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The Cancer Genome Atlas classified 333 prostate cancers taken out at surgery and found that three quarters fall into one of seven groups defined by a fusion or a mutation. A quarter had a change that a drug could in principle be aimed at, and one in five had a broken DNA repair gene.
The Cancer Genome Atlas Research Network profiled 333 primary prostate carcinomas across DNA, RNA, methylation and protein, and defined a taxonomy in which 74 percent of tumours belong to one of seven subtypes: the fusions ERG, ETV1, ETV4 and FLI1, and the mutations SPOP, FOXA1 and IDH1.
Androgen receptor activity varied widely and in a subtype-specific way, with SPOP and FOXA1 mutant tumours showing the highest androgen receptor-induced transcription. Twenty-five percent had a presumed actionable lesion in the PI3K or MAPK pathways, and DNA repair genes were inactivated in 19 percent, which is the finding that seeds the PARP inhibitor and platinum work in this disease. Roughly a quarter of primary prostate cancers still fall outside all seven subtypes, which is a candid statement of how much remains unclassified.
The reference classification of prostate cancer as it presents, and the source of the two numbers that drive most molecular treatment decisions in the disease: a quarter with a PI3K or MAPK lesion, which is the rationale for capivasertib in PTEN-deficient disease, and a fifth with DNA repair inactivation, which is the rationale for PARP inhibitors.
The genomic definition of advanced prostate cancer, and the evidence that made molecular testing standard in it. The 19.3 percent DNA repair figure is the direct ancestor of PROfound, TRITON3, PROpel and TALAPRO-2, and the 8 percent germline figure is why a tumour result in this disease has implications for a man's relatives.
The most common single molecular event in prostate cancer, present in roughly half of tumours in most series, and the reason prostate cancer is classified by fusion status. It is also a standing reminder that finding the driver and drugging it are different problems: no ETS-directed therapy has reached the clinic.
Shares TMPRSS2, FOXA1, Integrative genomic profiling of human prostate cancer, ERG and the tag prostate-evidence.
Shares TMPRSS2, ERG, SU2C-PCF: integrative clinical genomics of advanced prostate cancer, PTEN and the tag prostate-evidence.
Shares TMPRSS2, ERG, Cell, Localised prostate cancer, high and very high risk and the tag prostate-evidence.
Shares SU2C-PCF: integrative clinical genomics of advanced prostate cancer, Homologous recombination deficiency (HRD), Next-generation sequencing (NGS), 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 and the tag prostate-evidence.
Shares SU2C-PCF: integrative clinical genomics of advanced prostate cancer, Homologous recombination deficiency (HRD), Next-generation sequencing (NGS), 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 and the tag prostate-evidence.
Shares Homologous recombination deficiency (HRD), 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, Biomarkers are not validated or standardised, BRCA1 / BRCA2 (HRD) 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, Prostate cancer and the tag prostate-evidence.
Shares Next-generation sequencing (NGS), 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 and the tag prostate-evidence.