Pharmacogenomics of 5-Fluorouracil/Oxaliplatin in Colorectal Cancer

Michael   A.   Gordon; Wu      Zhang; Heinz-Josef      Lenz

doi:10.2174/157016006778992741

Abstract

Pharmacogenomic studies in the field of colorectal cancer have recently emerged as tools to benefit patients in receiving tailored chemotherapy and potentially improved therapeutic benefit. 5-fluorouracil/oxalplatin combination che-motherapy has been approved in the United States and Europe for the treatment of advanced colorectal cancer. However, overall efficacy may be compromised by dose-limiting toxicity and varying inter-individual responses to treatment. De-termining who is most likely to benefit from 5-FU/oxaliplatin is of great importance, and may be determined in part by pharmacogenomic studies. Genes involved in the cytotoxic and metabolic pathways of 5FU and oxaliplatin may be pre-dictive and prognostic markers for colorectal cancer. Examining polymorphic variants leading to altered function of these relevant genes offers an approach to further individualize chemotherapeutic treatment. A number of studies have impli-cated significant genes in altered clinical outcome, indicating the need f or an established comprehensive genetic profile to predict efficacy of 5-FU/oxaliplatin. In addition to polymorphic studies, array-based technology has recently emerged as a tool to examine global gene expression in predicting outcome to chemotherapy. The ultimate goal of pharmacogenomic studies in colorectal cancer is to develop a genetic profile to tailor chemotherapeutics to the individual patient. With an in-creased knowledge of why patients have altered responses to 5-FU/oxaliplatin, there can be greater accuracy in selecting the most appropriate therapy.

Keywords: 5-FU therapy, TYMS polymorphisms, dihydropyrimidine dehydrogenase, glutathione S-transferase, microarray

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