5-Fluorouracil: mechanisms of action and clinical strategies

Abstract

The fluoropyrimidine 5-fluorouracil (5-FU) is an antimetabolite drug that is widely used for the treatment of cancer, particularly for colorectal cancer. 5-FU exerts its anticancer effects through inhibition of thymidylate synthase (TS) and incorporation of its metabolites into RNA and DNA. Modulation strategies, such as co-treatment with leucovorin and methotrexate, have been developed to increase the anticancer activity of 5-FU. Molecular biomarkers that predict tumour sensitivity to 5-FU have been identified, including mRNA and protein expression levels of TS. DNA microarray analysis of 5-FU-responsive genes will greatly facilitate the identification of new biomarkers, novel therapeutic targets and the development of rational drug combinations.