Invasion
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.
Diagram
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.
What happens
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 molecular players
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.
Where medicines act
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.
- EB-MF-CAR-NK-01Phase 2
- FAP-2286 (177Lu / 68Ga)Phase 2
How tumours escape
Records tied to this stage that describe resistance, evasion or tolerance. The resistance atlas lists the routes class by class.
Measured by
Biomarkers, tests and assays in the corpus that read this stage in a patient.
Open questions
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.
- Does FAK inhibition reduce metastasis, or only soften stroma for other drugs?
- Can perineural invasion be blocked pharmacologically?
- early clinicaldataA live national dashboard of stage at diagnosis as the scorecard for early detection
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.
- early clinicalFAP theranostics as a pan-cancer stromal strategy
Instead of finding a different target for each cancer, hit the scaffolding cells that almost all solid tumours share.
- early clinicalWhat actually holds T cells at the tumour border?
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.
- preclinical evidenceindustryAnchor a TGF-beta trap in the tumour stroma so it cannot act everywhere
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.
- preclinical evidenceresearchBlock the survival signals the tumour's neighbours provide
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.
- preclinical evidenceresearchMake every cold tumour hot: a coordinated programme to reprogramme immune-excluded tumours
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.
- speculativeFAPI PET as the workup for MCED positives
When a blood test says 'cancer signal, origin unclear', a FAPI PET scan may find it where FDG cannot.
- speculativeresearchMatch therapy to the type of scar-forming cell in the tumour
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.
Key evidence
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.