# The metastatic cascade

Source: https://onco.cc/pathways/metastatic-cascade/  
OnCo record `metastatic-cascade` (Pathway). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

How cancer spreads: cells leave the tumour, squeeze into blood or lymph vessels, survive the journey, exit into a new organ, often sleep there for years, and finally grow. Metastasis causes about 90% of cancer deaths.

## Summary

Invasion (EMT, matrix proteases), intravasation, survival in circulation as CTCs or clusters (platelet cloaking, anoikis resistance), arrest and extravasation, then colonisation, which is the rate-limiting step: most disseminated tumour cells (DTCs) die or stay dormant. Organ tropism follows Paget's seed-and-soil: pre-metastatic niches are prepared by tumour-derived exosomes and myeloid cells. Clinically, ctDNA and MRD assays detect the cascade before imaging; adjuvant therapy targets it blind; no drug specifically blocks colonisation yet.

## Fields

- Kind: Pathway
- Last checked: 2026-09-08
- Tags: mechanism
- Analogy: A seed leaving a plant: it must detach, ride the wind, land somewhere with the right soil, survive the winter, and only then sprout. Almost every seed fails; the few that grow are the metastases.
- Interventions: Adjuvant systemic therapy and ctDNA-guided escalation aim at DTCs before colonisation; Anti-EMT and anti-MMP drugs failed historically; TGF-β blockade is being retried in combinations; Dormancy-maintaining strategies (see tumour dormancy) are the newest idea; Metastasis-directed SBRT for oligometastatic disease

## Notes

- Leading programmes: Massagué lab (MSK) on metastasis-initiating cells and dormancy; Swanton/TRACERx (Crick) on evolution and dissemination timing; Egeblad (CSHL) on neutrophils and dormancy awakening; DKFZ Metastasis Research.
- Massagué & Ganesh, Cancer Cell 2023 review: https://doi.org/10.1016/j.ccell.2023.02.020

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Metastasis
- Massagué & Obenauf, Metastatic colonization by circulating tumour cells (Nature 2016): https://doi.org/10.1038/nature17038
- Gerstberger, Jiang & Ganesh, Metastasis (Cell 2023): https://doi.org/10.1016/j.cell.2023.03.003

## Connected records

- technologies: [Liquid biopsy (ctDNA)](https://onco.cc/technologies/liquid-biopsy/), [MRD / molecular residual disease testing](https://onco.cc/technologies/mrd-testing/), [SBRT / SABR (stereotactic radiotherapy)](https://onco.cc/technologies/sbrt/), [Single-cell & spatial profiling](https://onco.cc/technologies/single-cell-spatial/)
- institutions: [Cold Spring Harbor Laboratory](https://onco.cc/institutions/cold-spring-harbor/), [German Cancer Research Center (DKFZ)](https://onco.cc/institutions/dkfz/), [Memorial Sloan Kettering Cancer Center](https://onco.cc/institutions/mskcc/), [The Francis Crick Institute](https://onco.cc/institutions/francis-crick/)
- pathways: [Cancer neuroscience (nerve-tumour signalling)](https://onco.cc/pathways/cancer-neuroscience/), [Clonal evolution & minimal residual disease](https://onco.cc/pathways/clonal-evolution/), [Epithelial-mesenchymal transition & drug efflux](https://onco.cc/pathways/emt/), [Intravasation & circulating tumour cells](https://onco.cc/pathways/intravasation-ctc-survival/), [Invasion: proteases, adhesion & the invasive front](https://onco.cc/pathways/invasion-ecm-degradation/), [Organ tropism: seed and soil](https://onco.cc/pathways/organ-tropism-seed-soil/), [TGF-β signalling](https://onco.cc/pathways/tgf-beta/), [The blood-brain barrier & brain metastasis](https://onco.cc/pathways/blood-brain-barrier-metastasis/), [The pre-metastatic niche](https://onco.cc/pathways/pre-metastatic-niche/), [Tumour dormancy](https://onco.cc/pathways/tumor-dormancy/), [Tumour microenvironment (TME)](https://onco.cc/pathways/tumor-microenvironment/)
- terms: [Circulating tumour DNA (ctDNA)](https://onco.cc/terms/ctdna/), [Disseminated tumour cells (DTCs)](https://onco.cc/terms/disseminated-tumor-cells/), [Hallmark: activating invasion and metastasis](https://onco.cc/terms/activating-invasion-metastasis/), [Metastasis](https://onco.cc/terms/metastasis/), [Minimal / molecular residual disease (MRD)](https://onco.cc/terms/mrd/), [Oligometastatic disease](https://onco.cc/terms/oligometastatic/), [Primary tumour](https://onco.cc/terms/primary-tumour/), [Seed and soil hypothesis of metastasis (Paget)](https://onco.cc/terms/seed-and-soil-hypothesis/)
- key papers: [Distant metastasis occurs late during the genetic evolution of pancreatic cancer](https://onco.cc/key-papers/paper-yachida-metastasis-late-genetic-evolution-pancreatic-nature-2010/), [DPC4 gene status of the primary carcinoma correlates with patterns of failure in patients with pancreatic cancer](https://onco.cc/key-papers/paper-iacobuzio-donahue-dpc4-failure-pattern-autopsy-jco-2009/), [Kalluri and Weinberg 2009: the basics of epithelial-mesenchymal transition](https://onco.cc/key-papers/paper-kalluri-weinberg-emt-basics-jci-2009/), [Metastasis](https://onco.cc/key-papers/paper-gerstberger-cell/), [Metastatic colonization by circulating tumour cells](https://onco.cc/key-papers/paper-massague-nature/), [Quail and Joyce 2013: microenvironmental regulation of tumour progression and metastasis](https://onco.cc/key-papers/paper-quail-joyce-microenvironment-metastasis-natmed-2013/), [TGF-beta drives immune evasion in genetically reconstituted colon cancer metastasis](https://onco.cc/key-papers/paper-tauriello-tgfbeta-immune-evasion-colorectal-nature-2018/), [Thiery 2002: epithelial-mesenchymal transitions in tumour progression](https://onco.cc/key-papers/paper-thiery-emt-tumour-progression-nrc-2002/)
- ideas: [Keep them asleep: dormancy maintenance as adjuvant therapy](https://onco.cc/ideas/idea-dormancy-maintenance-therapy/), [What decides which disseminated cells ever colonise?](https://onco.cc/ideas/idea-dtc-colonisation-determinants/)

---
JSON: https://onco.cc/api/v1/entities/metastatic-cascade.json