TEK and melanoma: Regorafenib may exert a more far-reaching antiangiogenic activity owing to a combined blockade of the VEGFR2 and TIE2 pathways, which is supported by the results from a preclinical study by Tsai and Lee [28] showing a cooperative effect when combining anti-TIE2 and sorafenib, leading to an observed increase in overall survival in a melanoma model.