Broadly three mechanisms of acquired resistance to EGFR-TKIs have been reported [37]: (1) alteration of the target via EGFR-TKI susceptibility mutations (acquiring T790M mutation), (2) activation of alternative pathways due to genetic alterations such as MET amplification and KRAS mutation, and (3) alteration of the phenotype, such as transformation to small cell lung cancer or EMT (epithelial-mesenchymal transition). The gene discussed is KRAS; the disease is small cell lung carcinoma.