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碱基切除修复与抗肿瘤药物耐药
         
Base excision repair and antineoplastic drug resistance

摘    要
化疗是目前临床上治疗肿瘤的主要方法之一,抗肿瘤药物耐药则是导致肿瘤治疗失败的重要原因之一。多种化疗药物抗肿瘤的主要机制是引起DNA损伤,进而导致肿瘤细胞凋亡;因此,DNA修复功能状态与抗肿瘤药物疗效有着直接的关系。目前,已知有4种主要的DNA修复途径:碱基切除修复(base excision repair,BER)、核苷酸切除修复(nucleotide excision repair,NER)、错配修复(mismatch repair,MMR)和双键断裂修复(double strand break repair,DSBR)。其中,BER是主要的DNA修复机制之一,其修复功能异常与抗肿瘤药物耐药有着密切的联系。近年来,以BER为靶点开发了多种逆转耐药的药物或方法。本文将简要综述相关的研究进展,深入探讨抗肿瘤药物耐药的发生机制及防治措施。
标    签 肿瘤   DNA修复   抗肿瘤药物   抗药性   碱基切除修复   Neoplasms   DNA repair   Antineoplastic agents   Drug resistance   Base excision repair  
 
Abstract
Chemotherapy is one of the main methods to treat malignant tumors in clinicalpractice. Resistance to antineoplastic agents is one of the important reasons for treatment failure. Theantineoplastic mechanism of various chemotherapeutic agents is to cause DNA damage, then resultin apoptosis of tumor cells. It is suggested that the function of DNA repair is directly associated withthe efficacy of antineoplastic agents. Current studies suggest that there are four major DNA repairpathways including BER (base excision repair), NER (nucleotide excision repair), MMR (mismatch repair)and DSBR (double strand break repair). Of these four pathways, BER is one of the main mechanisms ofDNA repair and its malfunction is closely related to the resistance to antineoplastic agents. Recently,many kinds of agents and strategies targeting BER have been developed to reverse chemoresistance. Thisreview summarizes the progress in research in this area and discusses the mechanism of resistance toantineoplastic agents and the potential preventive and therapeutic strategies.

中图分类号 R730.53   DOI 10.3781/j.issn.1000-7431.2013.03.016

 
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基金项目 国家重点基础研究发展计划(973计划)(编号:2010CB529402)

收稿日期 2012/12/17

修改稿日期 2013/1/18

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引用该论文: KUANG Li-shan,WANG Yu-liang,ZHOU Xiang-dong. Base excision repair and antineoplastic drug resistance[J]. Tumor, 2013, 33(3): 294~298
况里杉,王宇亮,周向东. 碱基切除修复与抗肿瘤药物耐药[J]. 肿瘤, 2013, 33(3): 294~298


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