The indications of targeted therapies may begin bleeding into broader domains. Last week’s NEJM report describes a whole-exome fishing expedition among 26 patients with sporadic arteriovenous malformations (AVM). The authors caught some somatic KRAS mutations and went on to prospectively validate their presence in an additional 16 of 33 Finnish patients with sporadic AVMs. We care because this identifies constitutive activation of the MAPK-ERK pathway as a common culprit of sporadic AVM generation, which means already formulated MEK inhibitors could offer an AVM treatment in the form of a small molecule. Mind. Blown.