Additionally, histologic transformation/phenotypic change, including squamous cell carcinoma (SCC) histologic transformation, small-cell lung cancer (SCLC) histologic transformation and epithelial-to-mesenchymal transition (EMT), was a dominant resistance mechanism, particularly in first-line setting, and they suspected that EGFR-independent resistance may emerge earlier than EGFR-dependent resistance (33–36). Here, EGFR is linked to squamous cell carcinoma.