DNA损伤修复与肺癌顺铂耐药机制的研究进展

肺癌是目前世界上致死率最高的恶性肿瘤,化疗是治疗的主要手段之一,肺癌的化疗是以铂类为基础的联合化疗,其中,顺铂是有效并广泛应用的一线药物,但是由于耐药问题的存在使其疗效不尽如人意。顺铂是一种细胞周期非特异性细胞毒药物,其主要作用靶点是DNA,因此DNA损伤修复功能的异常是顺铂耐药的主要机制之一。本文主要综述了与肺癌顺铂耐药相关的DNA损伤修复异常,包括核苷酸切除修复异常、碱基错配修复异常、DNA双链断裂损伤修复异常及跨损伤修复。

Advances of DNA damage repair and Cisplatin resistance mechanisms in lung cancer

Lung cancer is the most common cause of death from cancer worldwide per year. Platinum-based combination chemotherapy is a main treatment of lung cancer. Cisplatin is adopted widely and used effectively in the first-line chemotherapy. Unfortunately, development of cisplatin resistance is a major obstacle to the success of lung caner. Cisplatin is a cell-cycle-non-specific cytotoxic drugs and its main target is DNA. Thus, defective DNA damage repair is one of the main mechanisms of cisplatin resistance. In this review, we will focus on the defective DNA damage repair in cisplatin resistance of lung cancer including nucleotide excision repair, DNA mismatch repair, DNA double-strand break repair and translesion synthesis.