Sensitivity of epidermal growth factor receptor with single or double uncommon mutations to afatinib confirmed by a visual assay

Shinichi Kimura, Kentaro Tanaka, Taishi Harada, Renpeng Liu, Daisuke Shibahara, Yuko Kawano, Yoichi Nakanishi, Isamu Okamoto

研究成果: ジャーナルへの寄稿記事

抄録

Patients with non-small cell lung cancer (NSCLC) harboring common mutations of the epidermal growth factor receptor (EGFR) are sensitive to EGFR-tyrosine kinase inhibitors (TKI). Although forms of EGFR harboring single uncommon mutations such as G719X or L861Q are thought to be less sensitive to EGFR-TKI, the efficacy of these drugs in patients with double uncommon mutations has remained unclear. We here present an NSCLC patient found to be positive for double uncommon EGFR mutations (G719X and L861Q) by clinical genomic sequencing analysis of a pleural effusion specimen who showed a durable response to the EGFR-TKI afatinib. The sensitivity of EGFR with single or double uncommon mutations to afatinib and the EGFR-TKI erlotinib was also evaluated in vitro with a visual assay based on HEK293 cells transiently transfected with expression plasmids for yellow fluorescent protein (YFP)-tagged fragments of the EGFR intracellular domain (ICD). Whereas forms of EGFR with double uncommon mutations were more sensitive to erlotinib than were those with single uncommon mutations, those with single or double uncommon mutations were similarly sensitive to afatinib, consistent with the patient's clinical outcome. Our data support the notion that afatinib is the most suitable EGFR-TKI for NSCLC harboring uncommon mutations of EGFR. Furthermore, the YFP-EGFR-ICD assay is potentially applicable to prediction of EGFR-TKI efficacy in patients with such mutations.

元の言語英語
ページ(範囲)3657-3661
ページ数5
ジャーナルCancer Science
109
発行部数11
DOI
出版物ステータス出版済み - 11 1 2018

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Epidermal Growth Factor Receptor
Mutation
Protein-Tyrosine Kinases
Non-Small Cell Lung Carcinoma
BIBW 2992
HEK293 Cells
Pleural Effusion
Proteins
Plasmids

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

これを引用

Sensitivity of epidermal growth factor receptor with single or double uncommon mutations to afatinib confirmed by a visual assay. / Kimura, Shinichi; Tanaka, Kentaro; Harada, Taishi; Liu, Renpeng; Shibahara, Daisuke; Kawano, Yuko; Nakanishi, Yoichi; Okamoto, Isamu.

:: Cancer Science, 巻 109, 番号 11, 01.11.2018, p. 3657-3661.

研究成果: ジャーナルへの寄稿記事

Kimura, Shinichi ; Tanaka, Kentaro ; Harada, Taishi ; Liu, Renpeng ; Shibahara, Daisuke ; Kawano, Yuko ; Nakanishi, Yoichi ; Okamoto, Isamu. / Sensitivity of epidermal growth factor receptor with single or double uncommon mutations to afatinib confirmed by a visual assay. :: Cancer Science. 2018 ; 巻 109, 番号 11. pp. 3657-3661.
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