胶质母细胞瘤对替莫唑胺耐药机制的研究进展

Research progress on the mechanism of temozolomide resistance in glioblastoma

小分子烷化剂替莫唑胺(temozolomide,TMZ)是胶质母细胞瘤(glioblastoma,GBM)的一线治疗药物。然而,由于O-6-甲基鸟嘌呤-DNA甲基转移酶(O-6-methylguanine-DNA methyltransferase,MGMT)和DNA修复途径激活等因素介导的TMZ耐药,很多患者难以从TMZ治疗中获益。文章将从多个角度阐述TMZ耐药的详细分子机制,探讨缓解TMZ耐药以及增强TMZ疗效的新型治疗策略和潜在药物分子,希望为临床缓解胶质瘤患者的TMZ耐药问题提供参考。

The small molecule alkylating agent temozolomide(TMZ)is commonly used as a frontline therapy for glioblastoma(GBM).However,there are certain factors,such as the presence of O-6-methylguanine-DNA methyltransferase(MGMT)and activated DNA repair pathways,that can lead to resistance to TMZ,thereby limiting its effectiveness.This paper aims to comprehensively review the detailed molecular mechanisms of TMZ resistance,discuss innovative therapeutic strategies to overcome resistance,and explore potential drugs that may enhance the efficacy of TMZ.Ultimately,our goal is to provide valuable insights into clinical approaches for mitigating TMZ resistance in GBM patients.