Individualization of therapy for colorectal cancer based on clinical and molecular parameters.
To improve the treatment of patients with colorectal cancer, efforts must be directed toward the identification of patients likely to respond to a specific therapy, those who will experience severe toxicities, and those who will benefit from chemotherapy in the adjuvant setting. In recent years, studies on a global scale have attempted to define subsets of biochemical markers that may predict response to treatment (evaluated through clinical response, toxicity, and time to disease progression), and prognostic markers, which are equally important in determining how aggressive the disease is (generally evaluated in terms of overall survival), and the likelihood of disease recurrence after surgery. The science of pharmacogenomics is emerging as a useful molecular tool to investigate the disparity in drug efficacy by analyzing variations such as genetic polymorphisms in drug targets, metabolizing enzymes, transporters, and influential receptors. Consequently, the identification of accurate and validated predictive and prognostic markers combined with an increasing arsenal of therapeutic agents will improve the clinician's ability to tailor effective therapy to the molecular profile of the patient while minimizing life-threatening toxicities. This paper describes markers under study in the setting of colorectal cancer, including loss of heterozygosity of 18q and microsatellite instability, polymorphisms in thymidylate synthase, IL-8, CXCR-2, vascular endothelial growth factor, epidermal growth factor and their receptors, and K-ras mutations.
Pohl
Alexandra
A
Division of Medical Oncology, University of Southern California/Norris Comprehensive Cancer Center, Keck School of Medicine, Los Angeles, CA.
Lenz
Heinz-Josef
HJ