Tumors are capable of continued survival, growth, and proliferation in the setting of persistent VEGFR2 inhibition by several mechanisms including a) activating alternative, compensatory pathways that can continue to support tumor neovascularization and b) reprogramming tumor cells so that they become more invasive, invade deeper into normal tissue, and thus survive using the normal, physiologic vasculature. Ang = angiopoietin, VEGF = vascular epithelial growth factor, VEGFR = vascular epithelial growth factor receptor, TKI = tyrosine kinase inhibitor, HGF = hepatocyte growth factor.