RT Generic T1 BRCA2 and Other DDR Genes in Prostate Cancer. A1 Nombela, Paz A1 Lozano, Rebeca A1 Aytes, Alvaro A1 Mateo, Joaquin A1 Olmos, David A1 Castro, Elena K1 BRCA2 K1 DDR K1 DNA damage and repair K1 PARP inhibitors K1 prostate cancer AB 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. PB Mdpi SN 2072-6694 YR 2019 FD 2019-03-12 LK http://hdl.handle.net/10668/13709 UL http://hdl.handle.net/10668/13709 LA en NO Nombela P, Lozano R, Aytes A, Mateo J, Olmos D, Castro E. BRCA2 and Other DDR Genes in Prostate Cancer. Cancers (Basel). 2019;11(3):352. Published 2019 Mar 12. NO R.L., A.A., and D.O. were funded by the Instituto de Salud Carlos III (grants CM17/00221 to R.L., PI16/01070 and CP15/00090 to A.A., and PI16/01565 to D.O.). A.A. is supported by grants from the European Association of Urology Research Foundation (EAURF/407003/XH), a Department of Defense Award (W81XWH-18-1-0193), Fundacion BBVA, CERCA Program/Generalitat de Catalunya, and FEDER funds/European Regional Development Fund (ERDF)-A Way to Build Europe. D.O. was funded by grants from the Ministerio de Economía y Empresa (RYC-2015-18625). E.C. and J.M. were supported by Young Investigator Awards from the Prostate Cancer Foundation. J.M. and D.O. were supported by an Impact Award from the Department of Defense US (PC170510P2). DS RISalud RD Jul 7, 2025