Department of Pathology, University of Miyazaki, Kiyotake, Miyazaki 889-1692, Japan.
Anticancer Res. 2009 Nov;29(11):4845-54.
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.
尽管包括手术、化疗和放疗在内的多种治疗方法已经应用于胶质母细胞瘤患者，但他们的预后仍然极差。最近，烷化剂替莫唑胺（TMZ）已被证明可改善某些临床研究中包括胶质母细胞瘤在内的恶性胶质瘤患者的生存，并且已成为治疗新诊断和复发性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，MGMT 启动子未甲基化的肿瘤患者应如何治疗仍有待确定。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复发。在本文中，我们综述了 TMZ 对肿瘤细胞的作用机制和对 TMZ 的耐药性，并对胶质母细胞瘤患者的当前治疗和临床试验进行了概述。
