title: Erlotinib and gefitinib responsiveness in head and neck cancer cell lines--a comparing analysis with cetuximab.
abstract: OBJECTIVE
  The objective of this study is to examine the efficacy of erlotinib and gefitinib with respect to epidermal growth factor (EGF) and cetuximab response in head and neck cancer cell lines.
  
  
  METHODS
  Five human head and neck carcinoma cell lines were treated with EGF, cetuximab, erlotinib, and gefitinib, and the effects were measured with a crystal violet assay. The efficacies of cetuximab, erlotinib, and gefitinib in clinically relevant concentrations were statistically analyzed. The expression of the epidermal growth factor receptor (EGFR) and phosphorylation patterns were detected with fluorescence-activated cell sorting (FACS) analysis and western blot analysis. The endogenous production of EGF by the cells was detected with an enzyme-linked immunosorbent assay. Finally, EGFR, KRAS, BRAF, and PI3K mutation analyses were performed.
  
  
  RESULTS
  All of the cell lines had a poor or no response to EGF but exhibited distinct EGFR phosphorylation and EGFR expression. Compared to cetuximab, erlotinib and gefitinib demonstrated a greater impact on the majority of the cell lines. The only cell line that showed a concentration-dependent behavior toward EGF and strong EGFR phosphorylation was entirely resistant to cetuximab, erlotinib, and gefitinib. The production of EGF in all cell lines was very low. Mutational analysis of all cell lines revealed wild-type EGFR, KRAS, BRAF, and PI3K.
  
  
  CONCLUSIONS
  The prediction of anti-EGFR treatment cannot be based on responsiveness to EGF or EGFR activation.
  
  
  CONCLUSIONS
  Erlotinib and gefitinib show good response in EGF-independent cell lines and might be useful drugs in tumors that are less responsive to cetuximab.
authors: Department of Oral and Maxillofacial Plastic Surgery, University Hospital Würzburg, Pleicherwall 2, 97070, Würzburg, Germany. hartmann_s2@ukw.de.
authors: Stefan
authors: S
authors: Hartmann
authors: Department of Oral and Maxillofacial Plastic Surgery, University Hospital Würzburg, Pleicherwall 2, 97070, Würzburg, Germany.
authors: Norbert
authors: N
authors: Neckel
authors: Department of Oral and Maxillofacial Plastic Surgery, University Hospital Würzburg, Pleicherwall 2, 97070, Würzburg, Germany.
authors: Axel
authors: A
authors: Seher
authors: Institute of Pathology, University Würzburg, Josef-Schneider-Straße 2, 97080, Würzburg, Germany.
authors: Grit
authors: G
authors: Mutzbauer
authors: Department of Oral and Maxillofacial Plastic Surgery, University Hospital Würzburg, Pleicherwall 2, 97070, Würzburg, Germany.
authors: Roman C
authors: RC
authors: Brands
authors: Department of Oral and Maxillofacial Plastic Surgery, University Hospital Würzburg, Pleicherwall 2, 97070, Würzburg, Germany.
authors: Christian
authors: C
authors: Linz
authors: Department of Oral and Maxillofacial Plastic Surgery, University Hospital Würzburg, Pleicherwall 2, 97070, Würzburg, Germany.
authors: Alexander C
authors: AC
authors: Kübler
authors: Department of Oral and Maxillofacial Plastic Surgery, University Hospital Würzburg, Pleicherwall 2, 97070, Würzburg, Germany.
authors: Urs D A
authors: UD
authors: Müller-Richter
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D045744:Cell Line, Tumor; D000068818:Cetuximab / Q000494:pharmacology*; D000069347:Erlotinib Hydrochloride / Q000494:pharmacology*; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000069347:Erlotinib Hydrochloride; D019869:Phosphatidylinositol 3-Kinases; D000068818:Cetuximab
keywords: Cetuximab; EGFR; Erlotinib; Gefitinib; HNSCC