Journal
CANCER LETTERS
Volume 340, Issue 1, Pages 97-103Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2013.07.007
Keywords
Lenvatinib; RET inhibitor; Anti-cancer drug; Xenograft model; Lung cancer; Thyroid cancer
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Funding
- Eisai, Co., Ltd.
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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. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved.
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