Prostate cancer in the era of “Omic” medicine: recognizing the importance of DNA damage repair pathways

Data from recent high-throughput studies analyzing local and advanced prostate cancer have revealed an incredible amount of biological diversity, which has led to the classification of distinct molecular tumor subtypes. While integrating prostate cancer genomics with clinical medicine is still at its infancy, new approaches to treat prostate cancer are well underway and being studied. With the recognition that DNA damage repair (DDR) mutations play an important role in the pathogenesis of this disease, clinicians can begin to utilize genomic information in complex treatment decisions for prostate cancer patients. In this Review, we discuss the role of DDR mutations in prostate cancer, including deficiencies in homologous repair and mismatch repair (MMR), and how this information is revolutionizing the treatment landscape. In addition, we highlight the potential resistance mechanisms that may result as we begin to target these pathways in isolation and discuss potential combinatorial approaches that may delay or overcome resistance.