PARP Inhibitors in Prostate Cancer – Understanding the Current Landscape

Abstract

Poly (ADP [adenosine diphosphate]-ribose) polymerase inhibitors (PARPi) are a current standard of care treatment option for patients with metastatic castration resistant prostate cancer (mCRPC), defined as prostate cancers that continue to progress despite treatment with the usual first-line androgen-deprivation therapies. PARPi’s function by targeting faulty homologous recombination repair pathways that result in cytotoxic double strand DNA break (DSB) accumulation in prostate cancer cells. While the efficacy of PARPi’s as a monotherapy option in mCRCP has been demonstrated clinically, the added utility of PARPi’s in combination with other anti-cancer agents is still being explored. This article will review the scientific rationale behind PARP-inhibitors, discuss the germline and somatic mutation testing critical to identifying predictive biomarkers for PARPi efficacy, and present the currently approved PARPi combination therapies and their indications. This review will also examine the incidence and management of PARPi toxicity, summarize ongoing trials, and propose areas of future study.