Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO, USA; Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA; Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO, USA.
IGM Biosciences, Mountain View, CA, USA.
Cell. 2019 Mar 7;176(6):1248-1264. doi: 10.1016/j.cell.2019.01.021.
The discovery of vascular endothelial-derived growth factor (VEGF) has revolutionized our understanding of vasculogenesis and angiogenesis during development and physiological homeostasis. Over a short span of two decades, our understanding of the molecular mechanisms by which VEGF coordinates neurovascular homeostasis has become more sophisticated. The central role of VEGF in the pathogenesis of diverse cancers and blinding eye diseases has also become evident. Elucidation of the molecular regulation of VEGF and the transformative development of multiple therapeutic pathways targeting VEGF directly or indirectly is a powerful case study of how fundamental research can guide innovation and translation. It is also an elegant example of how agnostic discovery and can transform our understanding of human disease. This review will highlight critical nodal points in VEGF biology, including recent developments in immunotherapy for cancer and multitarget approaches in neovascular eye disease.
血管内皮衍生生长因子(VEGF)的发现彻底改变了我们对发育和生理稳态过程中血管发生和血管生成的理解。在短短二十年的时间里,我们对 VEGF 协调神经血管稳态的分子机制的理解变得更加复杂。VEGF 在多种癌症和致盲眼病发病机制中的核心作用也变得明显。阐明 VEGF 的分子调控以及直接或间接靶向 VEGF 的多种治疗途径的变革性发展是基础研究如何指导创新和转化的一个有力案例。它也是一个很好的例子,说明了无偏见的发现如何改变我们对人类疾病的认识。本综述将重点介绍 VEGF 生物学中的关键节点,包括癌症免疫治疗的最新进展和新生血管性眼病的多靶点方法。