Mechanisms of PARP inhibitor sensitivity and resistance
Mechanisms of PARP inhibitor sensitivity and resistance
复制标题
DOI：
10.1016/j.dnarep.2018.08.021
复制
发表时间：
2018-11-01
期刊：
影响因子：
3.8
通讯作者：
D'Andrea, Alan D.
中科院分区：
文献类型：
--
作者：
D'Andrea, Alan D.
BRCA1和BRCA2缺陷肿瘤细胞通过合成致死性机制对聚ADP核糖聚合酶（PARP1）抑制剂敏感。有几种PARP抑制剂是口服药物，通常耐受性良好，目前已获得FDA批准用于各种卵巢癌和乳腺癌适应症。尽管它们在临床上使用，PARP抑制剂耐药是常见的，并通过多种机制发展。一般来说，brca1 /2缺陷肿瘤细胞可以通过恢复同源重组（HR）修复和/或稳定其复制分叉而对PARP抑制剂产生耐药性。本文就PARP抑制剂耐药机制进行综述。
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.