PARP inhibitors and metastatic castration-resistant prostate cancer: uture directions and pitfalls

PARP inhibitors (PARPi) gained major interest among prostate cancer researchers in the last few years, thanks to the outstanding results coming from the PROfound an TRITON2 studies. Following that, PARPi gained approval also in metastatic, castration-resistant prostate cancer (mCRPC) with mutations in homologous repair (HR) - related genes. Nevertheless, some questions still remain unanswered concerning the management of drug resistance and PARPi-sensitivity in patients harboring alterations in various DNA damage response (DDR) related genes, not only BRCA1 and BRCA2. In this perspective article we focus on the key issues concerning PARPi in mCRPC, specifically those related to drug sensitivity and resistance mechanisms, exploring the possible role of combination therapeutic approaches and trying to depict potential future addresses in translational oncology research.

Automated summary

PARP inhibitors have gained approval in metastatic castration-resistant prostate cancer (mCRPC) with mutations in homologous repair (HR)-related genes, but questions remain regarding drug resistance and PARPi-sensitivity in patients with alterations in various DNA damage response (DDR) related genes. This perspective article focuses on key issues related to PARP inhibitors in mCRPC, exploring potential combination therapeutic approaches and future directions in translational oncology research.