Anti-glioma therapy with temozolomide and status of the DNA-repair gene MGMT.
Anti-glioma therapy with temozolomide and status of the DNA-repair gene MGMT.
复制标题
DOI：
--
复制
发表时间：
2009-11
影响因子：
2
通讯作者：
T. Fukushima;H. Takeshima;H. Kataoka
中科院分区：
文献类型：
--
作者：
T. Fukushima;H. Takeshima;H. Kataoka
胶质母细胞瘤患者的预后非常差，尽管多模式治疗包括手术，化疗和放疗。近年来，在一些临床研究中，烷基化剂替莫唑胺（TMZ）已被证明可以提高恶性胶质瘤（包括胶质母细胞瘤）患者的生存率，并已成为治疗新诊断和复发恶性胶质瘤的标准方法之一。DNA修复酶O(6)-甲基鸟嘌呤-DNA甲基转移酶（MGMT）的表观遗传沉默是TMZ治疗患者预后良好的最强预测标志物。然而，如何治疗缺乏MGMT启动子甲基化的肿瘤患者仍有待确定。此外，即使是对tmz敏感的胶质母细胞瘤患者也无法避免最终的复发。本文就TMZ对肿瘤细胞的作用机制及对TMZ的耐药性进行综述，并对目前胶质母细胞瘤患者的治疗和临床试验进行综述。
The prognosis of patients with glioblastoma is extremely poor despite multimodal treatments including surgery, chemotherapy and radiotherapy. Recently, the alkylating agent, temozolomide (TMZ) has been shown to improve survival in patients with malignant gliomas, including those with glioblastoma in some clinical studies, and has become one of the standard modalities for treatment of newly diagnosed and recurrent malignant gliomas. The epigenetic silencing of the DNA repair enzyme O(6)-methylguanine-DNA-methyltransferase (MGMT) is the strongest predictive marker for favorable outcome in patients treated with TMZ. However, it remains to be determined how patients with tumors lacking MGMT promoter methylation should be treated. Moreover, even patients with TMZ-sensitive glioblastoma cannot avoid eventual recurrence. In this article, we review the mechanism of the effect of TMZ on tumor cells and resistance to TMZ, and provide an overview of the current management and trials for patients with glioblastoma.