For instance, the mTOR inhibitor Sirolimus (Rapamycin), which inhibits the PI3K-Akt pathway downstream of PI3K, has been trialed in patients with slow-flow malformations, showing the greatest efficacy in lymphatic malformations with evidence for reduced lesion volume and improved management of comorbidities, such as pain, bleeding, and quality of life.11 This evidence concerns the gene PIK3CA and lymphatic malformation.