title: The effect of monoclonal antibody cetuximab (C225) in combination with tyrosine kinase inhibitor gefitinib (ZD1839) on colon cancer cell lines.
abstract: OBJECTIVE
  The epidermal growth factor receptor (EGFR) is abnormally activated in many tumours. Two different categories of compounds targeting EGFR, monoclonal antibodies (mAbs) and low molecular weight tyrosine kinase inhibitors (TKIs), which target extracellular and intracellular domains of the receptor, respectively, have shown antitumour activity. We decided to explore whether the combined administration of cetuximab, a mAb, and gefitinib, a TKI, had superior antitumour activity than either agent given alone.
  
  
  METHODS
  We studied the effects of cetuximab alone, gefitinib alone and the combination of cetuximab and gefitinib in two colon cancer cell lines, HT-29 and LoVo. The effects of these two agents on cell proliferation and induction of apoptosis were evaluated.
  
  
  RESULTS
  Dose-dependent activity of cetuximab alone or gefitinib alone or the combination was observed for both colon cancer cell lines. In addition, the combined treatment with cetuximab and gefitinib resulted in a synergistic and more pronounced growth effect on cell proliferation and induction of apoptosis than either single-agent treatment.
  
  
  CONCLUSIONS
  Our findings suggest that combined treatment with distinct EGFR inhibitory agents can augment the antitumour response over that realised with a single EGFR inhibitor. New and tempting treatment strategies on the EGFR target consisting of a double hit with a mAb and a TKI may improve the therapeutic ratio for colorectal cancer in future clinical trials.
authors.affiliation: Department of Gastrointestinal Oncology, The Third Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Heng-Heng
authors.initials: HH
authors.lastname: Yuan
authors.forename: Yu
authors.initials: Y
authors.lastname: Han
authors.forename: Wei-xin
authors.initials: WX
authors.lastname: Bian
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.forename: Yu-xian
authors.initials: YX
authors.lastname: Bai
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D000068818:Cetuximab; D003110:Colonic Neoplasms / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D000077156:Gefitinib; D006801:Humans; D011799:Quinazolines / Q000494:pharmacology*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D011799:Quinazolines; D066246:ErbB Receptors; D000068818:Cetuximab; D000077156:Gefitinib