Germline and somatic aberrations in DNA damage repair (DDR) genes are more prevalent in
prostate cancer than previously recognized, with BRCA2 as the most commonly altered gene. Germline mutations in BRCA2 have been linked to poor prognosis when patients are managed under the protocols currently approved for
prostate cancer. The impact of germline mutations in other DDR genes beyond BRCA2 remain unclear. Importantly, a quarter of
prostate cancer patients identified as germline mutation carriers lack a family history of
cancer. The clinical implications of somatic DDR defects are yet to be elucidated.
Poly ADP-ribose polymerase (
PARP) inhibitors and
platinum-based
chemotherapy have proven to be effective in the treatment of other
tumor types linked to BRCA1 and BRCA2 alterations and several trials are currently evaluating their efficacy in
prostate cancer. Here, we summarize the available evidence regarding the prevalence of somatic and germline DDR defects in
prostate cancer; their association with clinical outcomes; the trials assessing the efficacy of new
therapies that exploit DDR defects in
prostate cancer and briefly discuss some uncertainties about the most appropriate management for these patients.