EGFR and non-small cell lung carcinoma: To gain insight into the potential mechanisms underlying osimertinib resistance, we established EGFR-mutant cell lines using human NSCLC A549 cells, which originally possessed wild-type EGFR. The CRISPR/Cas9 system was utilized to delete the endogenous EGFR gene (Supplementary Fig. 1), and various EGFR variants, including wild-type (WT) EGFR, EGFR19del747_750 (19D), EGFR19del747_750+T790M (19DM), EGFR19del747_750+T790M+C797S (19DMS), EGFRL858R (R), EGFRL858R+T790M (RM), and EGFRL858R+T790M+C797S (RMS), were subsequently introduced (Supplementary Fig. 2a, b).