胶质母细胞瘤抗血管生成治疗的新方向
New Directions in Anti-Angiogenic Therapy for Glioblastoma.
作者信息
Wang Nancy, Jain Rakesh K, Batchelor Tracy T
机构信息
Stephen E. and Catherine Pappas Center for Neuro-Oncology, Massachusetts General Hospital, Boston, MA, USA.
Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, USA.
出版信息
Neurotherapeutics. 2017 Apr;14(2):321-332. doi: 10.1007/s13311-016-0510-y.
Abstract
Anti-angiogenic therapy has become an important component in the treatment of many solid tumors given the importance of adequate blood supply for tumor growth and metastasis. Despite promising preclinical data and early clinical trials, anti-angiogenic agents have failed to show a survival benefit in randomized controlled trials of patients with glioblastoma. In particular, agents targeting vascular endothelial growth factor (VEGF) appear to prolong progression free survival, possibly improve quality of life, and decrease steroid usage, yet the trials to date have demonstrated no extension of overall survival. In order to improve duration of response and convey a survival benefit, additional research is still needed to explore alternative pro-angiogenic pathways, mechanisms of resistance, combination strategies, and biomarkers to predict therapeutic response.
摘要
鉴于充足的血液供应对肿瘤生长和转移的重要性，抗血管生成疗法已成为许多实体瘤治疗的重要组成部分。尽管临床前数据和早期临床试验前景乐观，但抗血管生成药物在胶质母细胞瘤患者的随机对照试验中未能显示出生存获益。特别是，靶向血管内皮生长因子（VEGF）的药物似乎可延长无进展生存期，可能改善生活质量，并减少类固醇的使用，但迄今为止的试验表明总体生存期并未延长。为了提高缓解持续时间并带来生存获益，仍需要进一步研究以探索替代的促血管生成途径、耐药机制、联合策略以及预测治疗反应的生物标志物。
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2
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3
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9
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