Abnormalities of epidermal growth

factor receptor (EGFR) in non-small-cell lung cancer (NSCLC) patients consist of EGFR overexpression and EGFR (HER1) gene mutations. Structural dysfunction of the tyrosine kinase domain of EGFR is associated with the clinical response to tyrosine kinase inhibitors (TKI) in patients with NSCLC. The most common EGFR genemutations occur as either deletions in exon 19 or as substitution L858R in exon 21 and cause a clinically beneficial response to gefinitib or erlotinib treat-ment. Unfortunately, the majority of patients finally develop resistance to these drugs. Acquired resistance is linked to secondary mutations localised in the EGFR gene, mainly substitution T790M in exon 20. Through intense research a few differentmechanisms of resistance to reversible tyrosine kinase inhibitors have been identified: amplification ofMET or IGF-1R genes, abnormalities of PTEN andmTOR proteins as well as rare muta-tions in EGFR andHER2 genes. Extensively investigated new drugs could be of sig-nificant efficiency in NSCLC patients with secondary resistance to reversible EGFR TKI. Key words: epidermal growth facto