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

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)3657-3661
Number of pages5
JournalCancer Science
Volume109
Issue number11
DOIs
Publication statusPublished - Nov 2018

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Sensitivity of epidermal growth factor receptor with single or double uncommon mutations to afatinib confirmed by a visual assay'. Together they form a unique fingerprint.

  • Cite this