Mosteiro Alejandra, Pedrosa Leire, Ferrés Abel, Diao Diouldé, Sierra Àngels, González José Juan
Department of Neurosurgery, Hospital Clínic de Barcelona, 08036 Barcelona, Spain.
Laboratory of Experimental Oncological Neurosurgery, Hospital Clínic de Barcelona, 08036 Barcelona, Spain.
Biomedicines. 2022 May 31;10(6):1285. doi: 10.3390/biomedicines10061285.
Glioblastoma multiforme, the deadliest primary brain tumor, is characterized by an excessive and aberrant neovascularization. The initial expectations raised by anti-angiogenic drugs were soon tempered due to their limited efficacy in improving the overall survival. Intrinsic resistance and escape mechanisms against anti-VEGF therapies evidenced that tumor angiogenesis is an intricate multifaceted phenomenon and that vessels not only support the tumor but exert indispensable interactions for resistance and spreading. This holistic review covers the essentials of the vascular microenvironment of glioblastoma, including the perivascular niche components, the vascular generation patterns and the implicated signaling pathways, the endothelial-tumor interrelation, and the interconnection between vessel aberrancies and immune disarrangement. The revised concepts provide novel insights into the preclinical models and the potential explanations for the failure of conventional anti-angiogenic therapies, leading to an era of new and combined anti-angiogenic-based approaches.
多形性胶质母细胞瘤是最致命的原发性脑肿瘤，其特征是过度且异常的新生血管形成。抗血管生成药物最初带来的期望很快因它们在改善总生存期方面的有限疗效而有所缓和。针对抗VEGF疗法的内在抗性和逃逸机制表明，肿瘤血管生成是一个复杂的多方面现象，而且血管不仅支持肿瘤，还在抗性和扩散方面发挥不可或缺的相互作用。这篇全面的综述涵盖了胶质母细胞瘤血管微环境的要点，包括血管周围生态位成分、血管生成模式及相关信号通路、内皮细胞与肿瘤的相互关系，以及血管异常与免疫紊乱之间的相互联系。这些修订后的概念为临床前模型提供了新的见解，并对传统抗血管生成疗法的失败给出了潜在解释，从而开启了基于新型联合抗血管生成方法的时代。
