The role of PARP1 in the DNA damage response and its application in tumor therapy.
The role of PARP1 in the DNA damage response and its application in tumor therapy.
复制标题
PARP1在DNA损伤反应中的作用及其在肿瘤治疗中的应用
DOI：
10.1007/s11684-012-0197-3
复制
发表时间：
2012-06-01
影响因子：
8.1
通讯作者：
Guo, Caixia
中科院分区：
文献类型：
--
作者：
Wang, Zhifeng;Wang, Fengli;Guo, Caixia
单链断裂修复蛋白聚（ADP-核糖）聚合酶1（PARP 1）在体内催化许多关键蛋白的聚（ADP-核糖基）化，因此在多个DNA损伤反应途径中起重要作用，使其成为肿瘤治疗的有希望的靶点。PARP抑制剂的肿瘤抑制作用已经吸引了开发新的癌症治疗的显著兴趣。然而，最近的证据表明，PARP抑制剂在肿瘤治疗中的潜在机制比以前预期的更复杂。本文就PARP 1在DNA损伤反应中的作用及PARP抑制剂在肿瘤治疗中的研究进展作一综述。BRCA缺陷型肿瘤对PARP抑制剂的耐药性也从DNA损伤和修复的角度进行了简要讨论。这些最新的研究进展将为选择可以从PARP抑制剂治疗中获益的患者人群和开发有效的药物组合策略提供信息。
Single-strand break repair protein poly(ADP-ribose) polymerase 1 (PARP1) catalyzes the poly(ADP-ribosyl)ation of many key proteins in vivo and thus plays important roles in multiple DNA damage response pathways, rendering it a promising target in cancer therapy. The tumor-suppressor effects of PARP inhibitors have attracted significant interest for development of novel cancer therapies. However, recent evidence indicated that the underlying mechanism of PARP inhibitors in tumor therapy is more complex than previously expected. The present review will focus on recent progress on the role of PARP1 in the DNA damage response and PARP inhibitors in cancer therapy. The emerging resistance of BRCA-deficient tumors to PARP inhibitors is also briefly discussed from the perspective of DNA damage and repair. These recent research advances will inform the selection of patient populations who can benefit from the PARP inhibitor treatment and development of effective drug combination strategies.