Special Issue on Chemotherapy for Colorectal Cancer: Review ArticleMolecular Markers in the Treatment of Metastatic Colorectal CancerWilson, Peter M. PhD*; LaBonte, Melissa J. PhD*; Lenz, Heinz-Josef MD†Author Information From the *Department of Pathology and †Division of Medical Oncology, University of Southern California/Norris Comprehensive Cancer Center, Keck School of Medicine, Los Angeles, CA. Reprints: Heinz-Josef Lenz, MD, Colorectal Center, GI Oncology, USC/Norris Comprehensive Cancer Center, Keck School of Medicine, 1441 Eastlake Ave, Suite 3456, Los Angeles, CA 90033. E-mail: [email protected]. The Cancer Journal: May 2010 - Volume 16 - Issue 3 - p 262-272 doi: 10.1097/PPO.0b013e3181e07738 Buy Metrics Abstract Although significant progress has been made in colorectal cancer (CRC) treatment within the last decade with the approval of multiple new agents, the prognosis for patients with metastatic CRC remains poor with 5-year survival rates of ∼8%. Resistance to chemotherapy remains a major obstacle in effective CRC treatment and many patients do not receive any clinical benefit from chemotherapy. In addition, other patients will experience adverse reactions to treatment resulting in dose modifications or treatment withdrawal, which can severely reduce treatment efficacy. Currently, significant research efforts are attempting to identify reliable and validated biomarkers with which will guide clinicians to make more informed treatment decisions. Specifically, the use of molecular profiling has the potential to assist the clinician in administering the correct drug, dose, or intervention for the patient before the onset of therapy thereby selecting a treatment strategy likely to have the greatest clinical outcome while minimizing adverse events. However, until recently, personalized medicine is a paradigm that has existed more in conceptual terms than in reality with very few validated biomarkers used routinely in metastatic CRC treatment. Rapid advances in genomic, transcriptomic and proteomic technologies continues to improve our understanding of tumor biology, but the search for reliable biomarkers has turned out to be more challenging than previously anticipated with significant disparity in published literature and limited translation into routine clinical practice. Recent progress with the identification and validation of biomarkers to the anti-epidermal growth factor receptor monoclonal antibodies including KRAS and possibly BRAF provide optimism that the goal of individualized treatment is within reach. This review will highlight and discuss current progress in the search for biomarkers, the challenges this emerging field presents, and the future role of biomarkers in advancing CRC treatment. © 2010 Lippincott Williams & Wilkins, Inc.