Organ tropism
Breast cancer goes to bone, lung, liver and brain; prostate to bone; colon to liver. Seed and soil: the cell's programme and the organ's welcome. Bone's vicious cycle of tumour and osteoclast is the one we can already drug.
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.
Dandelion seeds fall everywhere, but only take root where the soil suits them. Bone is a greenhouse for breast and prostate seeds because the seeds can trick the gardeners (osteoclasts) into digging up food for them.
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.
Breast cancer goes to bone, lung, liver and brain; prostate to bone; colon to liver. Seed and soil: the cell's programme and the organ's welcome. Bone's vicious cycle of tumour and osteoclast is the one we can already drug.
Organ tropism: seed and soil. 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.
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.
A protein on prostate cancer cells that lets doctors both see the cancer on a PET scan and hit it with a radioactive drug.
A chemokine receptor that anchors blood cells in the marrow and helps cancer cells home to it; mutated in a third of Waldenström patients and targeted by plerixafor for stem-cell mobilisation.
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.
- Lutetium-177 vipivotide tetraxetanApprovedProstate cancerMetastatic castration-resistant prostate cancerMetastatic hormone-sensitive prostate cancer
- Flotufolastat F-18ApprovedProstate cancer
- Gallium-68 gozetotide (PSMA-11)ApprovedProstate cancer
- Illuccix (kit for Ga-68 gozetotide)ApprovedProstate cancer
- Locametz (kit for Ga-68 gozetotide)ApprovedProstate cancer
- Piflufolastat F-18 / Pylarify TruVuApprovedProstate cancer
- 177Lu-PSMA-I&TPhase 3
- AAA817Phase 3
- +7 more at PSMA →
How tumours escape
Records tied to this stage that describe resistance, evasion or tolerance. The resistance atlas lists the routes class by class.
- early clinicalresearchA test to tell true oligometastatic disease from hidden widespread spread
Some people have only a few sites of spread and can be treated at each one; others have further deposits not yet visible, and counting lesions cannot tell them apart. A signature built from tumour DNA levels, microRNA classifiers and clonal diversity across lesions would define the biology and spare futile ablation.
- early clinicalclinicBiopsy the one lesion that is growing while the others shrink
When a scan shows most tumours shrinking but one growing, that odd lesion holds the escape mechanism. Sampling it, and treating it locally, should be routine.
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 treating oligometastases with SBRT change survival across cancers, or only in selected ones?
- Can tropism be predicted from the primary tumour to target surveillance?
- being tested at scalePSMA-PET-guided metastasis-directed therapy as a curative strategy in oligorecurrent prostate cancer
When PSMA PET finds only a few spots after surgery, zap each spot with focused radiation and delay or avoid lifelong hormone therapy.
- early clinicalresearchA neutral platform trial for radiotherapy plus immunotherapy combinations
Radiotherapy may make immunotherapy work better, but the trials to test this are scattered and often small. One shared platform, run by radiotherapy groups with drugs supplied by several companies, would settle it faster.
- early clinicalPeritoneal-directed therapy for gastric cancer
Stomach cancer usually comes back on the abdominal lining, where drugs barely reach. Deliver treatment directly into the abdomen.
- early clinicalclinicTreat the body cavity, not the bloodstream, for surface spread
Intracavitary immunotherapy targets cancer that coats the lining of the abdomen or chest, which drugs given by drip barely reach. Delivering it straight into the cavity gives far higher local doses.
- early clinicalclinicWhen the blood test is positive, hunt for the lesion with sensitive imaging
A positive blood test tells you cancer is back but not where. Combining whole-body MRI with modern PET tracers may find a single spot that can be zapped.
- preclinical evidenceresearchReprogramme the liver's own immune cells to refuse metastases
The liver is where bowel cancer most often spreads. Drugs delivered straight into the liver's blood supply could retrain its resident immune cells to reject arriving cancer cells.
- speculativeregulatorA regulatory endpoint for drugs that block spread, not tumours
Today a cancer drug is approved for shrinking tumours. A drug that stopped cancer spreading would fail that test, so almost nobody develops one. A new endpoint would fix that.
- speculativepolicyA ring-fenced metastasis programme with metastasis-specific endpoints
Metastasis causes about nine in ten cancer deaths but gets a small slice of research money. This would ring-fence a tenth of national cancer research budgets for the biology and trials of spread itself.
- speculativeengineeringBuild laboratory models of the organs cancer spreads to
Cancer usually kills by spreading to bone, liver, lung or brain. Almost all laboratory models grow tumours under the skin instead, where the surroundings are nothing like those organs.
Key evidence
Papers in the corpus tied to this stage's pathways, targets and terms, newest first.
- 2021rctVISION: lutetium-177 PSMA-617 radioligand therapy extends survival in advanced prostate cancerNew England Journal of Medicinechanged practice
- 2020reviewDefining oligometastatic disease from a radiation oncology perspective: An ESTRO-ASTRO consensus documentRadiotherapy and Oncology
- 2015reviewSurviving at a Distance: Organ-Specific MetastasisTrends in cancer
- 2014observationalSomatic mutations in MYD88 and CXCR4 are determinants of clinical presentation and overall survival in Waldenstrom macroglobulinemiaBlood
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 7.6 of 56.