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Comparing prostate tumours before and after hormone treatment in the same men showed that a third of the ones that came back had made extra copies of the very gene the treatment was aimed at.
Comparative genomic hybridisation was used on tumours recurring during androgen deprivation therapy and on specimens taken from the same patients before therapy. Amplification of the Xq11-q13 region, which carries the androgen receptor gene, was common in the recurrent tumours: high-level amplification was present in 7 of 23 recurrent tumours, 30%, and in none of the pre-therapy specimens from the same patients. The authors proposed that amplification emerges during androgen deprivation by allowing tumour cells to grow in low androgen concentrations, the same logic by which amplified genes confer drug resistance in vitro.
It was the first demonstration in a human solid tumour that endocrine treatment fails by amplifying the drug's own target, and it is the origin of the idea that castration-resistant prostate cancer is still androgen receptor-driven, which is what made abiraterone and enzalutamide worth developing.
Shares Androgen deprivation therapy (ADT), Androgen receptor signalling, Castration-resistant prostate cancer (CRPC), Drug resistance (primary and acquired).
Shares AR amplification (gene and upstream enhancer), Gene amplification and copy-number change, Androgen receptor signalling, Castration-resistant prostate cancer (CRPC).
Shares Nature Genetics, Androgen deprivation therapy (ADT), Castration-resistant prostate cancer (CRPC), Androgen receptor.
Shares Androgen receptor signalling, Castration-resistant prostate cancer (CRPC), Drug resistance (primary and acquired), Androgen receptor.
Shares Androgen receptor signalling, Castration-resistant prostate cancer (CRPC), Drug resistance (primary and acquired), Androgen receptor.
Shares Androgen receptor signalling, Castration-resistant prostate cancer (CRPC), Drug resistance (primary and acquired), Androgen receptor.
Shares AR amplification (gene and upstream enhancer), Androgen receptor signalling, Castration-resistant prostate cancer (CRPC), Drug resistance (primary and acquired).
Shares AR amplification (gene and upstream enhancer), Androgen receptor signalling, Castration-resistant prostate cancer (CRPC), Drug resistance (primary and acquired).