Role of FOXO3A in trastuzumab combination chemotherapy in esophageal squamous cell carcinoma

Masashi Takahashi; Kazumasa Fukuda; Yoshiro Saikawa; Rieko Nakamura; Norihito Wada; Hirofumi Kawakubo; Hiroya Takeuchi; Yuko Kitagawa

doi:10.21873/anticanres.14147

Role of FOXO3A in trastuzumab combination chemotherapy in esophageal squamous cell carcinoma

Masashi Takahashi, Kazumasa Fukuda, Yoshiro Saikawa, Rieko Nakamura, Norihito Wada, Hirofumi Kawakubo, Hiroya Takeuchi, Yuko Kitagawa

Research output: Contribution to journal › Article › peer-review

1 Citation (Scopus)

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.

Original language	English
Pages (from-to)	1921-1930
Number of pages	10
Journal	Anticancer research
Volume	40
Issue number	4
DOIs	https://doi.org/10.21873/anticanres.14147
Publication status	Published - 2020 Apr

Keywords

Esophageal squamous cell carcinoma
FOXO3A
HER2
Trastuzumab

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.21873/anticanres.14147

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title = "Role of FOXO3A in trastuzumab combination chemotherapy in esophageal squamous cell carcinoma",

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.",

keywords = "Esophageal squamous cell carcinoma, FOXO3A, HER2, Trastuzumab",

author = "Masashi Takahashi and Kazumasa Fukuda and Yoshiro Saikawa and Rieko Nakamura and Norihito Wada and Hirofumi Kawakubo and Hiroya Takeuchi and Yuko Kitagawa",

year = "2020",

month = apr,

doi = "10.21873/anticanres.14147",

language = "English",

volume = "40",

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T1 - Role of FOXO3A in trastuzumab combination chemotherapy in esophageal squamous cell carcinoma

AU - Takahashi, Masashi

AU - Fukuda, Kazumasa

AU - Saikawa, Yoshiro

AU - Nakamura, Rieko

AU - Wada, Norihito

AU - Kawakubo, Hirofumi

AU - Takeuchi, Hiroya

AU - Kitagawa, Yuko

PY - 2020/4

Y1 - 2020/4

N2 - 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.

AB - 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.

KW - Esophageal squamous cell carcinoma

KW - FOXO3A

KW - HER2

KW - Trastuzumab

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Role of FOXO3A in trastuzumab combination chemotherapy in esophageal squamous cell carcinoma

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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