EGFR AND KRAS MUTATIONS IMPORTANT FOR NON-SMALL CELL LUNG CANCER TARGET THERAPY

Last successful results in target therapy of cancer were achieved with different tyrosine kinases inhibitors (TKI). Target therapy of non-small cell lung cancer (NSCLC) with EGFR inhibitors gefitinib and erlotinib is effective only in patients with somatic mutations in EGFR gene. We have studied mutations in 18, 19 and 21 exons of EGFR in tumor DNA from 214 NSCLC patients, including 186 adenocarcinomas (ADC). Mutations were found in 29% (54/186) ADCs, more frequently in women (p=0,0006), predominantly in nonsmokers (p=0,0002). There were 746ELREA750 deletions in exon 19, point mutation L858R in exon 21 and mutations in codons G719 and E709 in exon 18 of EGFR. Besides, we have revealed «non-ELREA» mutations in EGFR exon 19, which had uncertain clinical significance. TKI therapy is non-effective in NSCLC patients with KRAS mutations. Mutations in KRAS exon 2 were found in 11% of ADC, more frequently in men and smokers, the frequency of G12C mutations was elevated. Thus the EGFR/KRAS mutation spectrums differed in never smokers and heavy smokers NSCLC patients. Analysis of EGFR/KRAS mutations is necessary for individualization of TKI therapy in NSCLC patients.