Targeted treatments for brain arteriovenous malformations: a review

Brain arteriovenous malformations (bAVMs) are abnormal tangles of vessels that shunt pressurized arterial blood into low-pressure veins, creating a fragile structure prone to rupture, with significant risks of rupture and subsequent morbidity. Treatment-related risks may equal or exceed natural history risk, underscoring a critical need for molecularly targeted therapies. A transition towards molecular profiling in recent years has outlined the role of various somatic mutations within endothelial cells in the constitutive activation of cellular proliferation and migration, representing a disease entity distinct from familial syndromes such as hereditary hemorrhagic telangiectasia (HHT) and capillary malformation-AVM (CM-AVM) syndromes. This review summarizes the pathophysiology of bAVM formation, preclinical and clinical evidence for targeted drug treatment, the critical role of combinatorial treatment strategies, and the importance of molecular profiling, ultimately emphasizing the role of genotype-driven care.