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?

Eri Banno, Yosuke Togashi, Yu Nakamura, Masato Chiba, Yoshihisa Kobayashi, Hidetoshi Hayashi, Masato Terashima, Marco A. de Velasco, Kazuko Sakai, Yoshihiko Fujita, Tetsuya Mitsudomi, Kazuto Nishio

Research output: Contribution to journalArticlepeer-review

57 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1134-1140
Number of pages7
JournalCancer Science
Volume107
Issue number8
DOIs
Publication statusPublished - Aug 1 2016
Externally publishedYes

Keywords

  • Afatinib
  • epidermal growth factor receptor-tyrosine kinase inhibitors
  • L861Q
  • S768I
  • uncommon epidermal growth factor receptor mutation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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