E7080, known as
lenvatinib, is an oral multitargeted
tyrosine kinase inhibitor that has been shown to improve the survival rate of patients with radioiodine-refractory
thyroid cancer. However, a majority of patients do not continue
lenvatinib intake due to
disease progression or significant toxicity. To improve treatment success rates, we propose the combination of
lenvatinib with
mitogen-activated protein kinase (
MEK) inhibitors. To test this hypothesis, we tested the effects of
lenvatinib with the
MEK inhibitor
U0126 in vitro using two human
anaplastic thyroid cancer (ATC) cell lines, 8505C and TCO1, and with another
MEK inhibitor,
selumetinib (
AZD6244), in an ATC mouse model. We found that the combination of
lenvatinib with
MEK inhibitors enhanced the antitumor effects of monotherapy with either agent in vitro and in vivo, and these effects may be through the AKT (
Protein Kinase B) and
extracellular signal-regulated kinase (ERK) signaling pathways. Furthermore, the combination does not have significant adverse effects in the ATC mouse models in terms of
body weight, blood biochemical parameters, and histopathology. In conclusion, the combination of
lenvatinib with an
MEK inhibitor is a potentially viable therapeutic approach for ATC treatment.