碱基切除修复与抗肿瘤药物耐药

Base excision repair and antineoplastic drug resistance

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。

Chemotherapy is one of the main methods to treat malignant tumors in clinical practice. Resistance to antineoplastic agents is one of the important reasons for treatment failure. The antineoplastic mechanism of various chemotherapeutic agents is to cause DNA damage, then result in apoptosis of tumor cells. It is suggested that the function of DNA repair is directly associated with the efficacy of antineoplastic agents. Current studies suggest that there are four major DNA repair pathways 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 of DNA 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. This review summarizes the progress in research in this area and discusses the mechanism of resistance to antineoplastic agents and the potential preventive and therapeutic strategies.