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In prostate cancer, blocking androgen signalling makes cells more dependent on PARP, and PARP inhibition weakens AR signalling in turn.
This combination pairs PARP inhibitors with Androgen deprivation & AR pathway inhibitors in Prostate cancer. The mechanism is bidirectional cross-talk: the androgen receptor regulates DNA repair genes and PARP is an AR co-factor, so blocking androgen signalling makes cells more dependent on PARP while PARP inhibition weakens AR signalling, creating synergy that extends beyond BRCA-mutant tumours and linking the DNA damage response & homologous recombination and Androgen receptor signalling pathways. Three phase 3 trials support it: PROpel (Olaparib with abiraterone), TALAPRO-2 (Talazoparib with enzalutamide, which showed an overall survival benefit) and MAGNITUDE (Niraparib with abiraterone). The benefit is largest in HRR-mutant tumours and present in some all-comer analyses.
Shares Talazoparib, Androgen deprivation & AR pathway inhibitors, PARP inhibitors, Prostate cancer.
Shares Niraparib, Androgen deprivation & AR pathway inhibitors, PARP inhibitors, Prostate cancer.
Shares Androgen deprivation & AR pathway inhibitors, PARP inhibitors, Olaparib, Prostate cancer.
Shares Talazoparib, Niraparib, PARP inhibitors, Olaparib.
Shares PARP inhibitors, Olaparib, Prostate cancer.
Shares Niraparib, PARP inhibitors, Prostate cancer.
Shares Niraparib, PARP inhibitors.
Shares PARP inhibitors, Olaparib, Prostate cancer.