Miletic Hrvoje, Niclou Simone P, Johansson Mikael, Bjerkvig Rolf
Department of Biomedicine, University of Bergen, NorLux Neuro-Oncology, Bergen, Norway.
Expert Opin Ther Targets. 2009 Apr;13(4):455-68. doi: 10.1517/14728220902806444.
Glioblastoma multiforme (GBM) has a very poor prognosis and novel treatment strategies are urgently needed. GBM appears to be an optimal target for anti-angiogenic therapy as the tumour shows a high degree of endothelial cell proliferation and pro-angiogenic growth factor expression.
To examine the role of angiogenic factors (particularly VEGF) in glioma and whether inhibition of these factors can be used as a treatment.
A review of relevant literature.
RESULTS/CONCLUSIONS: Anti-angiogenic therapy has fulfilled the proof of concept in glioma animal models. In glioma patients, the efficacy of anti-angiogenic mono-therapies initially has been disappointing. However recent clinical trials combining bevacizumab, an anti-VEGF antibody, with chemotherapy reported very encouraging response rates. Although randomized phase III clinical trials with anti-angiogenic molecules are not yet available for GBM patients, this treatment regimen is already applied off protocol in several clinical centers. It should be kept in mind though that tumours can develop escape mechanisms. In particular invasive cells, which migrate away from the highly vascularized tumour core, are not targeted by anti-angiogenic therapies. In our opinion, the future of anti-angiogenic therapy will rely on a combination strategy including chemotherapy and drugs that target invasive glioma cells.
多形性胶质母细胞瘤（GBM）预后极差，急需新的治疗策略。GBM似乎是抗血管生成治疗的理想靶点，因为该肿瘤显示出高度的内皮细胞增殖和促血管生成生长因子表达。
研究血管生成因子（尤其是血管内皮生长因子）在胶质瘤中的作用，以及抑制这些因子是否可用于治疗。
对相关文献进行综述。
结果/结论：抗血管生成治疗在胶质瘤动物模型中已完成概念验证。在胶质瘤患者中，抗血管生成单一疗法的疗效起初令人失望。然而，最近将抗血管内皮生长因子抗体贝伐单抗与化疗联合应用的临床试验报告了非常令人鼓舞的缓解率。虽然针对GBM患者的抗血管生成分子的随机III期临床试验尚未开展，但这种治疗方案已在多个临床中心超方案应用。不过应该记住，肿瘤可能会产生逃逸机制。特别是侵袭性细胞，它们从高度血管化的肿瘤核心迁移出来，不会被抗血管生成治疗所靶向。我们认为，抗血管生成治疗的未来将依赖于包括化疗和靶向侵袭性胶质瘤细胞的药物的联合策略。
