Mutations involving EGFR gene
Somatic mutations involving the EGFR (Epidermal Growth Factor Receptor) tyrosine kinase domain confer susceptibility to therapeutic molecules (gefitinib and erlotinib), approved for the treatment of NSCLC (Non-Small Cell Lung Cancer). These mutations consist of small nucleotide deletions or substitutions in exons 18, 19, 20 and 21 of the EGFR gene, and occur in 10-19% of patients with NSCLC, with female, non-smokers, adenocarcinoma histology predominance.
EGFR mutations conferring sensitivity to the tyrosine kinase inhibitors are grouped near the ATP cleft of this domain, where the amino acids mediate the binding of 4-anilinoquinazoline compounds, such as gefitinib and erlotinib. Thus, the increased sensitivity to inhibitors of tyrosine kinase associated with EGFR mutations can substantially contribute to the clinical response in certain patients with small cell lung carcinoma.
