Integrating biomarkers into clinical decision making for colorectal cancer.
The advent of pharmacogenetics and its underlying concept that disparities in drug metabolism, efficacy, and toxicity are determined by the genetic makeup of an individual has birthed the concept and promise of 'tailored medicine.' One such facet of medicine that serves to benefit greatly from this tailored approach is the implementation of chemotherapy in cancer treatment. The past decade has witnessed significant advances in the treatment of colorectal cancer (CRC); however, tumor drug resistance remains a major obstacle in CRC treatment, and many patients do not receive any clinical benefit from chemotherapy. In addition, a significant patient population will experience adverse reactions to treatment, resulting in dose reductions or chemotherapy withdrawal, which can severely affect treatment efficacy. In light of these considerable challenges, significant research efforts are currently under way to identify reliable and validated biomarkers with the power to guide the clinician in deciding when to implement chemotherapy and which strategy is likely to have the greatest clinical impact with minimal toxicities. However, current biomarkers for CRC are few, and the search for reliable biomarkers has turned out to be more challenging than previously anticipated, with much disparity in the published literature. Recent progress in the identification of biomarkers to the anti-epidermal growth factor receptor monoclonal antibodies in the form of KRAS and possibly BRAF provide hope that the goal of individualized treatment is within reach. This review seeks to highlight and discuss current progress in the search for biomarkers, the challenges presented, and the future direction of biomarker-driven CRC treatment.
Wilson
Peter M
PM
Department of Pathology, University of Southern California/Norris Comprehensive Cancer Center, Keck School of Medicine, Los Angeles, CA 90033, USA.
Lenz
Heinz-Josef
HJ
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D003657:Decision Making; D006801:Humans; D058990:Molecular Targeted Therapy; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors*
D009363:Neoplasm Proteins