Pharmacogenetic influences on treatment response and toxicity in colorectal cancer

Current use of chemotherapeutic and targeted agents for advanced colorectal cancer (CRC) results in high tumor response rates and relatively long overall patient survival. Fluoropyrimidines, irinotecan, and oxaliplatin are highly active in first-line and salvage therapy of colorectal cancer. Targeted therapies, including anti-angiogenesis agents and anti-epidermal growth factor receptor antibodies, have been incorporated with traditional chemotherapy and offer additional options for patients with CRC. However, there is marked variability in response to therapy, as well as frequency and severity of toxicities. Molecular markers and pharmacogenomic profiling may improve prediction of patients who will experience significant benefit or toxicity from currently available agents. Validation of these predictive factors in prospective clinical trials is now necessary to allow for a rational and systematic individualization of cancer therapy.