Zhang Meng, Ye Gengfan, Li Jianyi, Wang Yunyan
Department of Neurosurgery, Qilu Hospital of Shandong University, Brain Science Research Institute of Shandong University, Jinan, 250012, People's Republic of China.
Department of Pathology and Laboratory Medicine, North Shore-Long Island Jewish Health System, Lake Success, NY, USA.
Brain Tumor Pathol. 2015 Oct;32(4):229-36. doi: 10.1007/s10014-015-0233-5. Epub 2015 Oct 5.
Glioblastoma (GBM) is the most highly malignant brain tumor in the human central nerve system. In this paper, we review new and significant molecular findings on angiogenesis and possible resistance mechanisms. Expression of a number of genes and regulators has been shown to be upregulated in GBM microvessel cells, such as interleukin-8, signal transducer and activator of transcription 3, Tax-interacting protein-1, hypoxia induced factor-1 and anterior gradient protein 2. The regulator factors that may strongly promote angiogenesis by promoting endothelial cell metastasis, changing the microenvironment, enhancing the ability of resistance to anti-angiogenic therapy, and that inhibit angiogenesis are reviewed. Based on the current knowledge, several potential targets and strategies are proposed for better therapeutic outcomes, such as its mRNA interference of DII4-Notch signaling pathway and depletion of b1 integrin expression. We also discuss possible mechanisms underlying the resistance to anti-angiogenesis and future directions and challenges in developing new targeted therapy for GBM.
胶质母细胞瘤（GBM）是人类中枢神经系统中恶性程度最高的脑肿瘤。在本文中，我们综述了关于血管生成和可能的耐药机制的新的重要分子研究结果。已证明许多基因和调节因子在GBM微血管细胞中表达上调，如白细胞介素-8、信号转导和转录激活因子3、Tax相互作用蛋白-1、缺氧诱导因子-1和前梯度蛋白2。本文综述了可能通过促进内皮细胞转移、改变微环境、增强抗血管生成治疗抵抗能力来强烈促进血管生成以及抑制血管生成的调节因子。基于目前的知识，提出了几个潜在的靶点和策略以获得更好的治疗效果，如对DII4-Notch信号通路进行mRNA干扰以及降低β1整合素的表达。我们还讨论了抗血管生成耐药的可能机制以及GBM新靶向治疗开发的未来方向和挑战。
