Lenvatinib Suppresses Angiogenesis through the Inhibition of both the VEGFR and FGFR Signaling Pathways

Lenvatinib mesilate (lenvatinib) is an oral multiple-receptor tyrosine kinase inhibitor that selectively inhibits the kinase activities of Vascular Endothelial Growth Factor Receptor (VEGFR) 1-3, Fibroblast Growth Factor Receptor (FGFR) 1-4, Platelet-Derived Growth Factor Receptor (PDGFR) α, KIT, and RET. The VEGFR and FGFR signaling pathways are the master regulators of normal and tumor angiogenesis. Lenvatinib showed significant activity in patients with radioiodine-refractory thyroid cancer in a Phase III study and is used in the United States, the European Union, and Japan. Moreover, based on Phase II study, lenvatinib has been approved in the United States for the treatment of patients with advanced renal cell carcinoma in combination with everolimus. In addition, the efficacy of lenvatinib is being evaluated in other cancers, including hepatocellular carcinoma and endometrial cancer. The purpose of this study was to elucidate the mechanism underlying the clinical activities of lenvatinib by using in vitro and in vivo angiogenesis models.