Nguyen Ha-Long, Boon Laurence M, Vikkula Miikka
Laboratory of Human Molecular Genetics, de Duve Institute, University of Louvain (UCL), Brussels, Belgium.
Center for Vascular Anomalies, Cliniques Universitaires Saint-Luc, University of Louvain (UCL), Brussels, Belgium.
Semin Intervent Radiol. 2017 Sep;34(3):233-238. doi: 10.1055/s-0037-1604296. Epub 2017 Sep 11.
Vascular anomalies arise as a consequence of improper development and maintenance of the vasculature. Our knowledge on the pathophysiological bases of vascular anomalies has skyrocketed during the past 5 years. It is becoming clear that common intracellular signaling pathways are often activated by mutations, causing endothelial cell dysfunction. These mutations cause hyperactivation of two major intracellular signaling pathways that may be controlled by inhibitors developed for cancer treatment. Although we do not know yet all the downstream effects, it has become evident that normalization of the abnormal signaling is an interesting target for therapy. This is a major paradigm change, as developmental malformations were considered to be inert to any molecular treatment.
血管异常是由于血管系统发育和维持不当而产生的。在过去5年里，我们对血管异常病理生理基础的认识有了飞速增长。越来越清楚的是，常见的细胞内信号通路常常因突变而被激活，导致内皮细胞功能障碍。这些突变导致两条主要细胞内信号通路过度激活，而这两条通路可能由为癌症治疗开发的抑制剂所控制。尽管我们尚未知晓所有的下游效应，但异常信号的正常化已成为一个有趣的治疗靶点，这一点已很明显。这是一个重大的范式转变，因为发育畸形曾被认为对任何分子治疗都无反应。
