He Yu-Jun, Liu Rui-Huan, Ning Cheng-Qing, Yu Nie-Fang
School of Pharmaceutical Sciences, Central South University, Changsha 410013, China.
Yao Xue Xue Bao. 2013 May;48(5):655-60.
The poly(ADP-ribose) polymerases (PARPs) is an important group of enzymes in DNA repair pathways, especially the base excision repair (BER) for DNA single-strand breaks (SSBs) repair. Inhibition of PARP in DNA repair-defective tumors (like those with BRAC1/2 mutations) can lead to cell death and genomic instability, what is so called "synthetic lethality". Currently, PARP inhibitors combined with cytotoxic chemotherapeutic agents in the treatment of BRCA-1/2 deficient cancers are in the clinical development. In this review, we will be focused on the development of combination application of PARP inhibitors with other anticancer agents in clinical trials.
聚（ADP - 核糖）聚合酶（PARPs）是DNA修复途径中的一组重要酶，尤其在DNA单链断裂（SSB）修复的碱基切除修复（BER）中发挥作用。在DNA修复缺陷的肿瘤（如那些具有BRAC1/2突变的肿瘤）中抑制PARP可导致细胞死亡和基因组不稳定，即所谓的“合成致死性”。目前，PARP抑制剂与细胞毒性化疗药物联合用于治疗BRCA - 1/2缺陷型癌症正处于临床开发阶段。在本综述中，我们将重点关注PARP抑制剂与其他抗癌药物联合应用在临床试验中的进展。
