Mechanisms of PARP inhibitor sensitivity and resistance

被引：362

作者：

D'Andrea, Alan D. ^{[1
,2
]}

机构：

[1] Dana Farber Canc Inst, Dept Radiat Oncol, HIM 243,450 Brookline Ave, Boston, MA 02215 USA

[2] Dana Farber Canc Inst, Ctr DNA Damage & Repair, Boston, MA 02215 USA

来源：

DNA REPAIR | 2018年 / 71卷

关键词：

BRCA1/2; PARPI; Homologous recombination; Replication fork; REPLICATION FORKS; BREAST CANCERS; DNA-REPAIR; RECOMBINATION; BRCA2; STABILIZATION; POLYMERASE; MUTATIONS; RESECTION; PROTEIN;

D O I：

10.1016/j.dnarep.2018.08.021

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

BRCA1 and BRCA2 deficient tumor cells are sensitive to inhibitors of Poly ADP Ribose Polymerase (PARP1) through the mechanism of synthetic lethality. Several PARP inhibitors, which are oral drugs and generally well tolerated, have now received FDA approval for various ovarian cancer and breast cancer indications. Despite their use in the clinic, PARP inhibitor resistance is common and develops through multiple mechanisms. Broadly speaking, BRCA1/2-deficient tumor cells can become resistant to PARP inhibitors by restoring homologous recombination (HR) repair and/or by stabilizing their replication forks. Here, we review the mechanism of PARP inhibitor resistance.

引用

页码：172 / 176

页数：5

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