TY - JOUR T1 - Treatment of Metastatic Castration-resistant Prostate Cancer: Are PARP Inhibitors Shifting the Paradigm? JF - Anticancer Research JO - Anticancer Res SP - 4687 LP - 4695 DO - 10.21873/anticanres.15282 VL - 41 IS - 10 AU - NAOHIRO FUJIMOTO AU - KENICHI HARADA AU - MASAKI SHIOTA AU - IKKO TOMISAKI AU - AKINORI MINATO AU - YUJIRO NAGATA AU - RIEKO KIMURO AU - MIRII HARADA AU - MASATO FUJISAWA Y1 - 2021/10/01 UR - http://ar.iiarjournals.org/content/41/10/4687.abstract N2 - Remarkable developments in the treatment of metastatic castration-resistant prostate cancer (mCRPC) have been achieved over the past decade. Although targeting the novel androgen receptor axis and using chemotherapeutic agents have improved survival, mCRPC is still a lethal disease. A better molecular characterization of cancer resulted in the determination of the important role of homologous recombination repair (HRR) genes in cancer development, and poly (ADP-ribose) polymerase (PARP) is one of the most attractive therapeutic targets. Recent clinical studies have demonstrated that PARP inhibitors significantly improve oncological outcomes in patients with mCRPC harboring BRCA mutations, and PARP inhibitors are becoming a standard of care for these patients. However, not only PARP inhibitors, but also chemotherapeutic agents such as platinum agents, taxanes, and radium-223 are active in HRR gene mutation carriers, and platinum sensitivity may predict the efficacy of PARP inhibitors for mCRPC. The combination of PARP inhibitors with other anti-cancer agents may overcome resistance mechanisms against PARP inhibitors and lead to survival benefits. Appropriate treatment sequences and combinations may change the therapeutic landscape of DNA repair deficient mCRPC. ER -