Lapatinib inhibits the growth of esophageal squamous cell carcinoma and synergistically interacts with 5-fluorouracil in patient-derived xenograft models

Hou,Wenmin; Qin,Xia; Zhu,Xuehua; Fei,Maogui; Liu,Ping; Liu,Li; Moon,Hanlim; Zhang,Pingkuan; Greshock,Joel; Bachman,Kurtis  E.; Ye,Bang-Ce; Wang,Hui; Zang,Crystal  Ying Qin

doi:10.3892/or.2013.2500

Lapatinib inhibits the growth of esophageal squamous cell carcinoma and synergistically interacts with 5-fluorouracil in patient-derived xenograft models

Authors:
- Wenmin Hou
- Xia Qin
- Xuehua Zhu
- Maogui Fei
- Ping Liu
- Li Liu
- Hanlim Moon
- Pingkuan Zhang
- Joel Greshock
- Kurtis E. Bachman
- Bang-Ce Ye
- Hui Wang
- Crystal Ying Qin Zang
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Affiliations: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai 200031, P.R. China, Cancer Research, GlaxoSmithKline R&D Center, Shanghai 201203, P.R. China, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, Shanghai 200092, P.R. China, Cancer Research, GlaxoSmithKline, Collegeville, PA 19426, USA, Oncology Medicine, GlaxoSmithKline R&D Center, Shanghai 201203, P.R. China, Laboratory of Biosystems and Microanalysis, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, P.R. China
Published online on: May 27, 2013 https://doi.org/10.3892/or.2013.2500
Pages: 707-714

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Abstract

Lapatinib is a dual tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR) and human EGFR-2 (HER2) tyrosine kinase domains. To explore the potential utility of lapatinib for the treatment of esophageal squamous cell carcinoma (ESCC), we examined the expression profiles of EGFR and HER2 in tumor tissues and in paired adjacent non-neoplastic tissues from patients with ESCC. We evaluated the antitumor effects of lapatinib alone or in combination with oxaliplatin or 5-fluorouracil (5-FU) on a panel of primary ESCC cells in vitro with various levels of EGFR and HER2 expression. The in vivo effect of lapatinib alone or in combination with oxaliplatin or 5-FU was evaluated using a primary ESCC xenograft model. EGFR was overexpressed in 80.9% (76/94) of the ESCC samples, while 24.5% (23/94) of the samples overexpressed HER2. EGFR and HER2 co-overexpression was detected in 22.3% of samples (21/94). In vitro, the primary ESCC cells were more sensitive to lapatinib combined with 5-FU or oxaliplatin than to lapatinib alone. Lapatinib in combination with 5-FU had more potent antitumor effects in the primary ESCC xenograft model, and markedly reduced the phosphorylation of EGFR and HER2, compared with lapatinib alone or in combination with oxaliplatin. These data indicate that lapatinib has activity in EGFR- and/or HER2-expressing ESCC primary cells, and that lapatinib in combination with 5-FU may be a promising treatment strategy for patients with ESCC.

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