Considering that therapy with afatinib plus cetuximab or osimertinib can be effective in EGFR-TKI resistant tumors [10, 11, 20, 21], the present work studied the efficacy of sequential treatment with various anti-EGFR agents and the molecular mechanisms of tumor evolution and drug resistance in EGFR-mutant lung cancer models. Here, EGFR is linked to lung carcinoma.