Loading
Tumours keep the body's repair cells in wound-healing mode forever. The scar they lay down squeezes vessels shut, walls out immune cells, and its very stiffness tells cancer cells to grow. Demolishing it made pancreatic cancer worse; retraining it is the new plan.
Pick a product above a diagram to see the nodes it hits and the escape routes below the block. Hover or tap any node or arrow for what it is; every node opens its target, glossary entry or the pathway page. Violet boxes are druggable targets.
Builders hired to repair a wall who never stop: they pour concrete around the tumour until the roads are blocked (vessels), the police cannot get in (T cells), and the very hardness of the concrete tells the tenants to multiply. Demolishing the builders' work made things worse; the newer plan is to retrain them.
A castle under siege from the inside: the cancer conscripts the town's builders (fibroblasts) to raise walls, bribes the guards (macrophages) to look away, and diverts the water supply (vessels) so that reinforcements (T cells, drugs) never arrive.
A building inspector (Hippo) who checks that the block is full and stops new floors. Cancers fire the inspector, and the architect (YAP/TAZ) keeps adding storeys.
In plain words, then the glossary entries the stage rests on. Chapter 8, The tumour ecosystem: A tumour is a corrupted organ: cancer cells plus the fibroblasts, matrix, vessels, nerves, microbes and immune cells they recruit, and the signals they send to the rest of the body.
Tumours keep the body's repair cells in wound-healing mode forever. The scar they lay down squeezes vessels shut, walls out immune cells, and its very stiffness tells cancer cells to grow. Demolishing it made pancreatic cancer worse; retraining it is the new plan.
Fibroblast activation, desmoplasia & matrix stiffness. 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.
Tumour microenvironment (TME). 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.
Hippo-YAP/TAZ. 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.
The proteins and genes at this stage, with their role and how many products act on each. Listed players come from the atlas; drawn players sit as nodes in the diagrams above.
The switch in the hedgehog developmental pathway that is stuck on in basal cell carcinoma and some medulloblastomas; three approved pills block it.
FAP (fibroblast activation protein) sits on the cancer-associated fibroblasts that scaffold more than 90% of epithelial cancers and is almost absent from normal adult tissue. FAPI PET tracers therefore light up tumours with high contrast, including pancreatic, gastric and low-grade cancers where FDG PET is weak, and FAP-targeted radioligands are in development.
PD-1 is a brake on T cells. Blocking it releases the immune system against the tumour and has cured some previously incurable cancers.
The signal tumours use to grow their own blood supply. Blocking it starves tumours and, surprisingly, helps immunotherapy work.
The first immune brake ever targeted for cancer; releasing it won a Nobel Prize and cures a fraction of melanomas.
The signalling enzyme that tells marrow cells to make red cells and platelets; a single mutation (V617F) leaves it switched on in most myeloproliferative neoplasms.
CD47 is the 'don't eat me' signal: it binds SIRP-alpha on macrophages to stop them engulfing the cell, and over 90% of AML blasts and large B-cell lymphoma cells display it. Blocking it should let macrophages eat tumour cells, but red cells carry CD47 too, so anaemia is built in, and the lead antibody magrolimab was dropped after failed trials.
Products grouped by the node they hit, most advanced first, with the cancers an approved product is linked to. Pick one above the diagram to see it light up.
Records tied to this stage that describe resistance, evasion or tolerance. Resistance: how tumours escape each drug class lists the routes class by class.
Biomarkers, tests and assays in the corpus that read this stage in a patient.
What is not known at this stage: the atlas's own questions, the bottlenecks it bears on, and the ideas in the corpus that try to answer them.
Pancreatic tumours are packed with a type of white blood cell that shuts down the immune attack. Blocking the signal that recruits them may open the tumour to immunotherapy.
Instead of finding a different target for each cancer, hit the scaffolding cells that almost all solid tumours share.
A rice-grain-sized implant releases microdoses of up to 20 drugs into separate spots of a tumour for one to three days, then is removed so pathologists can see which drug worked in that person's own tumour. First-in-human studies have been done in breast, sarcoma and brain tumours.
A cheap blood pressure drug may soften the dense scar tissue around pancreatic tumours so chemotherapy and immune cells can get in. Early trials look encouraging.
Focused ultrasound can break a tumour apart without heat or cuts, leaving debris the immune system can learn from. Doing that to one tumour may help treat the rest.
Interleukin-12 is an immune-stimulating cytokine that caused severe toxicity when injected into the bloodstream in the 1990s and was abandoned. An oncolytic herpes or adenovirus carrying the interleukin-12 gene under a drug-inducible promoter makes it only inside the tumour, keeping exposure local; trials include recurrent glioblastoma.
Tumours fill with immune cells that protect them. Earlier drugs tried to remove those cells and failed. Newer ones aim to switch them to the attacking side.
Ninety-five percent of advanced bowel cancers ignore immunotherapy, and the only real signal so far came in patients without active liver secondaries. Trials keep enrolling by treatment line rather than by immune biology, which guarantees the responders are diluted away.
Transferring gut bacteria from patients who responded to immunotherapy has helped some patients who had stopped responding. It is time for a proper large trial.
People who eat more fibre appear to respond better to immunotherapy, while some probiotic supplements may do the opposite. A proper trial would settle it.
25 more ideas are linked to this stage's pathways, targets and terms; see the rankings →
Papers in the corpus tied to this stage's pathways, targets and terms, newest first.
src/data/mechanics-atlas.ts). Players, medicines, escape routes, tests, ideas and papers are resolved from the knowledge graph at build time through the stage's pathways, targets and terms, so every item here has its own page and sources. Where a section is missing, the corpus has no record tied to the stage yet. Nothing here is medical advice; see about and methodology. Stage 8.1 of 56.