Secondary Resistance to Anti-EGFR Therapy by Transcriptional Reprogramming in Patient-Derived Colorectal Cancer Models

Global mRNA expression profiling of patient derived colon cancer xenograft models (N=10) showing disease control under cetuximab treatment were collected using Agilent human whole genome array (G4845A AMADID 026652, cRNA 4x44k V2) . All xenograft models were wildtype for KRAS, NRAS, BRAF and PIK3CA. All Mice were treated with cetuximab (Merck Serono) by intra peritoneal (i.p.) injection twice per week and dosed at 25mg/kg to establish response characteristics. Tumors were chronically treated to establish cetuximab secondary resistant tumors . Three conditions (untreated control (K) vs 5 days cetuximab treatment (5dC) while pdx tumors were responsive to cetuximab vs secondary resistant tumors (C) following chronic cetuximab treatment) were analyzed. Untreated control tumors are represented by two to four biological replicates, 5 days cetuximab treated tumors by 3-4 biological replicates. For cetuximab secondary resistant tumors, cases with only one secondary resistant tumor are represented by 3 technical replicates, cases with >1 secondary resistant tumors, each is (with the exception of one tumor) represented by two technical replicates or by biological replicates > 4.