- Vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) signal transduction pathways have synergistic effects on promoting angiogenesis and growth factor expression. Hypoxia caused by treatment with VEGF inhibitors results in the upregulation of c-MET, the receptor for HGF. In a mouse model, combined blockade of VEGFR and c-Met significantly prolonged survival compared with inhibition of either target alone.