Germline and Somatic Defects in DNA Repair Pathways in Prostate Cancer

Recent studies have provided a better understanding of the molecular underpinnings of prostate cancer. Alterations in genes encoding for proteins involved in the different pathways in charge of preserving genomic integrity and repairing DNA damage are common in prostate cancer, particularly in late-stage disease. Generally, these alterations would confer a survival advantage for tumors, resulting in a more aggressive phenotype. However, DNA repair defects can also represent a vulnerability for tumors that can be exploited therapeutically, offering the possibility of precision medicine strategies. Moreover, many of these mutations are linked to hereditary risk for cancers; hence, identification of DNA repair mutations could also be relevant for cancer prevention and screening in healthy individuals, including relatives of prostate cancer patients. In this chapter, we summarize current knowledge about the prevalence of different DNA repair gene alterations across different stages of prostate cancer and review the clinical relevance of such events in terms of prognosis and treatment stratification.