Current and emerging pharmacotherapies for treating vascular malformations

INTRODUCTION: Vascular malformations are chronic, often progressive disorders for which conventional procedures frequently provide incomplete control. Advances in molecular genetics have revealed recurrent pathway alterations that now enable mechanism-based pharmacologic treatment. AREAS COVERED: This narrative review summarizes current and emerging targeted therapies for vascular malformations, including mTOR, PI3K, MEK, anti-angiogenic, and genotype-specific inhibitors. Vascular malformations - capillary, lymphatic, venous, and arteriovenous - are increasingly recognized as disorders driven by dysregulation of the PI3K - AKT - mTOR and RAS - MAPK - ERK pathways, supporting rational repurposing of targeted anticancer drugs. We discuss clinical evidence, limitations, and practical considerations for sirolimus, PI3K inhibitors, thalidomide, MEK inhibitors, and KRAS-directed agents, as well as emerging combination and intermittent strategies to balance efficacy and toxicity. The review is based on a structured PubMed/MEDLINE search up to December 2025, prioritizing original translational studies, prospective trials, and large clinical series. EXPERT OPINION: Targeted therapies are shifting management from procedure-centered to biology-guided care. Future progress depends on standardized molecular testing, patient-centered outcomes, and optimized treatment duration to achieve durable disease control with acceptable long-term toxicity.