Introduction: Vascular malformations occur during early vascular development
resulting in abnormally formed vessels that can manifest as arterial,
venous, capillary or lymphatic lesions or in combination, and include
local tissue overdevelopment. Vascular malformations are largely caused
by sporadic somatic gene mutations. This article aims to review and
discuss current molecular signaling pathways and therapeutic targets for
vascular malformations and to classify vascular malformations according
to the molecular pathways involved. /
Methods: A literature review was performed using Embase and Medline. Different
MeSH terms were combined for the search strategy, with the aim of
encompassing all studies describing the classification, pathogenesis and
treatment of vascular malformations. /
Results: Major pathways involved in the pathogenesis of vascular malformations
are VEGF, Ras/Raf/MEK/ERK, Angiopoietin-TIE2, TGF- β and
PI3K/AKT/mTOR. These pathways are involved in controlling cellular
growth, apoptosis, differentiation and proliferation, and play a central
role in endothelial cell signaling and angiogenesis. Many vascular
malformations share similar aberrant molecular signaling pathways with
cancers and inflammatory disorders. Therefore, selective anti-cancer
agents and immunosuppressants may be beneficial in treating vascular
malformations of specific mutations. The current classification systems of
vascular malformations including the ISSVA classification are primarily
observational and clinical, and are not based on the molecular pathways
involved in the pathogenesis of the condition. /
Conclusions: Several molecular pathways with potential therapeutic targets have been
demonstrated to contribute to the development of various vascular
anomalies. Classifying vascular malformations based on their molecular
pathogenesis may improve treatment by determining the underlying
nature of the condition and their potential therapeutic target
