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

  • Authors:
    • 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
  • View Affiliations / Copyright

    Affiliations: Department of Thoracic, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700‑8558, Japan, Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700‑8558, Japan, Department of Biobank, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700‑8558, Japan
    Copyright: © Ogoshi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2729-2736
    |
    Published online on: January 8, 2019
       https://doi.org/10.3892/ol.2019.9908
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Abstract

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.
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Copy and paste a formatted citation
Spandidos Publications style
Ogoshi Y, Shien K, Yoshioka T, Torigoe H, Sato H, Sakaguchi M, Tomida S, Namba K, Kurihara E, Takahashi Y, Takahashi Y, et al: Anti‑tumor effect of neratinib against lung cancer cells harboring HER2 oncogene alterations. Oncol Lett 17: 2729-2736, 2019.
APA
Ogoshi, Y., Shien, K., Yoshioka, T., Torigoe, H., Sato, H., Sakaguchi, M. ... Toyooka, S. (2019). Anti‑tumor effect of neratinib against lung cancer cells harboring HER2 oncogene alterations. Oncology Letters, 17, 2729-2736. https://doi.org/10.3892/ol.2019.9908
MLA
Ogoshi, Y., Shien, K., Yoshioka, T., Torigoe, H., Sato, H., Sakaguchi, M., Tomida, S., Namba, K., Kurihara, E., Takahashi, Y., Suzawa, K., Yamamoto, H., Soh, J., Toyooka, S."Anti‑tumor effect of neratinib against lung cancer cells harboring HER2 oncogene alterations". Oncology Letters 17.3 (2019): 2729-2736.
Chicago
Ogoshi, Y., Shien, K., Yoshioka, T., Torigoe, H., Sato, H., Sakaguchi, M., Tomida, S., Namba, K., Kurihara, E., Takahashi, Y., Suzawa, K., Yamamoto, H., Soh, J., Toyooka, S."Anti‑tumor effect of neratinib against lung cancer cells harboring HER2 oncogene alterations". Oncology Letters 17, no. 3 (2019): 2729-2736. https://doi.org/10.3892/ol.2019.9908
Copy and paste a formatted citation
x
Spandidos Publications style
Ogoshi Y, Shien K, Yoshioka T, Torigoe H, Sato H, Sakaguchi M, Tomida S, Namba K, Kurihara E, Takahashi Y, Takahashi Y, et al: Anti‑tumor effect of neratinib against lung cancer cells harboring HER2 oncogene alterations. Oncol Lett 17: 2729-2736, 2019.
APA
Ogoshi, Y., Shien, K., Yoshioka, T., Torigoe, H., Sato, H., Sakaguchi, M. ... Toyooka, S. (2019). Anti‑tumor effect of neratinib against lung cancer cells harboring HER2 oncogene alterations. Oncology Letters, 17, 2729-2736. https://doi.org/10.3892/ol.2019.9908
MLA
Ogoshi, Y., Shien, K., Yoshioka, T., Torigoe, H., Sato, H., Sakaguchi, M., Tomida, S., Namba, K., Kurihara, E., Takahashi, Y., Suzawa, K., Yamamoto, H., Soh, J., Toyooka, S."Anti‑tumor effect of neratinib against lung cancer cells harboring HER2 oncogene alterations". Oncology Letters 17.3 (2019): 2729-2736.
Chicago
Ogoshi, Y., Shien, K., Yoshioka, T., Torigoe, H., Sato, H., Sakaguchi, M., Tomida, S., Namba, K., Kurihara, E., Takahashi, Y., Suzawa, K., Yamamoto, H., Soh, J., Toyooka, S."Anti‑tumor effect of neratinib against lung cancer cells harboring HER2 oncogene alterations". Oncology Letters 17, no. 3 (2019): 2729-2736. https://doi.org/10.3892/ol.2019.9908
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