替莫唑胺治疗胶质母细胞瘤耐药机制的研究进展

Research Progress on Resistance Mechanisms of Temozolomide in Treatment of Glioblastoma

关键词:  胶质母细胞瘤  化疗  替莫唑胺  耐药机制

Key words:  glioblastoma  chemotherapy  temozolomide  resistance mechanisms

摘要:

胶质母细胞瘤（glioblastoma，GBM）是中枢神经系统最常见的原发性肿瘤，它恶性程度高、侵袭性强、易复发、预后差。目前治疗主要以手术切除为主，术后辅以放疗和化疗。替莫唑胺（temozolomide，TMZ）是治疗GBM的临床一线化疗药物，而GBM对TMZ的耐药性是导致其临床治疗失败的主要原因。目前GBM对TMZ的耐药机制主要涉及MicroRNA、DNA损伤修复机制、胶质瘤干细胞学说、肿瘤微环境、肿瘤细胞自噬、信号通路异常等几个方面。本文就近年来TMZ治疗GBM的耐药机制进行了综述，同时探讨了克服GBM对TMZ耐药性的主要策略。

Abstract:

Glioblastoma(GBM) is the most common malignancy of primary central nervous system in adults. It is considered as the high degree of malignancy with strong invasiveness and easy to relapse, in which the treatment is rather difficult. Gold-standard treatments of GBM include tumor resection, radiotherapy and chemotherapy. Temozolomide(TMZ) is the first-line clinical chemotherapy drug for GBM, and the drug resistance of GBM to TMZ is the main cause leading to the failure of its clinical treatment. At present, the drug resistance mechanisms of TMZ in treatment of GBM mainly include:MicroRNA, DNA repair pathways, cancer stem cells, tumor microenvironment, autophagy of tumor cells and deregulated signalling pathways. This review summarizes the mechanisms of TMZ in treatment of GBM in recent years, and the potential overcoming strategies are discussed.