替莫唑胺治疗多形性胶质母细胞瘤的化疗耐药机制

Mechanism of chemotherapy resistance of temozolomide in glioblastoma multiforme

胶质瘤约占原发性颅内肿瘤的50%以上,多形性胶质母细胞瘤(GBM)为WHOⅣ级胶质瘤,复发率高,5年生存率不到10%。化疗是GBM综合治疗中的重要一环,而替莫唑胺作为多形性胶质母细胞瘤基石化疗药物在临床广泛应用,然而因其化疗耐药性的存在,严重影响了治疗效果的进一步提高。本文针对目前胶质瘤化疗药物的主要耐药机制:多药耐药、DNA损伤修复机制、凋亡通路异常、胶质瘤干细胞学说等几个方面,结合替莫唑胺药理机制进行分析、总结,希望对提高替莫唑胺在多形性胶质母细胞瘤中的疗效有一定启示。

Gliomas accounts for more than 50% of primary intracranial tumors. Glioblastoma multiforme（ GBM）,as a WHO grade Ⅳ glioma,has high recurrence rate with low5 years survival rate（ 〈 10%）. Chemotherapy is a pivotal part of multimodality therapy for GBM. Temozolomide is the most commonly administrated footstone chemotherapy drug in glioblastoma multiforme,but the chemotherapy resistance limits the improvement of the therapeutic effect for GBM. This paper aims at the main mechanisms of drug resistance of GBM chemotherapy drugs： multidrug resistance,DNA damage repair mechanism,apoptosis pathway abnormalities,glioma stem cell theory,and so on,combines with temozolomide pharmacological mechanism and the mechanisms of drug resistance to analyze and summarize,to improve the efficacy of temozolomide in glioblastoma multiforme treatment.