Comparative Study of Different Epidermal Growth Factor Receptor (EGFR)-Tyrosine Kinase Inhibitors Affecting Lung Cancer Cell Lines Stably Overexpressing EGFR Mutations

Abstract

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are effective drugs against non-small cell lung cancer (NSCLC) cells harboring common EGFR mutations such as in-frame exon 19 deletions (Del19) and the exon 21 L858R point mutations (L858R). However, currently used EGFR-TKIs are less effective against cells showing uncommon EGFR mutations. Because there is less information available on the sensitivities of the uncommon EGFR mutations, it is important to evaluate the effect of EGFR-TKIs on uncommon mutations. In this study, we sought to establish H1299 NSCLC cell lines stably expressing mutated EGFRs having Del18, G719S, or L861Q that are uncommon mutations as well as Del19 or L858R common mutations, and evaluated whether these cell lines could be applied as a prediction system for the therapeutic effects of EGFR-TKIs. In fact, the levels of phosphorylated EGFR in these cell lines were assessed after treatment with various EGFR-TKIs (4 approved and 4 unapproved drugs). Gefitinib, erlotinib, afatinib, and osimertinib, approved drugs, were effective against Del19, L858R, and L861Q mutations. However, these EGFR-TKIs were less effective against G719S and Del18 mutations. The unapproved drugs neratinib and poziotinib were effective against Del19, L858R, Del18, and L861Q mutations. Interestingly, canertinib and sapitinib had effects against Del19, Del18, and L861Q mutations and no effect against L858R mutation. These results indicate that the established cell lines are suitable for assessing the effects of the EGFR-TKIs on EGFR mutations, including uncommon mutations, and that some of the EGFR-TKIs used are also effective against uncommon mutations.