Biomarker Validation Study: Genes Involved In Ubiquitin Proteasome System (Ups) Dependent Egfr-Degradation For Prediction Of Efficacy In Metastatic Colorectal Cancer Patients Treated With Cetuximab.

3571 Background: Epidermal growth factor receptor (EGFR) turnover is a highly regulated process controlling the amount of receptor proteins available for antibody binding. The ubiquitin proteasome system (UPS) is responsible for EGFR degradation. The single nucleotide polymorphism (SNP) rs895374 is located in UbcH7, an E2 ligase conducting neddylation of HECT E3 ligases involved in EGFR degradation. Neddylation activates E3 ligases and switches the balance between degradation and recycling towards degradation. We have previously reported that rs895374 correlates with progression free survival (PFS) in patients (n=108) treated with cetuximab in two phase II studies of further-line treatment. The aim of this study was to validate the predictive value of rs895374 in an independent cohort of cetuximab treated patients with a cetuximab-free chemotherapy arm serving as negative control. Methods: Genomic DNA was isolated from tissue samples of 455 patients (median age 64 years, male 64.2%) treated in first-line ...