Targeting DNA Repair Defects for Precision Medicine in Prostate Cancer

被引：18

作者：

Athie, Alejandro ^{[1
]}

Arce-Gallego, Sara ^{[1
]}

Gonzalez, Macarena ^{[1
,2
]}

Morales-Barrera, Rafael ^{[1
,2
]}

Suarez, Cristina ^{[1
,2
]}

Casals Galobart, Teresa ^{[1
]}

Hernandez Viedma, Gonzalo ^{[1
]}

Carles, Joan ^{[1
,2
]}

Mateo, Joaquin ^{[1
,2
]}

机构：

[1] Vall dHebron Inst Oncol VHIO, Cellex Ctr, Prostate Canc Translat Res Grp, Natzaret 115-117, Barcelona 08035, Spain

[2] Vall dHebron Univ Hosp, Dept Med Oncol, Barcelona, Spain

来源：

CURRENT ONCOLOGY REPORTS | 2019年 / 21卷 / 05期

关键词：

DNA damage repair; Prostate cancer; PARP; BRCA1/2; Androgen receptor; Genomic alterations; Personalized medicine; POLY(ADP-RIBOSE) POLYMERASE; MUTATIONAL LANDSCAPE; MAINTENANCE THERAPY; GERMLINE MUTATIONS; MISMATCH-REPAIR; TUMORS; MEN; BLOCKADE; OLAPARIB; BRCA2;

D O I：

10.1007/s11912-019-0790-6

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Purpose of ReviewGenomic studies of localized and metastatic prostate cancer have identified a high prevalence of clinically actionable alterations including mutations in DNA repair genes. In this manuscript, we review the current knowledge on DNA repair defects in prostate cancer and provide an overview of how these alterations can be targeted towards a personalized prostate cancer management.Recent FindingsTwenty to 25% of metastatic prostate cancers harbor defects in DNA repair genes, most commonly in the homologous recombination genes. These defects confer increased sensitivity to platinum chemotherapy or poly (ADP-ribose) polymerase (PARP) inhibitors. Recent trials also support a synergistic effect of combining these therapies with androgen receptor-targeting agents. Identification of mismatch-repair defects could result in defining a prostate cancer population who may benefit from immune checkpoint inhibitors. These data have implications for family testing and early diagnosis, as many of these mutations are linked to inherited risk of prostate cancer.SummaryThe DNA damage repair pathways are clinically relevant in prostate cancer, being a target for precision medicine; combination with standard-of-care androgen receptor (AR)-targeting agents may be synergistic.

引用

页数：10

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