BRCA2 and Other DDR Genes in Prostate Cancer

Abstract

BRCA2; DDR; Prostate cancer

BRCA2; DDR; Càncer de pròstata

BRCA2; DDR; Cáncer de próstata

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.

Supported by grants CM17/00221, PI16/01070, CP15/00090 and PI16/01565 from the Instituto de Salud Carlos III, PC170510P2 from the U.S. Department of Defense, W81XWH-18-1-0193 from the U.S. Department of Defense, RYC-2015-18625 from the Ministerio de Economía y Competitividad and Young Investigator Awards from the Prostate Cancer Foundation