胶质瘤对替莫唑胺的耐药性机制研究进展  

Research advances on the mechanism of glioma resistance to temozolomide

作　　者：徐小珊[1] 涂艳阳[1] 

机构地区：[1]第四军医大学唐都医院实验外科,陕西西安710038

出　　处：《转化医学电子杂志》2017年第7期55-60,共6页E-Journal of Translational Medicine

基　　金：国家自然科学基金(81572983);陕西省社会发展科技攻关项目(2015SF027);唐都医院创新发展基金资助项目(2016JCYJ013)

摘　　要：目前,临床上针对胶质瘤的标准治疗方案为手术切除联合放化疗.替莫唑胺(TMZ)是一种新型的口服烷化剂,由于它能穿过血脑屏障到达患者的肿瘤病灶,发挥持久的治疗作用,被广泛用于胶质瘤的联合治疗.但是,由于替莫唑胺耐药性的产生,使得患者的生存期缩短,预后差.这种耐药性产生的机制十分复杂,主要包括DNA修复酶的激活,表皮生长因子受体(EGFR)和半乳凝素-1的过表达,p53,双微体2(Mdm2),磷酸酶及张力蛋白同源基因(PTEN)以及miRNAs的异常调控.因此,探讨胶质瘤对替莫唑胺耐药性的产生机制以及如何有效地降低替莫唑胺耐药性,提高其疗效已经成为一个迫切需要解决的问题.本文将介绍GBM对TMZ耐药的主要机制,以期为胶质瘤的临床治疗提供充足的理论依据.At present, the standard treatment strategy for glioma is surgical resection eombined with radiotherapy and chemothera- py. Temozolomide （TMZ） is a novel oral alkylating agent that is widely used in the combined treatment of gliomas. Beeanse it could pass through the blood-brain barrier to reach the patient＇s tumor lesions and play a lasting therapeutic effect. However, the survival time of glioma patients is short and the prognosis is poor due to the drug resistance of temozolomide. The mechanism of this drug resistance is very complex, including the activation of DNA repair enzymes, the overexpression of EGFR （ epidermal growth factor receptor） and galactinin-1 , the abnormal regulation of p53, Mdm2 （mouse bimodal 2）, PTEN （phosphatase and tonic protein homologs） and miRNAs. Therefore, we need a better un- derstanding of the mechanism of glioma resistance to temozolo- mide, which will help us to find a solution to reduce the resistance of temozolomide and improve the efficacy of chemotherapy drugs.

关 键 词：替莫唑胺 耐药性 胶质瘤 

分 类 号：R739.41[医药卫生—肿瘤]