ALK EML4-ALK V1180L

V1180L错义突变在突变筛选中被鉴定，以发现在非小细胞肺癌细胞系中对阿来替尼产生耐药性的突变。该突变对环唑替尼和阿来替尼有耐药性，但对TAE684、西替尼敏感，对布赖卡汀尼敏感度较低。与I1171T相似，它存在于ALK的ATP袋中，可能干扰阿来替尼和环唑替尼的结合，作为一种抵抗机制。
The V1180L missense mutation was identified in a mutagenesis screen to find mutations that conferred resistance to alectinib in a non-small cell lung cancer cell line. This mutation shows resistance to crizotinib and alectinib but sensitivity to TAE684, ceritinib and more mild sensitivity to brigatinib. Similar to I1171T, it resides in the ATP pocket of ALK and likely interferes with alectinib and crizotinib binding as a mechanism of resistance.