Vascular malformations are rare diseases that consist in an overgrowth of the blood and lymphatic vessels. These are congenital diseases that are present when the patient is born, thus they occur during embryonic development. Vascular malformations grow with the patient and they are very painful and disfiguring, they cause bleedings, infections and can invade and obstruct vital organs. Recently, we discovered new causing mutations leading to venous malformations, the most common type of vascular malformations. These mutations are similar to those found in epithelial tumours such as breast and colon; however, the specific biology and impact of these mutations in vascular malformations were unknown. Also, the therapeutic effect of targeted therapies that can be repurposed from oncology was underexplored due to the lack of biological insights and preclinical tools for these diseases. With this project we aimed to i) understand the biological mechanisms that lead to the pathogenesis of these diseases, ii) generate state of the art preclinical tools, and iii) assess a spectrum of targeted therapies for these rare diseases. Findings and studies from this project have impacted the way patients with vascular malformations are managed since we have translated our results into the clinic through our clinical partners and this has had an impact on their genetic and molecular diagnosis. Also, our preclinical tools have allowed pharma companies to test molecular inhibitors specifically for these rare diseases, helping in the process towards clinical trials.
