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Grip the scaffolding (integrins), dissolve a path (MMPs), haul forward (myosin), often along tracks that fibroblasts cut first. The protease blockers of the 1990s failed; the grip (FAK) is the modern target.
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.
A climber in a collapsing tunnel: grip the wall (integrins), chip away the rock ahead (MMPs), and haul forward (myosin). Some climbers squeeze through cracks without chipping (amoeboid). Often a guide (a fibroblast) has already carved the passage.
In plain words, then the glossary entries the stage rests on. Chapter 7, Invasion and metastasis: Metastasis causes about nine in ten cancer deaths, and no approved drug targets it directly.
Grip the scaffolding (integrins), dissolve a path (MMPs), haul forward (myosin), often along tracks that fibroblasts cut first. The protease blockers of the 1990s failed; the grip (FAK) is the modern target.
Invasion: proteases, adhesion & the invasive front. 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.
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.
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.
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.
You cannot manage what you do not measure quickly. Publishing stage at diagnosis by cancer and region every quarter, not years later, would show whether detection efforts are working.
Instead of finding a different target for each cancer, hit the scaffolding cells that almost all solid tumours share.
Guidelines send everyone whose chance-found gallbladder cancer has just reached the muscle layer back for liver and lymph node surgery, yet the largest international series found 95 in 100 alive without the disease at five years whether or not they had it. A prospective study could spare thousands of operations, or confirm they are needed.
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.
TGF-beta is a signal that keeps immune cells out of tumours, but blocking it throughout the body caused bleeding and heart toxicity and sank bintrafusp alfa. Tethering the blocker to tumour stroma with a FAP anchor, a collagen-binding domain or a protease-activated mask could give the benefit without the harm.
Cancer cells can survive a drug because surrounding normal cells feed them growth signals. Blocking those signals could make existing drugs work better and longer.
Immunotherapy works in tumours that immune cells can enter and ignores those that shut them out. Systematically test ways to open up the shut-out tumours, measured with spatial maps.
Pancreatic tumours are mostly scar tissue. The first attempt to dissolve it, an enzyme given with chemotherapy to nearly 500 patients, shrank more tumours but did not lengthen life, and mouse work showed that stripping out the scar-forming cells made cancers worse. The proposal is to test drugs that change what the stroma does rather than remove it, in trials measured on survival.
When a blood test says 'cancer signal, origin unclear', a FAPI PET scan may find it where FDG cannot.
The support cells that build a tumour's scaffolding come in several types: some protect the tumour, others restrain it. Treating all of them the same way explains past failures.
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 7.2 of 56.