In May 2020, the poly(ADP-ribose) polymerase (PARP) inhibitors rucaparib and olaparib were Food and Drug Administration approved for the management of metastatic castration-resistant prostate cancers. Rucaparib was approved for tumors that harbor alterations in BRCA1 and BRCA2 following progression on chemotherapy and androgen receptor-directed therapy, whereas olaparib was approved for tumors that harbor alterations in a broader range of DNA damage repair genes following progression on androgen receptor-directed therapy. Loss-of-function mutations in genes such as BRCA1 and BRCA2 increase reliance on PARP-mediated mechanisms of DNA repair, and inhibition of this pathway results in the accumulation of lethal levels of DNA damage. This dependence is advantageous in the management of prostate cancer, as mutations in DNA damage repair genes are frequent. This review summarizes the role of PARP in cell homeostasis, methods of targeting PARP in cancer cells, and current clinical trials in the management of advanced prostate cancer with PARP inhibitors.
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