Treatment of HNSCC cell lines with the EGFR-specific inhibitor cetuximab (Erbitux) results in paradox phosphorylation of tyrosine 1173 in the receptor.
Overexpression of the epidermal growth factor receptor (EGFR, ErbB1, HER1) is frequent in head and neck squamous cell carcinomas (HNSCCs) and correlates with disease progression. Inhibition of EGFR with the kinase inhibitor AG1478 abolished receptor phosphorylation and reduced cell proliferation. However, treatment of HNSCC cells with cetuximab (Erbitux), a monoclonal antibody designed to block the EGFR ligand binding site, led to paradox EGFR activation due to hyperphosphorylation of tyrosine 1173, however, with a concomitant reduction in Erk1/2 phosphorylation levels. No pronounced influence on cell proliferation levels could be observed after treatment with this antibody. Since cetuximab appears able to activate EGFR in HNSCC cell lines, it is necessary to rethink the exact mechanisms by which cetuximab that recently was approved for the treatment of advanced head and neck cancer, inhibits tumor growth.
Mandic
Robert
R
Department of Otolaryngology, Head and Neck Surgery, Philipps University Marburg, Deutschhausstrasse 3, D-35037 Marburg, Germany. mandic@med.uni-marburg.de
Rodgarkia-Dara
Chantal J
CJ
Zhu
Li
L
Folz
Benedikt J
BJ
Bette
Michael
M
Weihe
Eberhard
E
Neubauer
Andreas
A
Werner
Jochen A
JA
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000378:metabolism / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000473:pathology; D002453:Cell Cycle / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival; D000068818:Cetuximab; D002945:Cisplatin / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D010766:Phosphorylation; D011799:Quinazolines; D014443:Tyrosine / Q000378:metabolism*; D020032:Tyrphostins / Q000378:metabolism
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D011799:Quinazolines; D020032:Tyrphostins; C101044:RTKI cpd; D014443:Tyrosine; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D048049:Extracellular Signal-Regulated MAP Kinases; D000068818:Cetuximab; D002945:Cisplatin