(UroToday.com) In 2016, Colin Pritchard and colleagues reported that mutations in DNA-damage repair genes, particularly homologous recombination repair genes, were relatively common among patients with advanced metastatic castration-resistant prostate cancer (mCRPC). This opened the potential for targeted therapy using poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors which lead to an accumulation of DNA single-stranded breaks which have particularly profound clinical consequences for patients who lack standard homologous recombination repair mechanisms as a result of mutations in important genes in this pathway, including BRCA1 and BRCA2. Early data supporting the use of the PARP inhibitor olaparib from the TOPARP-A trial found improvements in progression-free and overall survival in men with heavily pre-treated mCRPC.