拓扑异构酶1及其喜树碱类抑制剂的临床研究进展

Topoisomerase 1 and its camptothecin inhibitors in clinic:research advances

DNA拓扑异构酶1(Top 1)是一种重要的核酶,在DNA复制、转录、重组、修复、染色质组装和染色体分离等细胞代谢过程中,控制和修饰DNA拓扑结构。而且,Top1在多种肿瘤细胞中均过度表达。Top 1作为抗肿瘤药物靶点的确认,促进了新型抗肿瘤药物的发展。目前,研究最多的Top 1抑制剂主要是喜树碱类,已有3个喜树碱类药物上市(拓扑替康、伊立替康和贝洛替康)。本文对Top 1结构和功能的最新研究结果及其喜树碱类抑制剂的近期临床研究进展进行综述。

DNA topoisomerase 1（Top 1） is an essential human enzyme that controls and modifies the topological state of DNA in many cellular metabolic processes,such as replication,transcription,recombination,repair,chromatin assembly and chromosome segregation.Besides,Top 1 is overexpressed in human cancers.Identification of Top 1 as a viable target of anticancer drugs has led to the development of new anticancer agents.Up to now,three camptothecin derivatives,topotecan,irinotecan,and belotecan,have been approved for clinical treatment of cancers.This article provides a brief review on the structure and function of Top 1,and summarizes the research advances on the camptothecin inhibitors in clinic.