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Role of FOXO3A in Trastuzumab Combination Chemotherapy in Esophageal Squamous Cell Carcinoma.
Takahashi, Masashi; Fukuda, Kazumasa; Saikawa, Yoshiro; Nakamura, Rieko; Wada, Norihito; Kawakubo, Hirofumi; Takeuchi, Hiroya; Kitagawa, Yuko.
Affiliation
  • Takahashi M; Department of Surgery, School of Medicine, Keio University, Tokyo, Japan.
  • Fukuda K; Department of Surgery, School of Medicine, Keio University, Tokyo, Japan fukudak@z6.keio.jp.
  • Saikawa Y; Department of Surgery, School of Medicine, Keio University, Tokyo, Japan.
  • Nakamura R; Department of Surgery, School of Medicine, Keio University, Tokyo, Japan.
  • Wada N; Department of Surgery, School of Medicine, Keio University, Tokyo, Japan.
  • Kawakubo H; Department of Surgery, School of Medicine, Keio University, Tokyo, Japan.
  • Takeuchi H; Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan.
  • Kitagawa Y; Department of Surgery, School of Medicine, Keio University, Tokyo, Japan.
Anticancer Res ; 40(4): 1921-1930, 2020 Apr.
Article in En | MEDLINE | ID: mdl-32234881
ABSTRACT
BACKGROUND/

AIM:

Targeting of the human epidermal growth factor receptor 2 (HER2) is suggested to be beneficial for esophageal squamous cell carcinoma (ESCC) patients with HER2 amplification. In this study, we evaluated the effects of combination chemotherapy with HER2-targeted drug trastuzumab in ESCC cells and examined the underlying mechanism contributing to these effects. MATERIALS AND

METHODS:

HER2 expression was verified, and the efficacy of chemotherapy with and without trastuzumab was investigated in vitro and in vivo.

RESULTS:

The combination of trastuzumab and a combined-modality therapy stimulated the PI3K/Akt pathway in ESCC cells overexpressing HER2. Trastuzumab treatment resulted in the intranuclear accumulation of FOXO3A in ESCC xenografts overexpressing HER2. The combination of trastuzumab and a combined-modality therapy enhanced antitumor effects in HER2-overexpressing ESCC xenografts.

CONCLUSION:

FOXO3A plays an important role in mediating the effects of trastuzumab, and combination chemotherapy may be a promising treatment for patients with HER2-overexpressing ESCC.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Receptor, ErbB-2 / Trastuzumab / Forkhead Box Protein O3 / Esophageal Squamous Cell Carcinoma Limits: Animals / Humans Language: En Journal: Anticancer Res Year: 2020 Document type: Article Affiliation country: Japan
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Receptor, ErbB-2 / Trastuzumab / Forkhead Box Protein O3 / Esophageal Squamous Cell Carcinoma Limits: Animals / Humans Language: En Journal: Anticancer Res Year: 2020 Document type: Article Affiliation country: Japan