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神经胶质瘤是较常见的颅内恶性肿瘤,手术、放疗及辅以替莫唑胺(TMZ)的化疗已成为欧洲的一线治疗措施。TMZ烷化DNA产生O6-甲基鸟嘌呤(O6-meG)、N7-甲基鸟嘌呤(N7-meG)、N3-甲基腺嘌呤(N3-meA)等DNA加合物而发挥抗癌作用。TMZ的抗癌作用主要是由O6-meG介导的,但肿瘤细胞DNA修复系统中O6-meG-DNA甲基转移酶(MGMT)可以修复O6-meG而导致TMZ的疗效降低,同时TMZ抗癌作用需要完整的碱基错配修复(MMR)系统参与。N7-meG主要被碱基切除修复(BER)系统修复。TMZ在临床的治疗效果有很大的个体差异,固有的或获得性耐药限制了TMZ在临床的运用。掌握TMZ的分子药理机制和耐药产生的机理可以制定有效的治疗方案延缓TMZ耐药性的产生。
Glioma is a more common intracranial malignancy. Surgery, radiotherapy and chemotherapy with temozolomide (TMZ) have become the first-line treatment in Europe. TMZ alkylates DNA to exert anticancer effects by generating DNA adducts such as O6-methylguanine (N6-meG), N7-methylguanine (N7-meG) and N3-methyladenine . The anticancer effect of TMZ is mainly mediated by O6-meG. However, O6-meG-DNA methyltransferase (MGMT) can repair O6-meG in tumor cell DNA repair system, The role requires a complete base mismatch repair (MMR) system to participate. N7-meG is mainly repaired by the base excision repair (BER) system. TMZ in the clinical treatment of a very large individual differences, inherent or acquired resistance limits TMZ clinical use. To master molecular mechanism of TMZ and mechanism of drug resistance can develop effective treatment programs to delay the TMZ drug resistance.