B18
Using a mouse model of colon cancer in the search for a genetic signature of response to anti epidermal growth factor receptor therapy
Paul Shaw, Tim Maughan, Alan Clarke
Cardiff University, Cardiff, UK
Being able to reliably predict patients most likely to respond to novel cancer therapies is a worthwhile goal. Although it is now evident that colorectal cancer response to monoclonal antibodies (cetuximab and panitumumab) against the Epidermal Growth Factor Receptor is determined by tumour KRAS mutation status, further research is still warranted. Translational research using the Apcmin/+ mouse to discover gene expression changes in intestinal polyps in response to the small molecular tyrosine kinase inhibitor against EGFR (Iressa) are to be compared to gene changes in human rectal cancer biopsies from patients exposed to neoadjuvant cetuximab. Time course analysis of microarray data from murine tissue exposed to anti-EGFR therapy (0-24 hours) has revealed dysregulated genes of potential biological significance in colon cancer. Validation using Real Time PCR of technical and biological replicates is underway. The latter will also include the use of tissue exposed to a recently available monoclonal antibody against murine EGFR. Similarly identified genes of interest secondary to anti-EGFR therapy in mouse and man may point ultimately to a signature of response which can be tested in future clinical trials as a predictive biomarker of response. Furthermore the genetic signature obtained has the potential to increase our knowledge of EGFR biology (including resistance mechanisms and unknown mechanisms of action) and may help identify new therapeutic targets.
