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[胶质母细胞瘤中的抗血管生成策略]

[Anti-angiogenic strategies in glioblastoma].

作者信息

Guillamo J-S

机构信息

Service de neurologie, hôpital Côte-de-Nacre, CHU de Caen, 14033 Caen cedex, France.

出版信息

Rev Neurol (Paris). 2011 Oct;167(10):662-7. doi: 10.1016/j.neurol.2011.07.008. Epub 2011 Sep 1.

Abstract

INTRODUCTION

Glioblastoma, a highly angiogenic tumor, has poor prognosis despite aggressive conventional therapies combining surgery, chemotherapy and radiotherapy. Anti-angiogenic strategies that have recently come to the clinic, are the most promising therapeutic approaches for these tumors.

STATE OF ART

Tumor hypoxia is the main trigger of angiogenesis processes driven primarily by vascular endothelial growth factor (VEGF). Clinical data indicate that inhibitors of VEGF such as bevacizumab or VEGF receptors such as tyrosine kinase inhibitors are of potential interest in the treatment of recurrent glioblastoma, with an acceptable toxicity. However, despite high rate of initial radiological response and rapid clinical improvement in about half of patients, therapeutic failure is the rule. Mechanisms of resistance remain poorly understood but an invasive phenotype and alternative angiogenesis factors may contribute to tumor escape.

CONCLUSIONS AND PERSPECTIVES

Anti-angiogenic strategies already play an important role in the management of recurrent glioblastoma. However, optimal combination and schedules of angiogenic inhibitors with radiotherapy and chemotherapy remain to be established. Important randomized clinical trials currently investigate therapeutic combinations for newly diagnosed glioblastoma.

摘要

引言

胶质母细胞瘤是一种具有高度血管生成性的肿瘤,尽管采用了手术、化疗和放疗相结合的积极传统疗法,但其预后仍然很差。最近进入临床的抗血管生成策略是治疗这些肿瘤最有前景的治疗方法。

现状

肿瘤缺氧是主要由血管内皮生长因子(VEGF)驱动的血管生成过程的主要触发因素。临床数据表明,VEGF抑制剂(如贝伐单抗)或VEGF受体抑制剂(如酪氨酸激酶抑制剂)在复发性胶质母细胞瘤的治疗中具有潜在价值,且毒性可接受。然而,尽管约一半患者最初的放射学反应率较高且临床迅速改善,但治疗失败却是常见情况。耐药机制仍知之甚少,但侵袭性表型和替代性血管生成因子可能导致肿瘤逃逸。

结论与展望

抗血管生成策略已在复发性胶质母细胞瘤的治疗中发挥重要作用。然而,血管生成抑制剂与放疗和化疗的最佳联合方案和给药时间表仍有待确定。目前重要的随机临床试验正在研究新诊断胶质母细胞瘤的治疗组合。

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