Role of FOXO3A in Trastuzumab Combination Chemotherapy in Esophageal Squamous Cell Carcinoma
Masashi Takahashi1, Kazumasa Fukuda2, Yoshiro Saikawa1
1Department of Surgery, School of Medicine, Keio University, Tokyo, Japan.
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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