Stefan Hartmann1, Norbert Neckel2, Axel Seher2, Grit Mutzbauer3, Roman C Brands2, Christian Linz2, Alexander C Kübler2, Urs D A Müller-Richter2. 1. Department of Oral and Maxillofacial Plastic Surgery, University Hospital Würzburg, Pleicherwall 2, 97070, Würzburg, Germany. hartmann_s2@ukw.de. 2. Department of Oral and Maxillofacial Plastic Surgery, University Hospital Würzburg, Pleicherwall 2, 97070, Würzburg, Germany. 3. Institute of Pathology, University Würzburg, Josef-Schneider-Straße 2, 97080, Würzburg, Germany.
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. MATERIALS AND 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. CLINICAL RELEVANCE: Erlotinib and gefitinib show good response in EGF-independent cell lines and might be useful drugs in tumors that are less responsive to cetuximab.
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. MATERIALS AND 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. CLINICAL RELEVANCE: 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: S Hartmann; U Kriegebaum; N Küchler; R C Brands; C Linz; A C Kübler; U D A Müller-Richter Journal: Clin Oral Investig Date: 2013-02-21 Impact factor: 3.573
Authors: J Baselga; D Pfister; M R Cooper; R Cohen; B Burtness; M Bos; G D'Andrea; A Seidman; L Norton; K Gunnett; J Falcey; V Anderson; H Waksal; J Mendelsohn Journal: J Clin Oncol Date: 2000-02 Impact factor: 44.544
Authors: M Maurizi; G Scambia; P Benedetti Panici; G Ferrandina; G Almadori; G Paludetti; R De Vincenzo; M Distefano; D Brinchi; G Cadoni Journal: Int J Cancer Date: 1992-12-02 Impact factor: 7.396