EML4-ALK Mutations in Lung Cancer That Confer Resistance to ALK Inhibitors
EML4-ALK Mutations in Lung Cancer That Confer Resistance to ALK Inhibitors
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DOI：
10.1056/nejmoa1007478
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发表时间：
2010-10-28
影响因子：
158.5
通讯作者：
Mano, Hiroyuki
中科院分区：
文献类型：
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作者：
Choi, Young Lim;Soda, Manabu;Mano, Hiroyuki
EML4（棘皮微管相关蛋白样4）-ALK（间变性淋巴瘤激酶）融合型酪氨酸激酶是一种在4%至5%的非小细胞肺癌中发现的癌蛋白，ALK特异性抑制剂治疗此类肿瘤的临床试验目前正在进行中。在这里，我们报告了在用ALK抑制剂治疗复发期从患者分离的肿瘤细胞中发现的EML4-ALK激酶结构域内的两个继发性突变。每个突变在肿瘤的亚克隆中独立发展，并赋予对两种不同的ALK抑制剂的显着抗性。
The EML4 (echinoderm microtubule-associated protein-like 4)-ALK (anaplastic lymphoma kinase) fusion-type tyrosine kinase is an oncoprotein found in 4 to 5% of non-small-cell lung cancers, and clinical trials of specific inhibitors of ALK for the treatment of such tumors are currently under way. Here, we report the discovery of two secondary mutations within the kinase domain of EML4-ALK in tumor cells isolated from a patient during the relapse phase of treatment with an ALK inhibitor. Each mutation developed independently in subclones of the tumor and conferred marked resistance to two different ALK inhibitors.