Weathers Shiao-Pei, de Groot John
Oncology (Williston Park). 2015 Oct;29(10):720-7.
Glioblastoma is the most common malignant primary brain tumor that is universally lethal, despite optimized treatment including surgery, radiation, and chemotherapy. Targeting angiogenesis has been and continues to be an attractive therapeutic modality in both newly diagnosed and recurrent glioblastoma patients. Vascular endothelial growth factor (VEGF) is the most abundant and important mediator of angiogenesis in glioblastoma. Multiple strategies have been developed to target VEGF/VEGF receptor (VEGFR)-mediated angiogenesis, including VEGF blockade, VEGF Trap, and suppression of VEGFR signaling via receptor tyrosine kinase inhibitors (TKIs). These strategies have been explored in a spectrum of clinical trials, yielding findings that have all contributed to furthering our overall understanding of antiangiogenic therapy. The role of these agents and how to best incorporate them into the treatment paradigm for glioblastoma continues to evolve as understanding of resistance mechanisms improves. Although the excitement surrounding antiangiogenic therapy has waned over the years due to the lack of durable responses and survival benefit, there continues to be hope that combining antiangiogenic therapies with radiation therapy, cytotoxic drugs, immunotherapy, and targeted molecular agents may greatly enhance treatment strategies for high-grade gliomas.
胶质母细胞瘤是最常见的原发性恶性脑肿瘤，尽管采用了包括手术、放疗和化疗在内的优化治疗，但其致死率仍很高。在新诊断和复发性胶质母细胞瘤患者中，靶向血管生成一直是且仍然是一种有吸引力的治疗方式。血管内皮生长因子（VEGF）是胶质母细胞瘤中血管生成最丰富且最重要的介质。已经开发了多种针对VEGF/VEGF受体（VEGFR）介导的血管生成的策略，包括VEGF阻断、VEGF Trap以及通过受体酪氨酸激酶抑制剂（TKIs）抑制VEGFR信号传导。这些策略已在一系列临床试验中进行了探索，所得到的结果都有助于增进我们对抗血管生成治疗的整体理解。随着对耐药机制的认识不断提高，这些药物的作用以及如何将它们最佳地纳入胶质母细胞瘤的治疗模式仍在不断演变。尽管由于缺乏持久反应和生存获益，多年来围绕抗血管生成治疗的热情有所消退，但人们仍然希望将抗血管生成疗法与放射治疗、细胞毒性药物、免疫疗法和靶向分子药物相结合，可能会大大增强高级别胶质瘤的治疗策略。
