While androgen deprivation therapy (ADT) has been the mainstay of treatment for advanced prostate cancer (PCa) leading to initial response and durable remission, incurable castration-resistant prostate cancer (CRPC) invariably develops. Importantly, androgen receptor (AR) activity remains critical for CRPC tumor growth. Despite the significant research advances in PCa biology and development of next-generation antiandrogens, there has been limited progress in the management of CRPC when direct AR-targeted therapies fail. PARP-2, which enhances AR-mediated transcription through interaction with the pioneer factor FOXA, is a druggable target. Targeting PARP-2 may potentially provide an alternative therapeutic approach for AR inhibition without involving AR ligand binding.
