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Continuous inhibition of epidermal growth factor receptor phosphorylation by erlotinib enhances antitumor activity of chemotherapy in erlotinib-resistant tumor xenografts

  • Authors:
    • Toshiki Iwai
    • Yoichiro Moriya
    • Masatoshi Shirane
    • Kaori Fujimoto-Ouchi
    • Kazushige Mori
  • View Affiliations / Copyright

    Affiliations: Product Research Department, Chugai Pharmaceutical Co., Ltd., 200 Kajiwara, Kamakura 247-8530, Japan
    Copyright: © Iwai et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 923-928
    |
    Published online on: December 30, 2011
       https://doi.org/10.3892/or.2011.1614
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Abstract

Erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor, has been shown to have benefits for non-small cell lung cancer and pancreatic cancer patients; however, almost all patients develop progressive disease during the therapy. On the other hand, it has been reported that a tumor continues to express epidermal growth factor receptor even after developing progressive disease. To demonstrate the clinical relevance of erlotinib treatment after progressive disease, we investigated whether continuous administration of erlotinib in combination with chemotherapy has a useful effect on progressive disease development during erlotinib treatment. For this purpose, we examined the antitumor effect of a combination therapy of a chemotherapeutic agent with erlotinib using two types of erlotinib-resistant tumor xenograft models: a non-small cell lung cancer model, in which EBC-1, H1975 and HCC827TR3 tumors were implanted, and an HPAC pancreatic cancer cell xenograft which generates erlotinib-resistant tumors in vivo. As a result, the combination therapy showed a significantly higher antitumor activity compared with chemomonotherapy in all xenograft models except the H1975 xenografts. Furthermore, erlotinib alone suppressed the phosphorylation of epidermal growth factor receptor in HPAC tumors and the two non-small cell lung cancer cell lines other than H1975. Therefore, combination therapy which uses erlotinib can be considered effective if epidermal growth factor receptor phosphorylation is inhibited by erlotinib, even in erlotinib-resistant tumor xenograft models. Our results suggest that the continuous inhibition of epidermal growth factor receptor phosphorylation by erlotinib after progressive disease enhances the antitumor activity of chemotherapy.
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Copy and paste a formatted citation
Spandidos Publications style
Iwai T, Moriya Y, Shirane M, Fujimoto-Ouchi K and Mori K: Continuous inhibition of epidermal growth factor receptor phosphorylation by erlotinib enhances antitumor activity of chemotherapy in erlotinib-resistant tumor xenografts. Oncol Rep 27: 923-928, 2012.
APA
Iwai, T., Moriya, Y., Shirane, M., Fujimoto-Ouchi, K., & Mori, K. (2012). Continuous inhibition of epidermal growth factor receptor phosphorylation by erlotinib enhances antitumor activity of chemotherapy in erlotinib-resistant tumor xenografts. Oncology Reports, 27, 923-928. https://doi.org/10.3892/or.2011.1614
MLA
Iwai, T., Moriya, Y., Shirane, M., Fujimoto-Ouchi, K., Mori, K."Continuous inhibition of epidermal growth factor receptor phosphorylation by erlotinib enhances antitumor activity of chemotherapy in erlotinib-resistant tumor xenografts". Oncology Reports 27.4 (2012): 923-928.
Chicago
Iwai, T., Moriya, Y., Shirane, M., Fujimoto-Ouchi, K., Mori, K."Continuous inhibition of epidermal growth factor receptor phosphorylation by erlotinib enhances antitumor activity of chemotherapy in erlotinib-resistant tumor xenografts". Oncology Reports 27, no. 4 (2012): 923-928. https://doi.org/10.3892/or.2011.1614
Copy and paste a formatted citation
x
Spandidos Publications style
Iwai T, Moriya Y, Shirane M, Fujimoto-Ouchi K and Mori K: Continuous inhibition of epidermal growth factor receptor phosphorylation by erlotinib enhances antitumor activity of chemotherapy in erlotinib-resistant tumor xenografts. Oncol Rep 27: 923-928, 2012.
APA
Iwai, T., Moriya, Y., Shirane, M., Fujimoto-Ouchi, K., & Mori, K. (2012). Continuous inhibition of epidermal growth factor receptor phosphorylation by erlotinib enhances antitumor activity of chemotherapy in erlotinib-resistant tumor xenografts. Oncology Reports, 27, 923-928. https://doi.org/10.3892/or.2011.1614
MLA
Iwai, T., Moriya, Y., Shirane, M., Fujimoto-Ouchi, K., Mori, K."Continuous inhibition of epidermal growth factor receptor phosphorylation by erlotinib enhances antitumor activity of chemotherapy in erlotinib-resistant tumor xenografts". Oncology Reports 27.4 (2012): 923-928.
Chicago
Iwai, T., Moriya, Y., Shirane, M., Fujimoto-Ouchi, K., Mori, K."Continuous inhibition of epidermal growth factor receptor phosphorylation by erlotinib enhances antitumor activity of chemotherapy in erlotinib-resistant tumor xenografts". Oncology Reports 27, no. 4 (2012): 923-928. https://doi.org/10.3892/or.2011.1614
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