ALK EML4-ALK

由alk激酶域（外显子20-29）组成的eml4-alk融合变体1融合到eml4外显子1-13是最常见的eml4-alk变体，在非小细胞肺癌中被发现。多个EML4断点的剃除被描述为对抑制剂的不同敏感性，变异1在细胞系中显示出比3a更高的敏感性。EML4-ALK对环唑天宁敏感；然而，在案例研究中已经描述了几种引起耐药性突变的突变。在环唑替尼唯一的临床试验中，包括在受试者亚群中测定EML4-ALK变异体类型，观察到非常高的应答率，尽管这些数字不足以验证变异体类型与结果的相关性。这种变异的临床前研究表明对hsp90抑制剂敏感。
The EML4-ALK fusion variant 1 consisting of ALK kinase domain (exons 20-29) fused to EML4 exons 1-13 is the most common EML4-ALK variant, and was discovered in non-small cell lung cancer. Multiple EML4 breakpoint shave been described with differential sensitivity to inhibitors with variant 1 showing greater sensitivity than 3a in cell lines. EML4-ALK is crizotinib sensitive; however, several mutations that confer resistance mutations have been described in case studies. In the only clinical trial for crizotinib that included determination of EML4-ALK variant type in a subset of its participants, a very high response rate was observed, although the numbers were insufficient to validate correlation of variant type to outcome. Preclinical studies with this variant have indicated sensitivity to Hsp90 inhibitors.