Influence of epidermal growth factor receptor expression on the cetuximab and panitumumab response rates of head and neck carcinoma cells.
OBJECTIVE
To examine the impact of epidermal growth factor receptor (EGFR) expression level on the efficacy of monoclonal antibodies against the EGFR.


METHODS
In four human head and neck carcinoma cell lines, epidermal growth factor expression was knocked down by lentiviral RNA interference. Next, the efficacies of cetuximab and panitumumab at concentrations of 4, 40, and 400 μg/ml were measured by real time cell analysis for a 48-h duration. Finally, the different response rates to the drugs were statistically analyzed.


RESULTS
The lentiviral EGFR knockdown efficiency ranged from 18 to 54 % across all of the cell lines. All original cell lines exhibited rather poor or inverse responses with regard to EGFR-AB treatment. In contrast, inhibiting EGFR expression in the same cell lines yielded statistically significant better responses to cetuximab or panitumumab treatment.


CONCLUSIONS
The cell lines used in this study responded poorly to cetuximab and panitumumab. Better anti-EGFR treatment efficacy was related to lower EGFR expression in head and neck cancer cell lines. These findings might influence the selection of patients to receive cetuximab and panitumumab treatment for head and neck cancer.
Department of Oral and Maxillofacial Plastic Surgery (Head: A. C. Kübler), University Hospital Würzburg, Pleicherwall 2, 97070 Würzburg, Germany. Electronic address: hartmann_s2@ukw.de.
Stefan
S
Hartmann
Department of Oral and Maxillofacial Plastic Surgery (Head: A. C. Kübler), University Hospital Würzburg, Pleicherwall 2, 97070 Würzburg, Germany.
Axel
A
Seher
Department of Oral and Maxillofacial Plastic Surgery (Head: A. C. Kübler), University Hospital Würzburg, Pleicherwall 2, 97070 Würzburg, Germany.
Roman C
RC
Brands
Department of Oral and Maxillofacial Plastic Surgery (Head: A. C. Kübler), University Hospital Würzburg, Pleicherwall 2, 97070 Würzburg, Germany.
Christian
C
Linz
Institute of Pathology (Head: A. Rosenwald), University Würzburg, Josef-Schneider-Straße 2, 97080 Würzburg, Germany.
Grit
G
Lessner
Department of Oral and Maxillofacial Plastic Surgery (Head: A. C. Kübler), University Hospital Würzburg, Pleicherwall 2, 97070 Würzburg, Germany.
Hartmut
H
Böhm
Department of Oral and Maxillofacial Plastic Surgery (Head: A. C. Kübler), University Hospital Würzburg, Pleicherwall 2, 97070 Würzburg, Germany.
Alexander C
AC
Kübler
Department of Oral and Maxillofacial Plastic Surgery (Head: A. C. Kübler), University Hospital Würzburg, Pleicherwall 2, 97070 Würzburg, Germany.
Urs D A
UD
Müller-Richter
D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002277:Carcinoma / Q000188:drug therapy / Q000473:pathology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000473:pathology; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D000068818:Cetuximab / Q000494:pharmacology* / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000187:drug effects*; D005434:Flow Cytometry / Q000379:methods; D055785:Gene Knockdown Techniques; D005822:Genetic Vectors / Q000235:genetics; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000473:pathology*; D006801:Humans; D007822:Laryngeal Neoplasms / Q000188:drug therapy / Q000473:pathology; D016086:Lentivirus / Q000235:genetics; D009062:Mouth Neoplasms / Q000188:drug therapy / Q000473:pathology; D000077544:Panitumumab; D034622:RNA Interference; D034741:RNA, Small Interfering; D014062:Tongue Neoplasms / Q000188:drug therapy / Q000473:pathology
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D034741:RNA, Small Interfering; D000077544:Panitumumab; D066246:ErbB Receptors; D000068818:Cetuximab
Cetuximab; EGFR; HNSCC; Knockdown; Panitumumab