title: Sensitivities to various epidermal growth factor receptor-tyrosine kinase inhibitors of uncommon epidermal growth factor receptor mutations L861Q and S768I: What is the optimal epidermal growth factor receptor-tyrosine kinase inhibitor?
abstract: Most patients with non-small cell lung cancer (NSCLC) harboring common epidermal growth factor receptor (EGFR) mutations, such as deletions in exon 19 or the L858R mutation in exon 21, respond dramatically to EGFR tyrosine kinase inhibitors (EGFR-TKI), and their sensitivities to various EGFR-TKI have been well characterized. Our previous article showed the in vitro sensitivities of EGFR exon 18 mutations to EGFR-TKI, but little information regarding the sensitivities of other uncommon EGFR mutations is available. First, stable transfectant Ba/F3 cell lines harboring EGFR L858R (Ba/F3-L858R), L861Q (Ba/F3-L861Q) or S768I (Ba/F3-S768I) mutations were created and their drug sensitivities to various EGFR-TKI were examined. Both the Ba/F3-L861Q and Ba/F3-S768I cell lines were less sensitive to erlotinib, compared with the Ba/F3-L858R cell line, but their sensitivities to afatinib were similar to that of the Ba/F3-L858R cell line. The Ba/F3-L861Q cell line was similarly sensitive and the Ba/F3-S768I cell line was less sensitive to osimertinib, compared with the Ba/F3-L858R cell line. The results of western blot analyses were consistent with these sensitivities. Next, similar experiments were also performed using the KYSE270 (L861Q) and KYSE 450 (S768I) cell lines, and their results were compatible with those of the transfectant Ba/F3 cell lines. Our findings suggest that NSCLC harboring the EGFR L861Q mutation might be sensitive to afatinib or osimertinib and that NSCLC harboring the EGFR S768I mutation might be sensitive to afatinib. Overall, afatinib might be the optimal EGFR-TKI against these uncommon EGFR mutations.
authors.affiliation: Department of Genome Biology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Banno
authors.affiliation: Department of Genome Biology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Togashi
authors.affiliation: Department of Genome Biology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Department of Genome Biology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan.|Department of Thoracic Surgery, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Chiba
authors.affiliation: Department of Thoracic Surgery, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Kobayashi
authors.affiliation: Department of Genome Biology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan.|Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Hayashi
authors.affiliation: Department of Genome Biology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Terashima
authors.affiliation: Department of Genome Biology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan.
authors.forename: Marco A
authors.initials: MA
authors.lastname: de Velasco
authors.affiliation: Department of Genome Biology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Sakai
authors.affiliation: Department of Genome Biology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Fujita
authors.affiliation: Department of Thoracic Surgery, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mitsudomi
authors.affiliation: Department of Genome Biology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan.
authors.forename: Kazuto
authors.initials: K
authors.lastname: Nishio
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D002460:Cell Line; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D050505:Mutant Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics*; D009154:Mutation; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D014162:Transfection
chemical_list: D050505:Mutant Proteins; D015513:Oncogene Proteins; D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors
keywords: Afatinib; L861Q; S768I; epidermal growth factor receptor-tyrosine kinase inhibitors; uncommon epidermal growth factor receptor mutation