Targeted treatments for vascular malformations: current state of the art

Emmanuel Seront; Cedric Hermans; Laurence M Boon; Miikka Vikkula

doi:10.1016/j.jtha.2024.07.013

Targeted treatments for vascular malformations: current state of the art

J Thromb Haemost. 2024 Nov;22(11):2961-2975. doi: 10.1016/j.jtha.2024.07.013. Epub 2024 Aug 2.

Authors

Emmanuel Seront¹, Cedric Hermans², Laurence M Boon³, Miikka Vikkula⁴

Affiliations

¹ Center for Vascular Anomalies (a VASCERN VASCA European Reference Centre), Cliniques universitaires St Luc, University of Louvain, Brussels, Belgium. Electronic address: https://twitter.com/emmanuelseront.
² Center for Vascular Anomalies (a VASCERN VASCA European Reference Centre), Cliniques universitaires St Luc, University of Louvain, Brussels, Belgium; Institut Roi Albert II, Division of Hematology, Cliniques universitaires Saint-Luc, University of Louvain, Brussels, Belgium. Electronic address: https://twitter.com/HermansCedric.
³ Center for Vascular Anomalies (a VASCERN VASCA European Reference Centre), Cliniques universitaires St Luc, University of Louvain, Brussels, Belgium; Division of Plastic Surgery, Cliniques universitaires Saint-Luc, University of Louvain, Brussels, Belgium. Electronic address: https://twitter.com/LaurenceBoon4.
⁴ Center for Vascular Anomalies (a VASCERN VASCA European Reference Centre), Cliniques universitaires St Luc, University of Louvain, Brussels, Belgium; Deprtment of Human Molecular Genetics, de Duve Institute, University of Louvain, Brussels, Belgium; Walloon ExceLlence in Life Sciences and Biotechnology (WELBIO) and Walloon ExceLlence Research Institute (WEL Research Institute), Wavre, Belgium. Electronic address: [email protected].

PMID: 39097232
DOI: 10.1016/j.jtha.2024.07.013

Abstract

Vascular malformations, which arise from anomalies in angiogenesis, encompass capillary, lymphatic, venous, arteriovenous, and mixed malformations, each affecting specific vessel types. Historically, therapeutic options such as sclerotherapy and surgery have shown limited efficacy in complicated malformations. Most vascular malformations stem from hereditary or somatic mutations akin to oncogenic alterations, activating the PI3K-AKT-mTOR, RAS-MAPK-ERK, and G-protein coupled receptor pathways. Recognizing the parallels with oncogenic mutations, we emphasize the potential of targeted molecular inhibitors in the treatment of vascular malformations by repurposing anticancer drugs. This review delves into the recent development and future use of such agents for the management of slow- and fast-flow vascular malformations, including in more specific situations, such as prenatal treatment and the management of associated coagulopathies.

Keywords: angiogenesis inhibitor; anticoagulation; sirolimus; targeted therapy; thalidomide.

Publication types

Review

MeSH terms

Angiogenesis Inhibitors / therapeutic use
Animals
Antineoplastic Agents / therapeutic use
Drug Repositioning
Humans
Molecular Targeted Therapy*
Mutation
Neovascularization, Pathologic / drug therapy
Signal Transduction*
Vascular Malformations* / drug therapy
Vascular Malformations* / genetics
Vascular Malformations* / therapy

Substances

Angiogenesis Inhibitors
Antineoplastic Agents