Flanigan Patrick M, Aghi Manish K
Cleveland Clinic Lerner College of Medicine, Cleveland, OH, USA.
Cell Mol Life Sci. 2015 Aug;72(16):3069-82. doi: 10.1007/s00018-015-1916-0. Epub 2015 May 6.
Because tumors require a vascular supply for their survival and growth, angiogenesis is considered an important therapeutic target in most human cancers including cancer of the central nervous system. Antiangiogenic therapy has focused on inhibitors of the vascular endothelial growth factor (VEGF) signaling pathway. VEGF pathway-targeted drugs have shown therapeutic efficacy in several CNS tumors and have been tried most frequently in glioblastoma. These therapies, however, have been less effective than anticipated as some patients do not respond to therapy and some receive only modest benefit. Underlying this suboptimal response are multiple mechanisms of drug resistance involving changes in both tumor cells and their microenvironment. In this review, we discuss the multiple proposed mechanisms by which neurological tumors evolve to become resistant to antiangiogenic therapies. A better understanding of these mechanisms, their context, and their interplay will likely facilitate improvements in pharmacological strategies for the targeted treatment of neurological tumors.
由于肿瘤的生存和生长需要血管供应，因此血管生成被认为是包括中枢神经系统癌症在内的大多数人类癌症的重要治疗靶点。抗血管生成疗法主要针对血管内皮生长因子（VEGF）信号通路的抑制剂。VEGF通路靶向药物在几种中枢神经系统肿瘤中已显示出治疗效果，并且在胶质母细胞瘤中应用最为频繁。然而，这些疗法的效果不如预期，因为一些患者对治疗无反应，而另一些患者仅获得适度的益处。这种次优反应的背后是多种耐药机制，涉及肿瘤细胞及其微环境的变化。在本综述中，我们讨论了神经肿瘤对抗血管生成疗法产生耐药性的多种潜在机制。更好地理解这些机制、它们的背景以及它们之间的相互作用，可能会促进神经肿瘤靶向治疗药理学策略的改进。
