BRCA2 and Other DDR Genes in Prostate Cancer

被引：80

作者：

Nombela, Paz ^{[1
]}

Lozano, Rebeca ^{[1
,2
]}

Aytes, Alvaro ^{[3
,4
]}

Mateo, Joaquin ^{[5
]}

Olmos, David ^{[1
,2
]}

Castro, Elena ^{[1
,6
]}

机构：

[1] Spanish Natl Canc Res Ctr, Prostate Canc Clin Res Unit, Madrid 28029, Spain

[2] Inst Biomed Res Malaga IBIMA, CNIO IBIMA Genitourinary Canc Res Unit, Malaga 29010, Spain

[3] Bellvitge Inst Biomed Res, Catalan Inst Oncol, Program Mol Mech & Expt Therapeut Oncol ONCOBell, Barcelona 08908, Spain

[4] Bellvitge Inst Biomed Res, Catalan Inst Oncol, Program Canc Therapeut Resistance ProCURE, Barcelona 08908, Spain

[5] Vall dHebron Univ Hosp, Vall dHebron Inst Oncol, Barcelona 08035, Spain

[6] Hosp Univ Quironsalud Madrid, Dept Med Oncol, Madrid 28223, Spain

来源：

CANCERS | 2019年 / 11卷 / 03期

关键词：

BRCA2; DNA damage and repair; DDR; prostate cancer; PARP inhibitors; CELL-FREE DNA; MUTATION CARRIERS; POLY(ADP-RIBOSE) POLYMERASE; DOSE-ESCALATION; BREAST; REPAIR; MEN; SURVIVAL; RISK; CHEMOTHERAPY;

D O I：

10.3390/cancers11030352

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页数：15

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