The metastatic cascade
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.
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.
In one picture
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.
Diagram
top- 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
top- 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
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not linked directly; found by shared links- PathwayHippo–YAP/TAZ
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