Targeting EGFR and HER-2 with cetuximab- and trastuzumab-mediated immunotherapy in oesophageal squamous cell carcinoma

Br J Cancer. 2007 Aug 20;97(4):494-501. doi: 10.1038/sj.bjc.6603885. Epub 2007 Jul 10.


We previously reported that oesophageal squamous cell carcinoma (SCC) had a relatively high incidence of EGFR and HER-2 overexpression. Thus, anti-HER family targeting may become a promising approach to treat oesophageal SCC. In the present study, we investigated (a) the distribution of EGFR and HER-2 expression in oesophageal SCC (n=66) detected by immunohistochemistry and (b) cetuximab- and/or trastuzumab-mediated biological activity (antiproliferative effect by the MTT assay, apoptosis-inducing activity by the annexin V/propidium iodide assay, and antibody-dependent cellular cytotoxicity (ADCC) by the (51)Cr-release assay) against oesophageal SCC cell lines with various levels of EGFR and HER-2. Twelve of the 66 patients (18%) showed both EGFR- and HER-2 expression. Out of both EGFR- and HER-2-positive cases, nine cases (75%) showed EGFR and HER-2 expression in individually distinct regions. Furthermore, the combination of cetuximab and trastuzumab could induce synergistic antiproliferative effects and additional ADCC activities against not all, but several oesophageal SCC cell lines with EGFR and HER-2 expression. The combination of cetuximab and trastuzumab may be useful in the treatment of oesophageal SCC with EGFR and HER-2 expression.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / therapy*
  • Cell Proliferation / drug effects
  • Cetuximab
  • ErbB Receptors / antagonists & inhibitors*
  • ErbB Receptors / genetics
  • ErbB Receptors / immunology
  • Esophageal Neoplasms / genetics
  • Esophageal Neoplasms / mortality
  • Esophageal Neoplasms / therapy*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunotherapy*
  • Male
  • Middle Aged
  • Receptor, ErbB-2 / antagonists & inhibitors*
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / immunology
  • Survival Analysis
  • Trastuzumab
  • Tumor Cells, Cultured


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • ErbB Receptors
  • Receptor, ErbB-2
  • Trastuzumab
  • Cetuximab