Tumor biopsies upon progression on EGFR TKI treatment have shown overexpression or amplification of HER2 and MET, and mutations in BRAF and PIK3CA.2,4 The third mechanism involves morphological alterations: dedifferentiation by epidermal-mesenchymal transition (EMT) or change to small-cell-lung carcinoma (SCLC), including RB1 loss.2,4. The gene discussed is EGFR; the disease is small cell lung carcinoma.