finally moving the needle."}],"tags":[{"label":"mechanics-atlas","href":"/tagged/mechanics-atlas/","tip":"Every record tagged mechanics-atlas."}]},"sortKeys":{"year":0}},{"id":"cancer-immunity-cycle","name":"The cancer-immunity cycle","tldr":"Seven steps the immune system must complete to kill a tumour: release of antigens, pick-up by dendritic cells, priming of T cells in lymph nodes, travel, entry into the tumour, recognition, and killing. Every immunotherapy pushes on one step; every escape blocks one.","route":"/pathways/cancer-immunity-cycle/","kind":"pathway","schematic":{"id":"checkpoint-inhibitor","sections":["immunotherapy"]},"facets":{"kind":["Pathway"],"cancers":[],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[],"tags":[{"label":"mechanics-atlas","href":"/tagged/mechanics-atlas/","tip":"Every record tagged mechanics-atlas."}]},"sortKeys":{"year":0}},{"id":"cell-cycle-engine-cdks","name":"The cell-cycle engine (cyclins & CDKs)","tldr":"Cell division runs on a clock made of cyclins and their kinases (CDKs), each pair firing in order: D-CDK4/6 to leave rest, E-CDK2 to start copying DNA, A-CDK2 to finish, B-CDK1 to divide. Cancers speed the clock; CDK inhibitors slow it.","route":"/pathways/cell-cycle-engine-cdks/","kind":"pathway","cancerIcon":"breast-hr-positive","facets":{"kind":["Pathway"],"cancers":["HR-positive / HER2-negative breast cancer","Sarcomas","Ovarian cancer","Small-cell lung cancer"],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[{"label":"HR-positive / HER2-negative breast cancer","href":"/cancers/breast-hr-positive/","tip":"HR-positive breast cancer is the most common breast cancer, driven by oestrogen. It was treated for years with hormone-blocking pills, now joined by CDK4/6 inhibitors, PI3K-pathway drugs, degraders, and ADCs."},{"label":"Sarcomas","href":"/cancers/sarcoma/","tip":"Sarcomas are dozens of rare cancers of bone and connective tissue. GIST was the first solid tumour cured-in-practice by a targeted pill; synovial sarcoma got the first TCR-T therapy."},{"label":"Ovarian cancer","href":"/cancers/ovarian/","tip":"Usually found late. PARP inhibitors transformed maintenance therapy, and ADCs against folate receptor and CDH6 are arriving for platinum-resistant disease."},{"label":"Small-cell lung cancer","href":"/cancers/sclc/","tip":"A fast-growing lung cancer that responds to chemotherapy then relapses quickly. After 30 years without progress, T-cell engagers and ADCs are finally moving the needle."}],"tags":[{"label":"mechanics-atlas","href":"/tagged/mechanics-atlas/","tip":"Every record tagged mechanics-atlas."}]},"sortKeys":{"year":0}},{"id":"metastatic-cascade","name":"The metastatic cascade","tldr":"How cancer spreads: cells leave the tumour, squeeze into blood or lymph vessels, survive the journey, exit into a new organ, often sleep there for years, and finally grow. Metastasis causes about 90% of cancer deaths.","route":"/pathways/metastatic-cascade/","kind":"pathway","schematic":{"id":"mrd-testing","sections":["diagnostics"]},"facets":{"kind":["Pathway"],"cancers":[],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[],"tags":[]},"sortKeys":{"year":0}},{"id":"p53-mdm2-axis","name":"The p53 network (guardian of the genome)","tldr":"p53 is the cell's emergency coordinator: DNA damage, oncogene stress or lack of oxygen switch it on, and it then pauses division, orders repairs, or triggers suicide or permanent retirement, while MDM2 keeps it off in healthy cells. About half of cancers mutate p53 outright, and sarcomas, gliomas, melanomas and retinoblastomas silence it instead by amplifying MDM2 or MDM4.","route":"/pathways/p53-mdm2-axis/","kind":"pathway","cancerIcon":"sarcoma","facets":{"kind":["Pathway"],"cancers":["Sarcomas","Chronic lymphocytic leukaemia","Myelodysplastic syndromes / neoplasms","Ovarian cancer"],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[{"label":"Sarcomas","href":"/cancers/sarcoma/","tip":"Sarcomas are dozens of rare cancers of bone and connective tissue. GIST was the first solid tumour cured-in-practice by a targeted pill; synovial sarcoma got the first TCR-T therapy."},{"label":"Chronic lymphocytic leukaemia","href":"/cancers/cll/","tip":"A slow leukaemia that no longer needs chemotherapy: BTK inhibitors and venetoclax control it for years, often in fixed-duration courses."},{"label":"Myelodysplastic syndromes / neoplasms","href":"/cancers/mds/","tip":"Bone-marrow disorders where blood cells are made badly and too few reach the blood; a third progress to acute leukaemia. Treatment ranges from transfusions and growth factors to hypomethylating drugs and, for the fit, transplant."},{"label":"Ovarian cancer","href":"/cancers/ovarian/","tip":"Usually found late. PARP inhibitors transformed maintenance therapy, and ADCs against folate receptor and CDH6 are arriving for platinum-resistant disease."}],"tags":[{"label":"mechanics-atlas","href":"/tagged/mechanics-atlas/","tip":"Every record tagged mechanics-atlas."}]},"sortKeys":{"year":0}},{"id":"pre-metastatic-niche","name":"The pre-metastatic niche","tldr":"Before a single cancer cell arrives, the primary tumour sends parcels ahead: tiny vesicles (exosomes) and hormones that recruit bone-marrow cells to a distant organ and remodel it into fertile soil. By the time the seed lands, the bed is already made.","route":"/pathways/pre-metastatic-niche/","kind":"pathway","schematic":{"id":"exosome-therapeutics","sections":["drug-discovery","targeted-therapy"]},"facets":{"kind":["Pathway"],"cancers":[],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[],"tags":[{"label":"mechanics-atlas","href":"/tagged/mechanics-atlas/","tip":"Every record tagged mechanics-atlas."}]},"sortKeys":{"year":0}},{"id":"theories-of-cancer","name":"Theories of cancer: how the ideas connect","tldr":"Scientists have given more than a dozen answers to what cancer is: mutated genes, runaway evolution, misbehaving stem cells, disordered tissue, ancient cell programmes, broken chromosomes, metabolism, epigenetic switches, unhealed wounds, a failed immune system, ageing tissue, force or electricity. This map shows each theory, who proposed it, what held up, and how the ideas connect.","route":"/pathways/theories-of-cancer/","kind":"pathway","facets":{"kind":["Pathway"],"cancers":[],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[],"tags":[{"label":"mechanics-atlas","href":"/tagged/mechanics-atlas/","tip":"Every record tagged mechanics-atlas."},{"label":"theory","href":"/tagged/theory/","tip":"Every record tagged theory."}]},"sortKeys":{"year":0}},{"id":"transcription-addiction","name":"Transcriptional machinery & addiction","tldr":"Cancer cells run a few genes (MYC, their lineage factors, their fusion oncogenes) at extreme volume from giant control regions called super-enhancers. The amplifiers, BRD4, CDK7, CDK9 and Mediator, are the same in every cell, but cancers are unusually dependent on them, and that dependence is druggable.","route":"/pathways/transcription-addiction/","kind":"pathway","cancerIcon":"ewing-sarcoma","facets":{"kind":["Pathway"],"cancers":["Ewing sarcoma","Acute myeloid leukaemia","Prostate cancer","HR-positive / HER2-negative breast cancer"],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[{"label":"Ewing sarcoma","href":"/cancers/ewing-sarcoma/","tip":"Ewing sarcoma is a bone and soft-tissue cancer of teenagers driven by a single fusion gene, EWSR1-FLI1. Intensive chemotherapy with surgery or radiation cures most localised cases; disease that has spread at diagnosis, and relapse, remain hard to treat, and no drug against the fusion protein itself has yet succeeded."},{"label":"Acute myeloid leukaemia","href":"/cancers/aml/","tip":"Acute myeloid leukaemia is an aggressive blood cancer where, after 40 years of the same chemotherapy, a wave of targeted drugs (FLT3, IDH, BCL-2, menin) arrived."},{"label":"Prostate cancer","href":"/cancers/prostate/","tip":"Prostate cancer is the home of theranostics: PSMA PET finds it, PSMA radioligands treat it. Hormonal therapy remains the foundation, with PARP and AKT inhibitors added by genotype."},{"label":"HR-positive / HER2-negative breast cancer","href":"/cancers/breast-hr-positive/","tip":"HR-positive breast cancer is the most common breast cancer, driven by oestrogen. It was treated for years with hormone-blocking pills, now joined by CDK4/6 inhibitors, PI3K-pathway drugs, degraders, and ADCs."}],"tags":[{"label":"mechanics-atlas","href":"/tagged/mechanics-atlas/","tip":"Every record tagged mechanics-atlas."}]},"sortKeys":{"year":0}},{"id":"idea-cachexia-gdf15-prevention","name":"Treat cachexia before it starts","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.","route":"/ideas/idea-cachexia-gdf15-prevention/","kind":"idea","cancerIcon":"pancreatic","facets":{"kind":["Idea"],"cancers":["Pancreatic ductal adenocarcinoma","Non-small-cell lung cancer","Gastric & gastro-oesophageal junction cancer"],"year":[]},"cols":{"kind":{"facet":"kind","value":"Idea","tip":"Hypotheses and new directions, linked to the evidence."},"cancers":[{"label":"Pancreatic ductal adenocarcinoma","href":"/cancers/pancreatic/","tip":"Almost every pancreatic tumour carries a KRAS mutation, and for the first time drugs against it work: daraxonrasib nearly doubled survival in previously treated disease in 2026. Pancreatic cancer has been the hardest common cancer to treat once advanced; that is what is starting to change."},{"label":"Non-small-cell lung cancer","href":"/cancers/nsclc/","tip":"Non-small-cell lung cancer is the proving ground for precision medicine: a dozen targetable mutations each with a matched pill, immunotherapy for the rest, and ADCs and bispecifics arriving now. Because most cases are still found late, low-dose CT screening is the other half of the story."},{"label":"Gastric & gastro-oesophageal junction cancer","href":"/cancers/gastric/","tip":"A cancer with three new targets in five years: Claudin 18.2, FGFR2b, and HER2 with new ADCs, plus immunotherapy in first line."}],"tags":[{"label":"open-question","href":"/tagged/open-question/","tip":"Every record tagged open-question."}]},"sortKeys":{"year":0}},{"id":"tumor-dormancy","name":"Tumour dormancy","tldr":"Cancer cells can hide in bone marrow, lung, or brain for years or decades, asleep and invisible to scans and chemotherapy, then wake up. Late relapse in breast and prostate cancer is dormancy ending.","route":"/pathways/tumor-dormancy/","kind":"pathway","cancerIcon":"breast-hr-positive","facets":{"kind":["Pathway"],"cancers":["HR-positive / HER2-negative breast cancer","Prostate cancer","Melanoma"],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[{"label":"HR-positive / HER2-negative breast cancer","href":"/cancers/breast-hr-positive/","tip":"HR-positive breast cancer is the most common breast cancer, driven by oestrogen. It was treated for years with hormone-blocking pills, now joined by CDK4/6 inhibitors, PI3K-pathway drugs, degraders, and ADCs."},{"label":"Prostate cancer","href":"/cancers/prostate/","tip":"Prostate cancer is the home of theranostics: PSMA PET finds it, PSMA radioligands treat it. Hormonal therapy remains the foundation, with PARP and AKT inhibitors added by genotype."},{"label":"Melanoma","href":"/cancers/melanoma/","tip":"The skin cancer that proved immunotherapy works: half of advanced patients now live 10 years. Also the first with an approved TIL therapy, an oncolytic virus, and a positive phase 3 personalised vaccine."}],"tags":[]},"sortKeys":{"year":0}},{"id":"tumor-microenvironment","name":"Tumour microenvironment (TME)","tldr":"A tumour is not just cancer cells. It is a neighbourhood of fibroblasts, immune cells, blood vessels, nerves, and scaffolding that the cancer recruits and corrupts, and that decides whether drugs and immune cells can get in.","route":"/pathways/tumor-microenvironment/","kind":"pathway","schematic":{"id":"single-cell-spatial","sections":["diagnostics","drug-discovery"]},"facets":{"kind":["Pathway"],"cancers":[],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[],"tags":[]},"sortKeys":{"year":0}},{"id":"ubiquitin-proteasome-system","name":"Ubiquitin-proteasome system & protein homeostasis","tldr":"Cells tag unwanted proteins with a small marker called ubiquitin and feed them into a shredder, the proteasome. Myeloma cells, which make antibody in bulk, die if the shredder jams; and the newest drugs hijack the tagging machinery to make a cancer destroy its own oncoproteins.","route":"/pathways/ubiquitin-proteasome-system/","kind":"pathway","cancerIcon":"multiple-myeloma","facets":{"kind":["Pathway"],"cancers":["Multiple myeloma","Mantle cell lymphoma","Prostate cancer","HR-positive / HER2-negative breast cancer"],"year":[]},"cols":{"kind":{"facet":"kind","value":"Pathway","tip":"The classic signalling circuits, drawn and explained."},"cancers":[{"label":"Multiple myeloma","href":"/cancers/multiple-myeloma/","tip":"Multiple myeloma is a plasma-cell cancer with more new drug classes than any other: proteasome inhibitors, IMiDs, CD38 antibodies, BCMA CAR-T, bispecifics, and an ADC."},{"label":"Mantle cell lymphoma","href":"/cancers/mantle-cell-lymphoma/","tip":"An uncommon B-cell lymphoma driven by cyclin D1 that used to behave badly in almost everyone. BTK inhibitors, CAR-T and now BCL2 drugs have changed it from chemotherapy-plus-transplant to targeted combinations."},{"label":"Prostate cancer","href":"/cancers/prostate/","tip":"Prostate cancer is the home of theranostics: PSMA PET finds it, PSMA radioligands treat it. Hormonal therapy remains the foundation, with PARP and AKT inhibitors added by genotype."},{"label":"HR-positive / HER2-negative breast cancer","href":"/cancers/breast-hr-positive/","tip":"HR-positive breast cancer is the most common breast cancer, driven by oestrogen. It was treated for years with hormone-blocking pills, now joined by CDK4/6 inhibitors, PI3K-pathway drugs, degraders, and ADCs."}],"tags":[{"label":"mechanics-atlas","href":"/tagged/mechanics-atlas/","tip":"Every record tagged mechanics-atlas."}]},"sortKeys":{"year":0}},{"id":"idea-immune-exclusion-drivers","name":"What actually holds T cells at the tumour border?","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.","route":"/ideas/idea-immune-exclusion-drivers/","kind":"idea","schematic":{"id":"single-cell-spatial","sections":["diagnostics","drug-discovery"]},"facets":{"kind":["Idea"],"cancers":[],"year":[]},"cols":{"kind":{"facet":"kind","value":"Idea","tip":"Hypotheses and new directions, linked to the evidence."},"cancers":[],"tags":[{"label":"open-question","href":"/tagged/open-question/","tip":"Every record tagged open-question."}]},"sortKeys":{"year":0}},{"id":"idea-dtc-colonisation-determinants","name":"What decides which disseminated cells ever colonise?","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.","route":"/ideas/idea-dtc-colonisation-determinants/","kind":"idea","cancerIcon":"breast-hr-positive","facets":{"kind":["Idea"],"cancers":["HR-positive / HER2-negative breast cancer","Triple-negative breast cancer","Prostate cancer"],"year":[]},"cols":{"kind":{"facet":"kind","value":"Idea","tip":"Hypotheses and new directions, linked to the evidence."},"cancers":[{"label":"HR-positive / HER2-negative breast cancer","href":"/cancers/breast-hr-positive/","tip":"HR-positive breast cancer is the most common breast cancer, driven by oestrogen. It was treated for years with hormone-blocking pills, now joined by CDK4/6 inhibitors, PI3K-pathway drugs, degraders, and ADCs."},{"label":"Triple-negative breast cancer","href":"/cancers/tnbc/","tip":"A breast cancer that lacks the three receptors (oestrogen, progesterone, HER2) that other breast cancers can be treated through. It was the hardest subtype for decades; since 2020 immunotherapy and ADCs have changed that."},{"label":"Prostate cancer","href":"/cancers/prostate/","tip":"Prostate cancer is the home of theranostics: PSMA PET finds it, PSMA radioligands treat it. Hormonal therapy remains the foundation, with PARP and AKT inhibitors added by genotype."}],"tags":[{"label":"open-question","href":"/tagged/open-question/","tip":"Every record tagged open-question."}]},"sortKeys":{"year":0}},{"id":"idea-neoantigen-immunogenicity-rules","name":"What makes a neoantigen actually immunogenic?","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.","route":"/ideas/idea-neoantigen-immunogenicity-rules/","kind":"idea","schematic":{"id":"neoantigen-mrna-vaccine","sections":["immunotherapy"]},"facets":{"kind":["Idea"],"cancers":[],"year":[]},"cols":{"kind":{"facet":"kind","value":"Idea","tip":"Hypotheses and new directions, linked to the evidence."},"cancers":[],"tags":[{"label":"open-question","href":"/tagged/open-question/","tip":"Every record tagged open-question."}]},"sortKeys":{"year":0}},{"id":"idea-chip-risk-modifiers","name":"Which patients' blood clones will become leukaemia after treatment?","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.","route":"/ideas/idea-chip-risk-modifiers/","kind":"idea","cancerIcon":"aml","facets":{"kind":["Idea"],"cancers":["Acute myeloid leukaemia","Ovarian cancer","Prostate cancer"],"year":[]},"cols":{"kind":{"facet":"kind","value":"Idea","tip":"Hypotheses and new directions, linked to the evidence."},"cancers":[{"label":"Acute myeloid leukaemia","href":"/cancers/aml/","tip":"Acute myeloid leukaemia is an aggressive blood cancer where, after 40 years of the same chemotherapy, a wave of targeted drugs (FLT3, IDH, BCL-2, menin) arrived."},{"label":"Ovarian cancer","href":"/cancers/ovarian/","tip":"Usually found late. PARP inhibitors transformed maintenance therapy, and ADCs against folate receptor and CDH6 are arriving for platinum-resistant disease."},{"label":"Prostate cancer","href":"/cancers/prostate/","tip":"Prostate cancer is the home of theranostics: PSMA PET finds it, PSMA radioligands treat it. Hormonal therapy remains the foundation, with PARP and AKT inhibitors added by genotype."}],"tags":[{"label":"open-question","href":"/tagged/open-question/","tip":"Every record tagged open-question."}]},"sortKeys":{"year":0}}]