Numerous antiangiogenic agents with diverse mechanisms of action are currently under investigation for the treatment of patients with glioblastoma (GBM), a diagnosis that continues to carry a poor prognosis despite maximal conventional therapy. Early clinical trials suggest that antiangiogenic drugs, which target the blood vessels of these highly angiogenic tumors, may have clinical benefit in GBM patients. Antiangiogenic agents have potent antiedema and steroid-sparing effects in patients, and emerging data suggest that these drugs may modestly improve progression-free survival. Although these early results are encouraging, several issues arise regarding the use and efficacy of these agents. Interpretation of the radiographic changes that occur after treatment with antiangiogenic agents presents a major challenge. Still lacking are reliable radiographic and biologic markers that can predict which patients will benefit from treatment and that accurately indicate response and progression during therapy. In addition, most patients treated with antiangiogenic drugs eventually progress, and the mechanisms by which tumors escape from therapy are only beginning to be understood. Larger prospective trials that incorporate correlative biomarker studies will be required to address these challenges. Here, we summarize the clinical experience with antiangiogenic therapy in patients with malignant gliomas (MG), review the major issues concerning the use and development of these agents, and discuss strategies that may build upon the initial gains observed with antiangiogenic agents.

中文翻译：

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治疗恶性神经胶质瘤的抗血管生成策略。


目前正在研究多种具有不同作用机制的抗血管生成药物来治疗胶质母细胞瘤（GBM）患者，尽管进行了最大程度的常规治疗，但这种诊断仍导致预后不良。早期临床试验表明，针对这些高度血管生成肿瘤的血管的抗血管生成药物可能对 GBM 患者具有临床益处。抗血管生成药物对患者具有有效的抗水肿和节省类固醇的作用，新出现的数据表明这些药物可能会适度改善无进展生存期。尽管这些早期结果令人鼓舞，但在这些药物的使用和功效方面出现了一些问题。解释抗血管生成药物治疗后发生的放射线变化是一个重大挑战。仍然缺乏可靠的放射学和生物标志物，可以预测哪些患者将从治疗中受益，并准确指示治疗期间的反应和进展。此外，大多数接受抗血管生成药物治疗的患者最终都会出现进展，而肿瘤逃避治疗的机制才刚刚开始被了解。需要进行更大规模的前瞻性试验，纳入相关的生物标志物研究来应对这些挑战。在这里，我们总结了恶性神经胶质瘤（MG）患者抗血管生成治疗的临床经验，回顾了有关这些药物的使用和开发的主要问题，并讨论了可能建立在抗血管生成药物所观察到的初步收益基础上的策略。