The approval of upfront abiraterone for castration-sensitive prostate cancer and 
the approval of enzalutamide and apalutamide for non-metastatic 
castration-resistant prostate cancer have led to early utilization of potent 
androgen receptor (AR) signaling inhibitors in treating advanced prostate 
cancer. There is an unmet need to develop novel therapies beyond targeting AR 
signaling for metastatic castration-resistant prostate cancer (mCRPC). Poly 
(ADP-ribose) polymerase inhibitors (PARPi) belong to a class of targeted agents 
being developed for the treatment of homologous recombination repair (HRR) 
deficient tumors. Olaparib, rucaparib, niraparib, veliparib, and talazoparib 
were evaluated in early phase trials as a monotherapy for HRR-deficient mCRPC. 
Among them, olaparib and rucaparib have breakthrough designations for 
BRCA1/2-mutated mCRPC. Phase II studies also reported clinical activity of the 
PARPi and abiraterone combination and the PARPi checkpoint inhibitor combination 
in HRR-intact mCRPC. Ongoing phase III trials are testing these combinations as 
frontline or later line treatments for mCRPC. This review summarizes the 
critical clinical data as well as ongoing clinical trials for developing PARPi 
in treating mCRPC.