EGFR and non-small cell lung carcinoma: A second mutational event in EGFR, the T790M substitution in exon 20, is thought to account for more than half of all cases of acquired resistance to first-generation EGFR inhibitors in NSCLC.46 It was initially predicted that the mechanism of resistance underlying the T790M mutation was steric hindrance imposed by the presence of a bulky methionine residue that would prevent the binding of first-generation EGFR inhibitors to EGFR.