Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, College of Medicine, University of Illinois at Chicago, Chicago, IL.
Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL.
Med Res Rev. 2018 Sep;38(6):1769-1798. doi: 10.1002/med.21496. Epub 2018 Mar 12.
In recent years, lymphangiogenesis, the process of lymphatic vessel formation from existing lymph vessels, has been demonstrated to have a significant role in diverse pathologies, including cancer metastasis, organ graft rejection, and lymphedema. Our understanding of the mechanisms of lymphangiogenesis has advanced on the heels of studies demonstrating vascular endothelial growth factor C as a central pro-lymphangiogenic regulator and others identifying multiple lymphatic endothelial biomarkers. Despite these breakthroughs and a growing appreciation of the signaling events that govern the lymphangiogenic process, there are no FDA-approved drugs that target lymphangiogenesis. In this review, we reflect on the lessons available from the development of antiangiogenic therapies (26 FDA-approved drugs to date), review current lymphangiogenesis research including nanotechnology in therapeutic drug delivery and imaging, and discuss molecules in the lymphangiogenic pathway that are promising therapeutic targets.
近年来,淋巴管生成(即从现有淋巴管形成新淋巴管的过程)已被证明在多种病理中发挥重要作用,包括癌症转移、器官移植排斥和淋巴水肿。随着研究表明血管内皮生长因子 C 是主要的促淋巴管生成调节剂,以及其他研究确定了多种淋巴管内皮生物标志物,我们对淋巴管生成机制的理解也取得了进展。尽管取得了这些突破,并且越来越认识到调控淋巴管生成过程的信号事件,但目前还没有获得 FDA 批准的针对淋巴管生成的药物。在这篇综述中,我们反思了抗血管生成疗法(迄今为止已有 26 种 FDA 批准的药物)开发中获得的经验教训,回顾了当前的淋巴管生成研究,包括治疗性药物递送和成像中的纳米技术,并讨论了淋巴管生成途径中有希望成为治疗靶点的分子。