多腺苷二磷酸核糖聚合酶抑制剂抗肿瘤的研究进展-药学学报.pdfVIP

药学学报 Acta Pharmaceutica Sinica 20 13, 48 (5): 655 660 ·655 · 多腺苷二磷酸核糖聚合酶抑制剂抗肿瘤的研究进展 何裕军, 刘瑞环, 宁澄清, 余聂芳* ( 中南大学药学院, 湖南 长沙 4 100 13) 摘要: 多腺苷二磷酸核糖聚合酶[poly(ADP-ribose) polymerases, PARPs] 在DNA 修复途径中起着至关重要的 作用。近年的研究表明, 根据 “合成致死”机制, 通过抑制PARP 活性, 可以有效增强BRCA-1/2 缺陷的肿瘤细 胞对化疗药物的敏感性, 导致肿瘤细胞凋亡。在以PARP 为靶点的 物研究中, 无论是单一用 还是与化疗药物 联合用 , PARP 抑制剂都显示出喜人的 肿瘤效果。本文将针对PARP 抑制剂在多种肿瘤治疗中的联合用药作 一综述。 关键词: 多ADP 核糖聚合酶抑制剂; 合成致死; 肿瘤; 联合用 中图分类号: R9 16 文献标识码: A 文章编号: 0513-4870 (20 13) 05-0655-06 Research progresses of the PARP inhibitors for the treatment of cancer * HE Yu-j un, LIU Rui-huan, NING Cheng-qing, YU Nie-fang (School of Pharmaceutical Sciences, Central South University, Changsha 410013, China ) Abstract : 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. Key words: PARP inhibitor; synthetic lethality; anticancer; combination therapy 化疗是恶性肿瘤的主要治疗手段之一,