Eisai Co., Ltd., Tokodai 5-1-3, Tsukuba, Ibaraki, 300-2635, Japan.
Cancer Lett. 2013 Oct 28;340(1):97-103. doi: 10.1016/j.canlet.2013.07.007. Epub 2013 Jul 12.
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 auto-phosphorylation 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.
RET 基因融合是在甲状腺癌和肺癌中发现的常见致癌基因。仑伐替尼是一种多靶点酪氨酸激酶抑制剂，目前正在多项临床试验中进行评估。在这里，我们评估了仑伐替尼在 RET 基因融合驱动的临床前模型中的作用。在细胞检测中，仑伐替尼抑制 KIF5B-RET、CCDC6-RET 和 NcoA4-RET 的自身磷酸化。仑伐替尼抑制 CCDC6-RET 人甲状腺和肺癌细胞系的生长，同时抑制 RET 基因融合转化的 NIH3T3 细胞的无锚定依赖性生长和致瘤性。这些结果表明，仑伐替尼通过抑制致癌的 RET 基因融合信号，对 RET 基因融合驱动的肿瘤模型发挥抗肿瘤活性。
