Antitumor activities of the targeted multi-tyrosine kinase inhibitor lenvatinib (E7080) against RET gene fusion-driven tumor models
Antitumor activities of the targeted multi-tyrosine kinase inhibitor lenvatinib (E7080) against RET gene fusion-driven tumor models
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DOI：
10.1016/j.canlet.2013.07.007
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发表时间：
2013-10-28
期刊：
影响因子：
9.7
通讯作者：
Tsuruoka, Akihiko
中科院分区：
文献类型：
--
作者：
Okamoto, Kiyoshi;Kodama, Kotaro;Tsuruoka, Akihiko
RET基因融合是在甲状腺癌和肺癌中发现的复发癌基因。Lenvatinib是一种多酪氨酸激酶抑制剂，目前正在多项临床试验中进行评估。我们在RET基因融合驱动的临床前模型中评估了乐伐替尼。在细胞试验中，乐伐替尼可抑制KIF 5 B-RET的自磷酸化。CCDC 6-RET和NcoA 4-RET。乐伐替尼可抑制CCDC 6-RET人甲状腺癌和肺癌细胞系的生长，也可抑制RET基因融合转化的NIH 3 T3细胞的锚定非依赖性生长和致瘤性。这些结果表明，乐伐替尼可通过抑制致癌RET基因融合信号传导，对RET基因融合驱动的肿瘤模型发挥抗肿瘤活性。(C)2013作者由爱思唯尔有限公司出版。保留所有权利。
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.