Over the past years, EGFR tyrosine kinase inhibitors (TKI) revolutionized treatment response. 1stgeneration (reversible) EGFR TKI and later the 2nd –generation irreversible EGFR TKI Afatinib were aimed to improve treatment response. Nevertheless, diverse resistance mechanisms develop within the first year of therapy. | Mutational spectrum of acquired resistance to reversible versus irreversible EGFR tyrosine kinase inhibitors