SJR: 0.946 SNIP: 0.503 CiteScore™: 2
ISSN Print: 0893-9675
Volumes:Volume 23, 2018 Volume 22, 2017 Volume 21, 2016 Volume 20, 2015 Volume 19, 2014 Volume 18, 2013 Volume 17, 2012 Volume 16, 2011 Volume 15, 2009 Volume 14, 2008 Volume 13, 2007 Volume 12, 2006 Volume 11, 2000 Volume 9, 1998 Volume 8, 1997 Volume 7, 1996 Volume 6, 1995 Volume 5, 1994
Critical Reviews™ in Oncogenesis
Methyl-Group Metabolism and the Response of Colorectal Cancer to 5-Fluorouracil
School of Surgery and Pathology, University of Western Australia, Nedlands 6009, Australia
The major mechanism of action of 5-fluorouracil (5FU)-based therapies is thought to be inhibition of thymidylate synthase (TS). This enzyme catalyzes synthesis of the thymidine nucleotide precursor using a methyl group provided by a folate cofactor. In addition to TS activity levels, various elements of methyl-group metabolism could also be predictive for the response of colorectal cancer (CRC) to 5FU. These include the activity of enzymes involved in folate metabolism, the concentrations of intracellular folate intermediates, and surrogate markers of aberrant methyl-group metabolism, such as DNA methylation and microsatellite instability. The factors of age, gender, common genetic variants, and diet have been shown to influence both systemic and tumor methyl-group metabolism. This has important implications for the prediction of toxicity and response to 5FU, respectively. Identification of predictive factors within the methyl-group metabolism pathway should assist in targeting 5FU treatment to the most responsive CRC patient groups. This is particularly important for early-stage disease where conclusive demonstration of a survival benefit from 5FU in the overall CRC group has thus far proven difficult.
|Begell Digital Portal||Begell Digital Library||eBooks||Journals||References & Proceedings||Research Collections|