Tamura Ryota, Tanaka Toshihide, Miyake Keisuke, Yoshida Kazunari, Sasaki Hikaru
Department of Neurosurgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
Department of Neurosurgery, Jikei University Kashiwa Hospital, 163-1 Kashiwashita, Kashiwa-shi, Chiba, 277-8567, Japan.
Brain Tumor Pathol. 2017 Apr;34(2):62-77. doi: 10.1007/s10014-017-0284-x. Epub 2017 Apr 6.
Vascular endothelial growth factor (VEGF) is an attractive target of antiangiogenic therapy in glioblastomas. Bevacizumab (Bev), a humanized anti-VEGF antibody, is associated with the improvement of progression-free survival and performance status in patients with glioblastoma. However, randomized trials uniformly suggest that these favorable clinical effects of Bev do not translate into an overall survival benefit. The mechanisms of action of Bev appear to include the inhibition of tumor angiogenesis, as well as indirect effects such as the depletion of niches for glioma stem cells and stimulation of antitumor immunity. Although several molecules/pathways have been reported to mediate adaptation and resistance to Bev, including the activation of alternative pro-angiogenic pathways, the resistance mechanisms have not been fully elucidated; for example, the mechanism that reinduces tumor hypoxia remains unclarified. The identification of imaging characteristics or biomarkers predicting the response to Bev, as well as the better understanding of the mechanisms of action and resistance, is crucial to improve the overall clinical outcome and optimize individual therapy. In this article, the authors review the results of important clinical trials/studies, the current understanding of the mechanisms of action and resistance, and the knowledge of imaging characteristics and biomarkers predicting the response to Bev.
血管内皮生长因子（VEGF）是胶质母细胞瘤抗血管生成治疗中一个有吸引力的靶点。贝伐单抗（Bev），一种人源化抗VEGF抗体，与胶质母细胞瘤患者无进展生存期和功能状态的改善相关。然而，随机试验一致表明，Bev的这些有利临床效果并未转化为总生存期获益。Bev的作用机制似乎包括抑制肿瘤血管生成，以及诸如减少胶质瘤干细胞龛位和刺激抗肿瘤免疫等间接作用。尽管已报道有几种分子/途径介导对Bev的适应和耐药，包括激活替代性促血管生成途径，但耐药机制尚未完全阐明；例如，重新诱导肿瘤缺氧的机制仍不清楚。识别预测对Bev反应的影像学特征或生物标志物，以及更好地理解作用机制和耐药性，对于改善总体临床结局和优化个体化治疗至关重要。在本文中，作者回顾了重要临床试验/研究的结果、对作用机制和耐药性的当前认识，以及预测对Bev反应的影像学特征和生物标志物的相关知识。
