替莫唑胺在恶性胶质瘤治疗方面的研究进展

Research progress of temozolomide in the treatment of malignant glioma

恶性胶质瘤是常见的颅内原发性肿瘤,替莫唑胺(TMZ)是一种临床上用于治疗恶性神经胶质瘤的DNA-烷化剂药物。DNA修复蛋白O^(6)-甲基鸟嘌呤-DNA-甲基转移酶(O^(6)-methylguanine-DNA methyltransferase,MGMT)的表观遗传沉默是TMZ治疗恶性胶质瘤的重要靶点,因此,对于缺乏MGMT启动子甲基化的肿瘤患者TMZ不能发挥有效的治疗效果。同时,研究表明通过基因治疗降低MGMT水平可显著增加TMZ的治疗作用,降低治疗抗性。因此,本研究对TMZ在恶性胶质瘤治疗的作用机制和化学抗性进行综述,以期为今后TMZ的临床应用提供理论依据。

Malignant glioma is a common primary intracranial tumor,and temozolomide(TMZ)is a DNAalkylating agent drug used clinically to treat malignant glioma.The epigenetic silencing of DNA repair protein O^(6)-methylguanine-DNA methyltransferase(MGMT)is an important target of TMZ in the treatment of malignant glioma.Therefore,TMZ cannot play an effective therapeutic role in the treatment of tumor patients lacking methylation of MGMT promoter.At the same time,research shows that reducing the level of MGMT through gene therapy can significantly increase the therapeutic efficacy of TMZ and reduce the therapeutic resistance.Therefore,the mechanism of action and chemical resistance of TMZ in the treatment of malignant glioma is reviewed in this paper,so as to provide a theoretical basis fo r the clinical application of TMZ in the future.