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Cancers 2019, 11(3), 352; https://doi.org/10.3390/cancers11030352

BRCA2 and Other DDR Genes in Prostate Cancer

1
Prostate Cancer Clinical Research Unit, Spanish National Cancer Research Center, 28029 Madrid, Spain
2
CNIO-IBIMA Genitourinary Cancer Research Unit, Institute of Biomedical Research in Malaga (IBIMA), 29010 Málaga, Spain
3
Programs of Molecular Mechanisms and Experimental Therapeutics in Oncology (ONCOBell), and Cancer Therapeutics Resistance (ProCURE), Catalan Institute of Oncology, Bellvitge Institute for Biomedical Research, L’Hospitalet de Llobregat, 08908 Barcelona, Spain
4
Vall d’Hebron Institute of Oncology, Vall d’Hebron University Hospital, 08035 Barcelona, Spain
5
Medical Oncology Department, Hospital Universitario Quironsalud Madrid, 28223 Madrid, Spain
*
Author to whom correspondence should be addressed.
Received: 18 January 2019 / Revised: 11 February 2019 / Accepted: 4 March 2019 / Published: 12 March 2019
(This article belongs to the Special Issue BRCA Mutations and Cancer)
Full-Text   |   PDF [253 KB, uploaded 12 March 2019]

Abstract

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. View Full-Text
Keywords: BRCA2; DNA damage and repair; DDR; prostate cancer; PARP inhibitors BRCA2; DNA damage and repair; DDR; prostate cancer; PARP inhibitors
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Nombela, P.; Lozano, R.; Aytes, A.; Mateo, J.; Olmos, D.; Castro, E. BRCA2 and Other DDR Genes in Prostate Cancer. Cancers 2019, 11, 352.

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