DNA修复与自噬在胶质瘤替莫唑胺耐药中的作用机制研究进展

Research progress in the mechanisms of DNA repair and autophagy in resistance of gliomas to temozolomide

摘要:

替莫唑胺（TMZ）作为一种新型的口服烷化剂，是现今胶质瘤化学治疗的一线用药。TMZ耐药性涉及多种机制。包括O6-甲基鸟嘌呤DNA甲基转移酶（MGMT）、错配修复（MMR）及碱基切除修复（BER）等在内的DNA修复机制可以修复TMZ引起的DNA损伤，从而降低TMZ敏感性。此外，自噬对于TMZ耐药性也有着复杂的作用。该文对TMZ耐药机制以及为改善耐药性而开发的一些治疗策略的最新研究进展进行综述。

Abstract:

Temozolomide (TMZ), as a new oral alkylating agent, is a first-line drug for glioma chemotherapy nowadays. The drug resistance to TMZ involves multiple mechanisms, among which the DNA repair mechanism, including O6-methylguanine-DNA methyltransferase, mismatch repair, and base excision repair, can repair DNA damage caused by TMZ, thereby reducing the sensitivity to TMZ; in addition, autophagy also has a complicated effect on the drug resistance to TMZ. This article reviews the latest research progress in the mechanisms of drug resistance to TMZ and various therapeutic strategies developed to reverse the resistance.