Targeted Medical Therapies for Vascular Anomalies: A Clinical Review

Vascular anomalies represent a broad spectrum of disorders characterized by aberrant blood or lymphatic vessel development, which can lead to complex clinical phenotypes. Historically, vascular anomalies were classified solely on the basis of their clinical and histopathologic features. However, the last two decades have witnessed significant advances in our understanding of the genetic basis of these lesions. It is now recognized that many vascular anomalies arise from somatic pathogenic variants in key growth signaling pathways, including the PI3K-AKT-mTOR and RAS-MAPK pathways. These insights have catalyzed the development of targeted therapies designed to address the molecular underpinnings of disease. mTOR inhibitors, originally developed and widely used as anticancer agents, have also demonstrated significant efficacy in improving outcomes for patients with low-flow vascular malformations such as lymphatic malformations and venous malformations. Similarly, MEK inhibitors and other oncology drugs are being repurposed as promising therapeutic options for complex lymphatic anomalies and arteriovenous malformations, conditions that historically have had limited medical therapeutic options. Clinical trials for vascular anomalies are emerging, but questions remain about how to best measure response in these patients, as well as the optimal duration of treatment. This case-based review explores recent developments in precision medicine for vascular anomalies, highlighting a paradigm shift in the management of these complex and often therapeutically challenging disorders.