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.