: Advances in DNA sequencing technology have created a wealth of information 
regarding the genomic landscape of prostate cancer. It had been thought that 
BRCA1 and BRCA2 mutations were associated with only a small fraction of prostate 
cancer cases. However, recent genomic analysis has revealed that germline or 
somatic inactivating mutations in BRCA1 or BRCA2, or other genes involved in the 
homologous recombination (HR) pathway of DNA repair collectively occur in as 
much as 20%-25% of advanced prostate cancers. A synthetic lethal therapeutic 
approach using poly(ADP-ribose) polymerase inhibitor therapy has been developed 
for BRCA mutant- and HR deficient-related cancers (those with "BRCAness") and is 
being studied in multiple clinical trials. This article discusses the current 
understanding of the genomic landscape of prostate cancer, focusing on the 
occurrence of DNA repair mutations and the therapeutic opportunities that this 
presents.
IMPLICATIONS FOR PRACTICE: This review aims to update oncologists about the 
increased understanding of the genomes of prostate cancers and, in particular, 
the prevalence of mutations in DNA repair genes. These observations provide 
potential new therapeutic opportunities for the use of poly(ADP-ribose) 
polymerase inhibitors and other therapies, especially in advanced forms of the 
disease. Of note is the recent U.S. Food and Drug Administration breakthrough 
therapy designation of olaparib for the treatment of BRCA1/2- or ATM-mutated 
metastatic castration-resistant prostate cancer. The implications of this new 
knowledge for clinical practice now and in the future are discussed.