Document Detail


Lapatinib inhibits receptor phosphorylation and cell growth and enhances antibody dependent cellular cytoxicity (ADCC) of EGFR and HER2 over-expressing esophageal cancer cell lines.
MedLine Citation:
PMID:  21207425     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Lapatinib is a dual tyrosine kinase inhibitor of the EGFR and HER2 tyrosine kinase domains. EGFR is expressed on 33.3 % and HER2 on 30.3% of esophageal squamous cell carcinomas (ESCC). To explore the potential utility of Lapatinib for therapy of ESCC patients, we evaluated the effect of Lapatinib on a panel of ESCC cell lines. EGFR and HER2 expression by the cell lines was established and the effects of Lapatinib on inhibition of the phosphorylation of HER2, anti-proliferative effect, apoptosis-inducing activity and accumulation of HER2 and EGFR on cell surface was evaluated. Additionally, the combined effect of Lapatinib together with Herceptin or Cetuximab on cell-mediated cytotoxicity was evaluated. Lapatinib inhibited HER2 phosphorylation in HER2 over-expressing, HER2 gene amplification positive ESCC cell line. Lapatinib also inhibited cell proliferation, induced apoptosis, and caused the surface accumulation of HER2 and EGFR in ESCC cell lines. Addition of Lapatinib increased cell-mediated cytotoxicity by 15-25% with 3 ESCC target cell lines. Similarly, Cetuximab-mediated ADCC also increased by 15-30% in 2 ESCC cell lines on addition of Lapatinib. Cumulatively, the data indicate that Lapatinib has activity in EGFR and/or HER2 expressing ESCC cells and the combination therapy of Lapatinib and Cetuximab / Herceptin is a promising strategy in ESCC.
Authors:
Kousaku Mimura; Koji Kono; Takanori Maruyama; Mitsuaki Watanabe; Shinichiro Izawa; Shugo Shiba; Yoshiki Mizukami; Yoshihiko Kawaguchi; Masayuki Inoue; Tetsuo Kono; Aniruddha Choudhury; Rolf Kiessling; Hideki Fujii
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-1-4
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  -     ISSN:  1097-0215     ISO Abbreviation:  -     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-1-5     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
First Department of Surgery, University of Yamanashi, Yamanashi, JAPAN.
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