Cetuximab insufficiently inhibits glioma cell growth due to persistent EGFR downstream signaling

TY - JOUR

T1 - Cetuximab insufficiently inhibits glioma cell growth due to persistent EGFR downstream signaling

AU - Hasselbalch, Benedikte

AU - Lassen, Ulrik

AU - Poulsen, Hans S

AU - Stockhausen, Marie-Thérése

PY - 2010/9

Y1 - 2010/9

N2 - 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.

AB - 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.

U2 - 10.3109/07357907.2010.483506

DO - 10.3109/07357907.2010.483506

M3 - Journal article

SN - 0735-7907

VL - 28

SP - 775

EP - 787

JO - Cancer Investigation

JF - Cancer Investigation

IS - 8

ER -