Antitumor activities of the targeted multi-tyrosine kinase inhibitor lenvatinib (E7080) against RET gene fusion-driven tumor models

作者：Okamoto Kiyoshi^*; Kodama Kotaro; Takase Kazuma; Sugi Naoko Hata; Yamamoto Yuji; Iwata Masao; Tsuruoka Akihiko

来源：Cancer Letters, 2013, 340(1): 97-103.

DOI：10.1016/j.canlet.2013.07.007

• Lenvatinib
• RET inhibitor
• Anti-cancer drug
• Xenograft model
• Lung cancer
• Thyroid cancer

RET gene fusions are recurrent oncogenes identified in thyroid and lung carcinomas. Lenvatinib is a multi-tyrosine kinase inhibitor currently under evaluation in several clinical trials. Here we evaluated lenvatinib in RET gene fusion-driven preclinical models. In cellular assays, lenvatinib inhibited autophosphorylation of KIF5B-RET. CCDC6-RET, and NcoA4-RET. Lenvatinib suppressed the growth of CCDC6-RET human thyroid and lung cancer cell lines, and as well, suppressed anchorage-independent growth and tumorigenicity of RET gene fusion-transformed NIH3T3 cells. These results demonstrate that lenvatinib can exert antitumor activity against RET gene fusion-driven tumor models by inhibiting oncogenic RET gene fusion signaling.

• 出版日期2013-10-28