Although mortality from prostate cancer has declined over the past 20 years as a 
result of early detection and treatment, the 5-year survival rate for men with 
prostate cancer who develop metastatic disease is only 29%. Current treatment 
options for metastatic castration-recurrent prostate cancer (mCRPC) are 
associated with toxicity and a limited durable response; therefore, additional 
lines of efficacious and minimally toxic therapy are needed. Olaparib, a 
poly(adenosine 5'-diphosphate) ribose polymerase (PARP) inhibitor, received a 
U.S. Food and Drug Administration breakthrough therapy designation in January 
2016 for the treatment of patients with BRCA1/2 or ATM gene-mutated mCRPC based 
on results of a compelling phase II trial of olaparib in patients with advanced 
castration-resistant prostate cancer (TOPARP-A). This study found that men with 
mCRPC and genetic mutations in DNA damage repair genes had an overall response 
rate of nearly 90% with olaparib treatment. In this review, we describe current 
therapies for mCRPC, the rationale for anti-PARP therapies, the pharmacology of 
olaparib for prostate cancer, clinical trials of olaparib for mCRPC, our 
clinical experience with olaparib for prostate cancer at a comprehensive cancer 
center, and future directions of olaparib for the treatment of mCRPC. Olaparib 
may constitute a promising treatment to prolong survival in patients with mCRPC, 
with an acceptable adverse effect profile. As the role of PARP inhibition in 
prostate cancer and other malignancies becomes further elucidated, olaparib may 
be shown to be beneficial for other patient populations.