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Clinical Oral Investigations
Published in: Clinical Oral Investigations 4/2016

01-05-2016 | Original Article

Erlotinib and gefitinib responsiveness in head and neck cancer cell lines—a comparing analysis with cetuximab

Authors: Stefan Hartmann, Norbert Neckel, Axel Seher, Grit Mutzbauer, Roman C. Brands, Christian Linz, Alexander C. Kübler, Urs D. A. Müller-Richter

Published in: Clinical Oral Investigations | Issue 4/2016

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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.
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Metadata
Title
Erlotinib and gefitinib responsiveness in head and neck cancer cell lines—a comparing analysis with cetuximab
Authors
Stefan Hartmann
Norbert Neckel
Axel Seher
Grit Mutzbauer
Roman C. Brands
Christian Linz
Alexander C. Kübler
Urs D. A. Müller-Richter
Publication date
01-05-2016
Publisher
Springer Berlin Heidelberg
Published in
Clinical Oral Investigations / Issue 4/2016
Print ISSN: 1432-6981
Electronic ISSN: 1436-3771
DOI
https://doi.org/10.1007/s00784-015-1566-5

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