This finding suggests a mechanism by which angiosarcomas could develop adaptive resistance to VEGFR-targeted therapy.86 In addition to PLCG1 mutations, mutations or amplifications in K-, H-, and N-RAS, B- and C-RAF, and MAPK1 were identified in angiosarcoma.87 Preclinical studies with canine angiosarcomas have demonstrated anti-tumor activity with MEK inhibition.88 This evidence concerns the gene KDR and angiosarcoma.