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• W2184959883 abstract "Human epidermal growth factor receptor 2 ( HER 2) is a member of the HER family of proteins containing four receptor tyrosine kinases. It plays an important role in the pathogenesis of certain human cancers. In non‐small‐cell lung cancer ( NSCLC ), HER 2 amplification or mutations have been reported. However, little is known about the benefit of HER 2‐targeted therapy for NSCLC s harboring HER 2 alterations. In this study, we investigated the antitumor effect of afatinib, an irreversible epidermal growth factor receptor ( EGFR )– HER 2 dual inhibitor, in lung cancers harboring HER 2 oncogene alterations, including novel HER 2 mutations in the transmembrane domain, which we recently identified. Normal bronchial epithelial cells, BEAS ‐2B, ectopically overexpressing wild‐type HER 2 or mutants (A775ins YVMA , G776 VC , G776 LC , P780ins GSP , V659E, and G660D) showed constitutive autophosphorylation of HER 2 and activation of downstream signaling. They were sensitive to afatinib, but insensitive to gefitinib. Furthermore, we examined the antitumor activity of afatinib and gefitinib in several NSCLC cell lines, and investigated the association between their genetic alterations and sensitivity to afatinib treatment. In HER 2 ‐altered NSCLC cells (H2170, Calu‐3, and H1781), afatinib downregulated the phosphorylation of HER 2 and EGFR as well as their downstream signaling, and induced an antiproliferative effect through G 1 arrest and apoptotic cell death. In contrast, HER 2 ‐ or EGFR ‐non‐dependent NSCLC cells were insensitive to afatinib. In addition, these effects were confirmed in vivo by using a xenograft mouse model of HER 2 ‐altered lung cancer cells. Our results suggest that afatinib is a therapeutic option as a HER 2‐targeted therapy for NSCLC harboring HER 2 amplification or mutations." @default.
• W2184959883 created "2016-06-24" @default.
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• W2184959883 date "2015-12-03" @default.
• W2184959883 modified "2023-10-04" @default.
• W2184959883 title "Antitumor effect of afatinib, as a human epidermal growth factor receptor 2‐targeted therapy, in lung cancers harboring <i> <scp>HER</scp> 2 </i> oncogene alterations" @default.
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• W2184959883 doi "https://doi.org/10.1111/cas.12845" @default.
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