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Title: Molecular Response to Cetuximab and Efficacy of Preoperative Cetuximab-Based Chemoradiation in Rectal Cancer
Authors: Debucquoy, Annelies ×
Haustermans, Karin
Daemen, Anneleen
Aydin, Selda
Libbrecht, Louis
Gevaert, Olivier
De Moor, Bart
Tejpar, Sabine
McBride, William H
Penninckx, Freddy
Scalliet, Pierre
Stroh, Christopher
Vlassak, Soetkin
Sempoux, Christine
Machiels, Jean-Pascal #
Issue Date: Jun-2009
Publisher: Grune & Stratton
Series Title: Journal of Clinical Oncology vol:27 issue:17 pages:2751-2757
Abstract: PURPOSE: To characterize the molecular pathways activated or inhibited by cetuximab when combined with chemoradiotherapy (CRT) in rectal cancer and to identify molecular profiles and biomarkers that might improve patient selection for such treatments. PATIENTS AND METHODS: Forty-one patients with rectal cancer (T3-4 and/or N+) received preoperative radiotherapy (1.8 Gy, 5 days/wk, 45 Gy) in combination with capecitabine and cetuximab (400 mg/m(2) as initial dose 1 week before CRT followed by 250 mg/m(2)/wk for 5 weeks). Biopsies and plasma samples were taken before treatment, after cetuximab but before CRT, and at the time of surgery. Proteomics and microarrays were used to monitor the molecular response to cetuximab and to identify profiles and biomarkers to predict treatment efficacy. RESULTS: Cetuximab on its own downregulated genes involved in proliferation and invasion and upregulated inflammatory gene expression, with 16 genes being significantly influenced in microarray analysis. The decrease in proliferation was confirmed by immunohistochemistry for Ki67 (P = .01) and was accompanied by an increase in transforming growth factor-alpha in plasma samples (P < .001). Disease-free survival (DFS) was better in patients if epidermal growth factor receptor expression was upregulated in the tumor after the initial cetuximab dose (P = .02) and when fibro-inflammatory changes were present in the surgical specimen (P = .03). Microarray and proteomic profiles were predictive of DFS. CONCLUSION: Our study showed that a single dose of cetuximab has a significant impact on the expression of genes involved in tumor proliferation and inflammation. We identified potential biomarkers that might predict response to cetuximab-based CRT.
URI: 
ISSN: 0732-183X
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Experimental Radiotherapy
ESAT - STADIUS, Stadius Centre for Dynamical Systems, Signal Processing and Data Analytics
Hepatology
Abdominal Surgical Oncology
Molecular Digestive Oncology (+)
× corresponding author
# (joint) last author

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