Cetuximab Insufficiently Inhibits Glioma Cell Growth Due to Persistent EGFR Downstream Signaling

ABSTRACT

Overexpression and/or amplification of the epidermal growth factor receptor (EGFR) is present in 35–45% of primary glioblastoma multiforme tumors and has been correlated with a poor prognosis. In this study, we investigated the effect of cetuximab and intracellular signaling pathways downstream of EGFR, important for cell survival and proliferation. We show insufficient EGFR downregulation and competition with endogenous EGFR ligands upon cetuximab treatment. Dose–response experiments showed inhibition of EGFR phosphorylation without affecting two of the prominent downstream signaling pathways. Our results indicate that amplification and/or overexpression of EGFR is an unsatisfactory predictor for response to cetuximab.

Keywords: :

• EGFR
• Cetuximab
• Glioma
• Glioblastoma multiforme
• PTEN

ACKNOWLEDGMENTS

This study was supported by Ministry of Health and Prevention (journal number 2006-12103-254) and an unrestricted research grant from E. Merck AB, (Stockholm, Sweden) and Roche A/S (Hvidovre, Denmark). These companies were not involved in either interpretation of the results of this study or presentation of data.

Declaration of interest: The authors report no conflict of interest. The authors alone are responsible for the content and writing of this paper.