The Emerging Role of PARP Inhibitors in the Treatment of Prostate Cancer

Poly (ADPribose) polymerase (PARP) is a critical DNA repair enzyme involved in DNA single-strand break repair through the base excision repair pathway. PARP inhibitors have been shown to sensitize tumors to DNA-damaging agents and selectively kill homologous recombination repair-defective cancers, such as those arising in BRCA1 and BRCA2 mutation carriers. In addition to its well-documented role in DNA damage repair (DDR), emerging evidence has indicated that PARP1 plays an important role in mediating the transcriptional activities of androgen receptor (AR) and ETS gene rearrangement in prostate cancer. Preclinical and clinical research suggested that the activity of PARP inhibitors is not limited to those with BRCA mutations. PARP inhibitors may have activity in cancers deficient in other DNA repair genes or signaling pathways that mitigate DNA repair.