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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. 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.

journal_name

Clin Oral Investig

journal_title

Clinical oral investigations

authors

Hartmann S,Neckel N,Seher A,Mutzbauer G,Brands RC,Linz C,Kübler AC,Müller-Richter UD

doi

10.1007/s00784-015-1566-5

subject

Has Abstract

pub_date

2016-05-01 00:00:00

pages

759-69

issue

4

eissn

1432-6981

issn

1436-3771

pii

10.1007/s00784-015-1566-5

journal_volume

20

pub_type

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