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Antitumor activity of erlotinib in combination with gemcitabine in in vitro and in vivo models of KRAS-mutated pancreatic cancers

  • Authors:
    • Koh Furugaki
    • Toshiki Iwai
    • Kumiko Kondoh
    • Yoichiro Moriya
    • Kazushige Mori
  • View Affiliations / Copyright

    Affiliations: Product Research Department, Kamakura Research Laboratories, Chugai Pharmaceutical Co., Ltd., Kanagawa 247-8530, Japan
  • Pages: 231-235
    |
    Published online on: March 1, 2010
       https://doi.org/10.3892/ol_00000041
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Abstract

Erlotinib treatment in combination with gemcitabine is a standard therapy for patients with locally advanced pancreatic cancer in many countries, including the US and the EU. Since mutations of the K-ras oncogene (KRAS) occur in approximately 90% of pancreatic cancers, we examined the antitumor activity of erlotinib in combination with gemcitabine in KRAS-mutated pancreatic cancer cell lines, HPAC and Capan-1, which have the KRAS mutation G12D and G12V, respectively. We analyzed the mode of inhibition of in vitro tumor cell proliferation by means of a combination index and found that a combination treatment of erlotinib plus gemcitabine had an additive effect in the two cell lines. We then examined the effect of erlotinib and gemcitabine on the phosphorylation of epidermal growth factor receptor (EGFR). Erlotinib strongly suppressed, while gemcitabine augmented the phosphorylation of EGFR, which was completely blocked by erlotinib in the two cell lines. An in vivo tumor growth inhibition test was then performed using the HPAC tumor xenograft model. The combination therapy of erlotinib and gemcitabine resulted in a significant inhibition of tumor growth compared with erlotinib or gemcitabine monotherapy. To the best of our knowledge, this is the first study to show the combination effect of erlotinib and gemcitabine in vivo using a xenograft model of a KRAS-mutated pancreatic cancer cell line.
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Copy and paste a formatted citation
Spandidos Publications style
Furugaki K, Iwai T, Kondoh K, Moriya Y and Mori K: Antitumor activity of erlotinib in combination with gemcitabine in in vitro and in vivo models of KRAS-mutated pancreatic cancers . Oncol Lett 1: 231-235, 2010.
APA
Furugaki, K., Iwai, T., Kondoh, K., Moriya, Y., & Mori, K. (2010). Antitumor activity of erlotinib in combination with gemcitabine in in vitro and in vivo models of KRAS-mutated pancreatic cancers . Oncology Letters, 1, 231-235. https://doi.org/10.3892/ol_00000041
MLA
Furugaki, K., Iwai, T., Kondoh, K., Moriya, Y., Mori, K."Antitumor activity of erlotinib in combination with gemcitabine in in vitro and in vivo models of KRAS-mutated pancreatic cancers ". Oncology Letters 1.2 (2010): 231-235.
Chicago
Furugaki, K., Iwai, T., Kondoh, K., Moriya, Y., Mori, K."Antitumor activity of erlotinib in combination with gemcitabine in in vitro and in vivo models of KRAS-mutated pancreatic cancers ". Oncology Letters 1, no. 2 (2010): 231-235. https://doi.org/10.3892/ol_00000041
Copy and paste a formatted citation
x
Spandidos Publications style
Furugaki K, Iwai T, Kondoh K, Moriya Y and Mori K: Antitumor activity of erlotinib in combination with gemcitabine in in vitro and in vivo models of KRAS-mutated pancreatic cancers . Oncol Lett 1: 231-235, 2010.
APA
Furugaki, K., Iwai, T., Kondoh, K., Moriya, Y., & Mori, K. (2010). Antitumor activity of erlotinib in combination with gemcitabine in in vitro and in vivo models of KRAS-mutated pancreatic cancers . Oncology Letters, 1, 231-235. https://doi.org/10.3892/ol_00000041
MLA
Furugaki, K., Iwai, T., Kondoh, K., Moriya, Y., Mori, K."Antitumor activity of erlotinib in combination with gemcitabine in in vitro and in vivo models of KRAS-mutated pancreatic cancers ". Oncology Letters 1.2 (2010): 231-235.
Chicago
Furugaki, K., Iwai, T., Kondoh, K., Moriya, Y., Mori, K."Antitumor activity of erlotinib in combination with gemcitabine in in vitro and in vivo models of KRAS-mutated pancreatic cancers ". Oncology Letters 1, no. 2 (2010): 231-235. https://doi.org/10.3892/ol_00000041
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