PIK3CA encodes the 110-kD catalytic α-subunit of PI(3)K (p110α), which converts phosphatidylinositol (3,4)-bisphosphate (PtdIns(3,4)P 2) to phosphatidylinositol (3,4,5)-triphosphate (PtdIns(3,4,5)P 3). Class I PI(3)K contains four catalytic isoforms (p110α, p110β, p110δ and p110γ), which carry out non-redundant signalling functions 1. The phosphoinositide-3 kinases (PI(3)Ks) are key lipid kinases that control signalling pathways involved in cell proliferation, motility, survival and metabolism 1. In conclusion, this study provides the first direct evidence supporting PIK3CA inhibition as a promising therapeutic strategy in patients with PROS. The treatment was not associated with any substantial side effects. Previously intractable vascular tumours became smaller, congestive heart failure was improved, hemihypertrophy was reduced, and scoliosis was attenuated. The drug improved the disease symptoms in all patients. On the basis of these results, we used BYL719 to treat nineteen patients with PROS. Here, we describe a postnatal mouse model of PROS/CLOVES that partially recapitulates the human disease, and demonstrate the efficacy of BYL719, an inhibitor of PIK3CA, in preventing and improving organ dysfunction. This rare condition has no specific treatment and a poor survival rate. CLOVES syndrome (congenital lipomatous overgrowth, vascular malformations, epidermal naevi, scoliosis/skeletal and spinal syndrome) is a genetic disorder that results from somatic, mosaic gain–of–function mutations of the PIK3CA gene, and belongs to the spectrum of PIK3CA-related overgrowth syndromes (PROS).
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