Pharmacogenomics in Colorectal Cancer

Several developments in the past few years have incrementally progressed the field and provided additional insights into the management of advanced colorectal cancer. The equivalence of several front-line regimens based on fluorouracil, capecitabine, oxaliplatin, irinotecan, bevacizumab, and cetuximab has provided opportunities for increased tailoring of therapies for individual patients. Nevertheless, some patients may suffer from the adverse drug reactions which will probably be the main cause of chemotherapy failure. The goal of pharmacogenomics is to find correlations between clinical responses to drugs and the genetic profiles of patients. Genes which codify for the metabolism enzymes, receptor proteins, or protein targets of chemotherapy agents often present various genetic polymorphisms. An assay is already commercially available for genotypic testing of the enzyme UGT1A1 which is predictive of toxicity from irinotecan. The advent of high-throughput methodologies, such as microarrays, enables tumor samples to be profiled on a global scale. Genes which may represent molecular signatures of sensitivity to fluorouracil and oxaliplatin has been identified with DNA microarray analysis.