We focus on the recent development of in-vitro and in-vivo tools for the study of PIK3CA-mutant vascular malformations with special interest in preclinical models for drug testing.
Sensitive screening of recurrently mutated genes in vascular malformations may help to confirm the diagnosis and reveals potential therapeutic options with a significant contribution of PIK3CA/mTOR and RAS-MAPK pathway mutations.
Recent preclinical and clinical data demonstrated that sirolimus could offset the progression of vascular malformations and significantly improve quality of life of patients through inhibition of the Phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian Target of Rapamycin (mTOR) pathway.
Our findings reveal that PIK3CA mutations have a key role in the pathogenesis of VM and PIK3CA-driven experimental lesions can be effectively treated by PI3K/mTOR inhibitors.
Most individuals from Boston Children's Hospital who had isolated LM (16/17) or LM as part of a syndrome, such as KTS (19/21), fibro-adipose vascular anomaly (5/8), and congenital lipomatous overgrowth with vascular, epidermal, and skeletal anomalies syndrome (31/33) were somatic mosaic for PIK3CA mutations, with 5 specific PIK3CA mutations accounting for ∼ 80% of cases.