ROS融合基因胆管癌的潜在治疗靶点

目的：寻找ROS激酶抑制剂，探索胆管细胞癌可能的新的治疗靶点。方法应用激酶抑制剂TAE684，评估其对融合基因及其下游效应的抑制作用。结果 TAE684对FIG-ROS（S）、FIG-ROS（L）呈剂量依赖性抑制，IC50分别为10 nM、1．8 nM，并能抑制其下游磷酸化作用。结论 FIG-ROS融合基因受某些抑制剂影响，有望成为治疗胆管癌的新靶点。胆管癌及其他肿瘤如肺癌、恶性胶质瘤中均发现ROS融合基因，临床研究需要更广泛地去筛查肿瘤中激活的ROS激酶。

ROS kinase fusion-a potential therapeutic target in cholangiocarcinoma

Objective To find the kinase inhibitor which works on the FIG-ROS and look for new potential therapeutic target for cholangiocarcinoma.Methods The kinase inhibitor TAE684 was used and its inhibiting ability on FIG-ROS kinase activity and downstream signaling molecules was evaluated.Results Kinase inhibitor TAE684 inhibited FIG-ROS（S）,FIG-ROS（L）in a dose-dependent manner with IC50 10 nM,1.8 nMrespectively.Besides,it could also inhibit the crucial downstream signaling molecules of ROS kinase.Conclusion Our data demonstrates that FIG-ROS can be inhibited by kinase inhibitor,which may be a therapeutic target in cholangiocarcinoma.The iden-tification of ROS tyrosine kinase fusions in cholangiocarcinoma,lung cancer and glioblastoma,tells that a more broadly based screen for acti-vated ROS kinase in cancer is warranted.