Department of Neurology, Division of Neuro-Oncology, University of Virginia, Charlottesville, VA 22908-0432, USA.
Expert Rev Neurother. 2012 Jun;12(6):733-47. doi: 10.1586/ern.12.53.
High-grade gliomas, especially glioblastoma (GBM), are among the most aggressive and vascularized tumors. Angiogenesis plays a significant role in tumor growth and survival, and thus offers a target for anticancer treatment. Bevacizumab, a humanized monoclonal antibody against VEGF, was approved by the US FDA as a single agent for the treatment of recurrent glioblastoma. Significant radiographic response and progression-free survival were seen with bevacizumab treatment. However, benefits to overall survival remain undetermined. Other antiangiogenic strategies targeting VEGF, VEGF receptor (VEGFR) and other angiogenic factors have also been examined. Tumor progression after antiangiogenic treatment is inevitable, and effective salvage therapy is yet to be identified. Mechanisms of resistance to antiangiogenic therapy include activation of alternative proangiogenic pathways and increased tumor invasion. Strategies targeting these escape mechanisms are currently being investigated. The use of antiangiogenic drugs is generally well tolerated, although rare and potentially life-threatening adverse effects have been identified. With the striking antipermeability effect of anti-VEGF inhibitors, assessment of true tumor response has become a challenge. The Response Assessment in Neuro-Oncology Working Group has developed new criteria for clinical trials in patients with high-grade glioma. Identification of neuroimaging advances and biologic markers will greatly enhance treatment strategies for these patients.
高级别胶质瘤，尤其是胶质母细胞瘤（GBM），是最具侵袭性和血管生成的肿瘤之一。血管生成在肿瘤生长和存活中起着重要作用，因此成为抗癌治疗的靶点。贝伐单抗，一种针对 VEGF 的人源化单克隆抗体，被美国 FDA 批准为复发性 GBM 的单一药物治疗方法。贝伐单抗治疗可观察到显著的影像学反应和无进展生存期。然而，对总生存期的益处仍不确定。其他针对 VEGF、VEGF 受体（VEGFR）和其他血管生成因子的抗血管生成策略也已被研究。抗血管生成治疗后的肿瘤进展是不可避免的，尚未确定有效的挽救治疗方法。对抗血管生成治疗的耐药机制包括激活替代的促血管生成途径和增加肿瘤侵袭。目前正在研究针对这些逃逸机制的策略。抗血管生成药物的使用通常耐受性良好，尽管已经确定了一些罕见且可能危及生命的不良反应。由于抗 VEGF 抑制剂具有显著的抗通透性作用，评估真正的肿瘤反应已成为一项挑战。神经肿瘤学工作组制定了高级别胶质瘤患者临床试验的新标准。识别神经影像学进展和生物标志物将极大地增强这些患者的治疗策略。
