Poly (ADP-ribose) polymerase inhibitors (PARPi) are a unique class of 
antineoplastic agents that function by inducing synthetic lethality. Synthetic 
lethality occurs when PARPi and either another agent or an underlying genetic 
alteration together lead to overwhelming DNA damage and ultimately cell death. 
PARPi first showed promise as a cancer therapy in patients with BRCA1/2 
mutations and have become part of standard treatment for breast and ovarian 
cancer. In prostate cancer, two PARPi, rucaparib and olaparib, have been FDA 
approved for the treatment of metastatic castration-resistant prostate cancer 
(mCRPC). While both agents are approved for tumors with BRCA1/2 alterations, for 
olaparib the indication is also expanded to patients with 12 other homologous 
recombination deficiency (HRD) gene alterations including ATM and PALB2. PARPi 
differ in their pharmacokinetics and pharmacodynamics, and additional studies 
are being conducted with niraparib, veliparib, and talazoparib in prostate 
cancer. While PARPi are fairly well tolerated, common toxicities include 
hematologic (anemia/thrombocytopenia) and gastrointestinal effects 
(nausea/vomiting). Ongoing studies are being conducted combining PARPi with 
other agents in patients with and without HRD alterations. Early data are 
promising for the combination of PARPi with second-generation antiandrogens and 
with immunotherapy. As additional trials are developed and reported, the hope is 
that the patient population who may benefit from PARPi will continue to expand.