Project description:Expression analysis (RNA-seq) and RPPA data (see publication) of head and neck cancer patient-derived xenographs (PDXs) revealed Sox-2 and Cav-1 expression to be biomarker determinants of head and neck cancer patient tumor response to cetuximab (EGFR inhibitor) treatment.
Project description:Head and neck cancer is a hetergeneous disease. Based on previoulsy defined molecular subtypes we associated gene expression with response to different compounds. We used microarry gene expression for molecular subtyping Cetuximab is the single targeted therapy approved for the treatment of head and neck cancer (SCCHN). Predictive biomarkers have not been established in the clinical setting and patient stratification based on molecular tumor profiles has not been possible. Since EGFR pathway activation is pronounced in basal subtype, we hypothesized this activation could be a predictive signature for an EGFR directed treatment. From our patient derived xenograft platform of head and neck cancer, 28 models were subjected to Affymetrix gene expression studies on HG U133+ 2.0. Based on the expression of 821 genes, the subtype of each of the 28 models was determined by integrating gene expression profiles through centroid-clustering with previously published gene expression data by Keck et al.,CCR 2015. Response was evaluated by comparing tumor volume at treatment initiation and after three weeks of treatment (RTV).
