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By sequencing many separate deposits from ten men who died of prostate cancer, this study reconstructed how the cancer travelled. Metastases seeded other metastases, and often did it in groups of cells rather than one at a time.
Gunes Gundem, David Wedge, Peter Campbell, Scott Bova and the International Cancer Genome Consortium Prostate Group used whole-genome sequencing of multiple metastases from ten men with androgen-deprived metastatic prostate cancer and reconstructed the subclonal architecture across sites.
The standard model of metastasis is that each deposit descends from one cell that left the primary tumour. This work found that metastasis-to-metastasis spread is common, either by a daughter metastasis being seeded from a parent one, or, in five of the ten men, by multiple tumour clones moving between metastatic sites together. It also found a pattern in what is mutated where: tumour suppressor lesions occur as single events, whereas androgen receptor pathway mutations arise convergently and repeatedly in different metastases, which is evolution being watched under the same selective pressure in parallel.
Metastatic prostate cancer is a communicating population, not a set of independent colonies, which is an argument for treating the whole body rather than chasing individual deposits, and an argument that resistance to androgen receptor drugs will emerge in several places at once because it emerges convergently.
One technology page, one pathway page and one term page on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.
A different picture of how a cancer genome is built, and one that explains why prostate cancer has few point mutations and a great deal of structural damage. It is also why whole-genome rather than exome sequencing is the right assay for this disease.
Shares Punctuated evolution of prostate cancer genomes, Chromoplexy, Nature, Tumour heterogeneity and clonal evolution and the tag prostate-evidence.
Shares Tumour heterogeneity and clonal evolution, Prostate cancer roadmap: from Huggins and the discovery that a cancer can depend on a hormone, through the PSA epidemic and what it cost, the androgen receptor drugs, the DNA repair subset and PSMA, to a 2032 registry watch, Androgen receptor, Acquired resistance to every therapy and the tag prostate-evidence.
Shares Integrating evolutionary dynamics into treatment of metastatic castrate-resistant prostate cancer, Prostate cancer roadmap: from Huggins and the discovery that a cancer can depend on a hormone, through the PSA epidemic and what it cost, the androgen receptor drugs, the DNA repair subset and PSMA, to a 2032 registry watch, Androgen receptor, Acquired resistance to every therapy and the tag prostate-evidence.
Shares Tumour heterogeneity and clonal evolution, Prostate cancer roadmap: from Huggins and the discovery that a cancer can depend on a hormone, through the PSA epidemic and what it cost, the androgen receptor drugs, the DNA repair subset and PSMA, to a 2032 registry watch, Androgen receptor, Acquired resistance to every therapy and the tag prostate-evidence.
Shares Prostate cancer roadmap: from Huggins and the discovery that a cancer can depend on a hormone, through the PSA epidemic and what it cost, the androgen receptor drugs, the DNA repair subset and PSMA, to a 2032 registry watch, Androgen receptor, Acquired resistance to every therapy, Metastatic castration-resistant prostate cancer and the tag prostate-evidence.
Shares Prostate cancer roadmap: from Huggins and the discovery that a cancer can depend on a hormone, through the PSA epidemic and what it cost, the androgen receptor drugs, the DNA repair subset and PSMA, to a 2032 registry watch, Androgen receptor, Acquired resistance to every therapy, Metastatic castration-resistant prostate cancer and the tag prostate-evidence.
Shares Tumour heterogeneity and clonal evolution, Prostate cancer roadmap: from Huggins and the discovery that a cancer can depend on a hormone, through the PSA epidemic and what it cost, the androgen receptor drugs, the DNA repair subset and PSMA, to a 2032 registry watch, Androgen receptor, Acquired resistance to every therapy and the tag prostate-evidence.
Shares Prostate cancer roadmap: from Huggins and the discovery that a cancer can depend on a hormone, through the PSA epidemic and what it cost, the androgen receptor drugs, the DNA repair subset and PSMA, to a 2032 registry watch, Androgen receptor, Acquired resistance to every therapy, Metastatic castration-resistant prostate cancer and the tag prostate-evidence.