論文

査読有り 国際誌
2019年3月

Anti-tumor effect of neratinib against lung cancer cells harboring HER2 oncogene alterations.

Oncology letters
  • Yusuke Ogoshi
  • ,
  • Kazuhiko Shien
  • ,
  • Takahiro Yoshioka
  • ,
  • Hidejiro Torigoe
  • ,
  • Hiroki Sato
  • ,
  • Masakiyo Sakaguchi
  • ,
  • Shuta Tomida
  • ,
  • Kei Namba
  • ,
  • Eisuke Kurihara
  • ,
  • Yuta Takahashi
  • ,
  • Ken Suzawa
  • ,
  • Hiromasa Yamamoto
  • ,
  • Junichi Soh
  • ,
  • Shinichi Toyooka

17
3
開始ページ
2729
終了ページ
2736
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.3892/ol.2019.9908

Human epidermal growth factor receptor 2 (HER2) is a member of the ErbB family of receptor tyrosine kinases. Numerous studies have reported the amplification and overexpression of HER2 in several types of cancer, including non-small cell lung cancer (NSCLC). However, the benefits of HER2-targeted therapy have not been fully established. In the present study, the anti-tumor effect of neratinib, an irreversible pan-HER tyrosine kinase inhibitor (TKI), against NSCLC cells harboring HER2 alterations was investigated. The sensitivity of normal bronchial epithelial cells (BEAS-2B) ectopically overexpressing wild-type or mutant HER2 to neratinib was assessed. Furthermore, the anti-tumor activity of neratinib in several NSCLC cell lines harboring HER2 alterations was determined in vitro and in vivo, and the association between their genetic alterations and sensitivity to neratinib treatment was investigated. BEAS-2B cells ectopically overexpressing wild-type HER2 or mutants (A775insYVMA, G776VC, G776LC, P780insGSP, V659E, G660D and S310F) exhibited constitutive autophosphorylation of HER2, as determined by western blotting. While these BEAS-2B cells were sensitive to neratinib, they were insensitive to erlotinib, a first-generation epidermal growth factor receptor-TKI. Neratinib also exerted anti-proliferative effects on HER2-altered (H2170, Calu-3 and H1781) NSCLC cell lines. Neratinib was also demonstrated to exert strong tumor growth inhibitory activity in mouse xenograft models using HER2-altered lung cancer cells. The results of the present study strongly suggest that neratinib has potential as a promising therapeutic option for the treatment of HER2-altered NSCLC.

リンク情報
DOI
https://doi.org/10.3892/ol.2019.9908
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/30854046
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365915
ID情報
  • DOI : 10.3892/ol.2019.9908
  • ISSN : 1792-1074
  • PubMed ID : 30854046
  • PubMed Central 記事ID : PMC6365915

エクスポート
BibTeX RIS