For example, mammalian target of rapamycin (mTOR) signaling is initiated in the phosphoinositide 3-kinase (PI3K)/AKT pathway involved in cell cycle regulation and often implicated in patients with vascular anomalies and overgrowth who have somatic mutations in PIK3CA. This finding has led to targeting of the overactive PI3K/AKT/mTOR pathway with sirolimus (an mTOR inhibitor), which has demonstrated clinical benefit in several vascular malformations and tumors (10, 11). This evidence concerns the gene AKT1 and vascular malformation.