An in vivo model of EGFR acquired resistance was obtained by treating nude mice xenografted with HCC827, a human NSCLC cell line harboring the EGFR activating mutation (del ex19), with a sequence of first-generation EGFR-TKIs (erlotinib and gefitinib) (step 1), second-generation EGFR-TKIs (afatinib) plus/minus cetuximab, anti-EGFR monoclonal antibody (step 2) and third-generation EGFR-TKIs (osimertinib) (step 3) (Figure 1). This evidence concerns the gene EGFR and non-small cell lung carcinoma.