Sirolimus for vascular anomalies

Abstract

Vascular anomalies (hemangiomas and malformations) are characterized by abnormal blood or lymphatic vessels in the skin or soft ­tissues. In pediatric hematology/oncology, we encounter challenging cases, such as the Kasabach–Merritt phenomenon, lymphatic diseases, venous malformations, and Klippel–Trenaunay syndrome. Treatment varies depending on the lesion size and symptoms, ranging from observation to surgical resection or sclerotherapy. A standard therapy for intractable cases with large, unresectable lesions remains unavailable. Recent studies have identified genetic abnormalities in the PI3K/AKT/mTOR and RAS/MAPK/MEK pathways as key ­contributors to these conditions, and advancements have been made in novel therapies. In January 2024, sirolimus, an mTOR inhibitor, was approved for use in Japan. It has shown efficacy in reducing lesion size and alleviating symptoms, such as bleeding and pain; ­however, uncertainties remain regarding its mechanisms, usage, and indications. This review outlines the refractory vascular anomalies and discusses the therapeutic applications of sirolimus.