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When hormone treatment stops working, the cancer often has not stopped caring about the hormone. In a third of tumours that came back on treatment, the cell had simply made extra copies of the androgen receptor gene so it could live on the tiny amount of hormone left.
Tapio Visakorpi and colleagues in Tampere used comparative genomic hybridisation on tumours taken before androgen deprivation and again when they recurred on it, in the same patients. Amplification of the Xq11-q13 region, which carries the androgen receptor gene, appeared in the recurrent tumours and in none of the pre-treatment samples from the same men.
The finding reframed what castration resistance is. The old name, hormone-refractory prostate cancer, implied that the tumour had stopped using the androgen pathway. This paper said the opposite: the tumour had adapted to keep using it in a low-androgen environment. That is why abiraterone, enzalutamide, apalutamide and darolutamide work at all, and why they were built.
The first evidence that resistance to hormone therapy in prostate cancer is an adaptation of the target rather than an escape from it, which is why the field kept building better androgen receptor drugs instead of abandoning the pathway.
The design specification for the second-generation antiandrogens. A drug for castration-resistant prostate cancer has to stay an antagonist when the receptor is abundant, which is what enzalutamide, apalutamide and darolutamide were engineered to do and what bicalutamide fails to do.
The origin of hormone therapy for cancer, and the reason prostate cancer is treated by taking something away rather than adding a cytotoxic drug. More than eighty years later, every man who starts androgen deprivation is having this experiment repeated on him, and the disease is still defined by whether it has stopped responding to it.
Shares Molecular determinants of resistance to antiandrogen therapy, Take high-dose testosterone to phase 3, with progression-free survival through the second line as the primary endpoint, Castration-resistant prostate cancer (CRPC), 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 Molecular determinants of resistance to antiandrogen therapy, Take high-dose testosterone to phase 3, with progression-free survival through the second line as the primary endpoint, Castration-resistant prostate cancer (CRPC), 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 Molecular determinants of resistance to antiandrogen therapy, Castration-resistant prostate cancer (CRPC), 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.
Shares Molecular determinants of resistance to antiandrogen therapy, Castration-resistant prostate cancer (CRPC), 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.
Shares Take high-dose testosterone to phase 3, with progression-free survival through the second line as the primary endpoint, Castration-resistant prostate cancer (CRPC), 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.
Shares Castration-resistant prostate cancer (CRPC), 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 Castration-resistant prostate cancer (CRPC), 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, Acquired resistance to every therapy, Metastatic castration-resistant prostate cancer and the tag prostate-evidence.