Abstract | PURPOSE: EXPERIMENTAL DESIGN: Thirty-three HNSCC tumors were evaluated by immunostaining and reverse transcription-PCR for EGFRvIII expression. A representative HNSCC cell line was stably transfected with an EGFRvIII expression construct. EGFRvIII-expressing cells and vector-transfected controls were compared for growth rates in vitro and in vivo as well as chemotherapy-induced apoptosis and the consequences of EGFR inhibition using the chimeric monoclonal antibody C225/ cetuximab/ Erbitux. RESULTS:
EGFRvIII expression was detected in 42% of HNSCC tumors where EGFRvIII was always found in conjunction with wild-type EGFR. HNSCC cells expressing EGFRvIII showed increased proliferation in vitro and increased tumor volumes in vivo compared with vector-transfected controls. Furthermore, EGFRvIII-transfected HNSCC cells showed decreased apoptosis in response to cisplatin and decreased growth inhibition following treatment with C225 compared with vector-transfected control cells. CONCLUSIONS:
EGFRvIII is expressed in HNSCC where it contributes to enhanced growth and resistance to targeting wild-type EGFR. The antitumor efficacy of EGFR targeting strategies may be enhanced by the addition of EGFRvIII-specific blockade.
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Authors | John C Sok, Francesca M Coppelli, Sufi M Thomas, Miriam N Lango, Sichuan Xi, Jennifer L Hunt, Maria L Freilino, Michael W Graner, Carol J Wikstrand, Darell D Bigner, William E Gooding, Frank B Furnari, Jennifer R Grandis |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 12
Issue 17
Pg. 5064-73
(Sep 01 2006)
ISSN: 1078-0432 [Print] United States |
PMID | 16951222
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Antibodies, Monoclonal
- epidermal growth factor receptor VIII
- ErbB Receptors
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Topics |
- Adult
- Aged
- Aged, 80 and over
- Animals
- Antibodies, Monoclonal
(pharmacology)
- Antineoplastic Combined Chemotherapy Protocols
(therapeutic use)
- Carcinoma, Squamous Cell
(drug therapy, genetics, pathology)
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Drug Resistance, Neoplasm
- ErbB Receptors
(antagonists & inhibitors, genetics)
- Female
- Gene Expression Profiling
- Head and Neck Neoplasms
(drug therapy, genetics, pathology)
- Humans
- Male
- Mice
- Mice, Nude
- Middle Aged
- Mutation
- Neoplasm Transplantation
- Reverse Transcriptase Polymerase Chain Reaction
(methods)
- Transplantation, Heterologous
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