ALK and squamous cell lung carcinoma: In addition, various ALK-independent mechanisms underlying acquired resistance to ALK-TKIs have been identified, including bypass tract activations through EGFR, HER2/HER3, IGF-1R, MET, or RAF-MEK as mechanisms of “off target” resistance, epithelial–mesenchymal transition, and small cell and squamous cell lung cancer transformations as “phenotypic changes” of acquired resistance3.