Tissue architecture and the basement membrane
Organs are built like walled towns. Lining cells sit on a dense protein sheet, the basement membrane, and hold hands through junctions. A growth that stays above the sheet is 'in situ' and almost always curable; the disease becomes cancer proper when it cuts through.
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 shop floor with a locked glass floor beneath it. Staff (epithelial cells) can be unruly upstairs and it is still contained; the emergency begins when someone cuts through the glass into the building services below, where the plumbing (blood and lymph vessels) runs.
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.
What happens
In plain words, then the glossary entries the stage rests on. Chapter 1, The body's defences: Cancer is not the default.
Organs are built like walled towns. Lining cells sit on a dense protein sheet, the basement membrane, and hold hands through junctions. A growth that stays above the sheet is 'in situ' and almost always curable; the disease becomes cancer proper when it cuts through.
Basement membrane & tissue barriers. 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.
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 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.
No target record is listed at this stage or drawn in its diagrams; the pathways above carry the mechanism.
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.
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.
- Which in situ lesions will never progress, so that screening stops over-treating?
- Can the breach itself be imaged or detected in blood before it happens?
- being tested at scaleNon-endoscopic screening for Barrett's oesophagus and early adenocarcinoma
A swallowed sponge on a string can sample the oesophagus in a GP's office. Screen people with chronic reflux to catch adenocarcinoma at a curable stage.
- 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 clinicalIntercept cancer at the field stage
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.
- early clinicalregulatorRequire stage-shift or interval-cancer endpoints for AI in cancer screening
AI for screening should be judged on whether it finds dangerous cancers earlier and misses fewer, not just on whether it agrees with radiologists on old images.
- preclinical evidenceresearchMolecular indolence classifiers bundled with every screening programme
Screening finds cancers that would never have caused harm alongside dangerous ones. Pair every screening test with a test that says which is which, so people with harmless findings can safely watch and wait.
- speculativepolicyA whole-population cancer interception programme: risk-stratify every adult, detect and intercept early
Instead of separate screening programmes for a few cancers, assess every adult's overall cancer risk and offer blood tests, imaging and preventive treatment tuned to that risk, all inside one system that learns.
- speculativeregulatorLet MCED trials read out on late-stage incidence, with mortality follow-up mandated
Multi-cancer early detection blood tests take a decade to prove they save lives. Regulators could accept a fall in late-stage cancers as the first answer, validated against pooled data from completed screening trials, provided approval is conditional on continued mortality follow-up.
- speculativeresearchOpen-source models that translate stage shift into lives saved, for every cancer
Whether finding cancer earlier saves lives depends on the cancer. Public models, one per cancer, would let trials and payers predict the mortality benefit from a stage shift honestly.
- speculativepayerPay insurers and health systems for cancers prevented and caught early
Health systems earn from treating cancer, not preventing it. Paying them for lower cancer incidence and earlier stage in their population would flip the incentive.
- speculativeresearchRegistry-based randomised MCED trial: a million people, no study visits
Randomise people through the national health system, post the blood kit, and read cancer deaths off the registry. That is ten times cheaper per participant than a classic trial.
Key evidence
Papers in the corpus tied to this stage's pathways, targets and terms, newest first.
- 2026rctPerformance of a multi-cancer early detection test in the randomized controlled NHS-Galleri trialNature Medicine
- 2023reviewInsights into recent findings and clinical application of YAP and TAZ in cancerNature Reviews Cancer
- 2023observationalPATHFINDER: the first prospective test of a multi-cancer blood test in people without symptomsThe Lancet
- 2022methodsNHS-Galleri: design of the largest randomised trial of a multi-cancer blood testCancers
- 2020observationalDETECT-A: a blood test plus PET-CT found treatable cancers in 10,000 women with no symptomsScience
- 2020rctNELSON: volume-based CT screening reduces lung cancer deaths with fewer false alarmsNew England Journal of Medicinechanged practice
- 2014reviewTraversing the basement membrane in vivo: a diversity of strategiesThe Journal of cell biology
- 2011rctNLST: yearly low-dose CT scans cut lung cancer deaths in heavy smokersNew England Journal of Medicinechanged practice
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 1.1 of 56.