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A Patient-Derived Xenograft Model for Venous Malformation

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Theranostic Advances in Vascular Malformations.

Valérie Dekeuleneer¹, Emmanuel Seront², An Van Damme³

¹Centre for Vascular Anomalies, Division of Plastic Surgery, Cliniques universitaires Saint-Luc; European Reference Network for Rare Multisystemic Vascular Diseases Vascular Anomalies European Reference Centre, Brussels, Belgium.

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Summary

Vascular malformations stem from gene mutations affecting key signaling pathways. Targeted therapies, repurposed from cancer drugs, now offer new treatment options for these anomalies.

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Area of Science:

Vascular biology and genetics
Molecular medicine
Oncology drug repurposing

Background:

Vascular malformations are classified based on affected vessel types (capillary, lymphatic, venous, arteriovenous, mixed).
Traditional treatments like sclerotherapy and surgery had limited efficacy.
Recent research identified genetic mutations as the primary cause of most vascular malformations.

Purpose of the Study:

To explore the molecular basis of vascular malformations.
To investigate the role of specific signaling pathways in disease pathogenesis.
To evaluate targeted molecular inhibitors as novel therapeutic strategies.

Main Methods:

Analysis of genetic mutations underlying vascular malformations.
Investigation of RAS/MAPK and PI3K/AKT/mTOR pathway hyperactivity.
Testing of repurposed anticancer drugs as targeted molecular inhibitors.

Main Results:

Identified inherited and somatic mutations in genes causing vascular malformations.
Confirmed hyperactivity in the RAS/mitogen-activated protein kinase (MAPK) pathway.
Confirmed hyperactivity in the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway.
Demonstrated the potential of targeted molecular inhibitors.

Conclusions:

Vascular malformations are driven by specific genetic mutations affecting key cellular signaling.
Targeted molecular therapies, particularly repurposed anticancer drugs, represent a promising new treatment avenue for vascular anomalies.