Book chapter
The Roswell Park Memorial Institute and Gastrointestinal Tumor Study Group Phase III Experience with the Modulation of 5-Fluorouracil by Leucovorin in Metastatic Colorectal Adenocarcinoma
The Expanding Role of Folates and Fluoropyrimidines in Cancer Chemotherapy, pp.143-155
Advances in Experimental Medicine and Biology, Springer US
04/01/2012
DOI: 10.1007/978-1-4684-5607-3_15
PMID: 3073651
Abstract
The therapeutic activity of 5-Fluorouracil (5-FU) in gastrointestinal (GI) malignancies may be enhanced by increasing the tumor cell reduced folate pools in vivo 1, 2, 3, 4. One of the mechanisms of action of 5-FU is its conversion into fluorodexoyuridylate (FdUMP), which inhibits thymidylate synthetase (TS) 5. FdUMP binds tightly to TS in the presence of the cofactor L-5, 10-methylene tetrahydrofolate (CH2FH4). This interaction of FdUMP and TS leads to the formation of a covalent ternary complex, TS-CH2FH4-FdUMP6. The stability of the ternary complex is maximal when the extracellular folate concentration is 10 umol/L in cell culture7. Therefore, high levels of inhibition of TS and a slow recovery of the enzyme activity can occur only in the presence of sufficient intracellular concentrations of reduced folates.
Details
- Title: Subtitle
- The Roswell Park Memorial Institute and Gastrointestinal Tumor Study Group Phase III Experience with the Modulation of 5-Fluorouracil by Leucovorin in Metastatic Colorectal Adenocarcinoma
- Creators
- Nicholas J. Petrelli - Roswell Park Comprehensive Cancer CenterYoucef M. Rustum - Roswell Park Comprehensive Cancer CenterHoward Bruckner - Icahn School of Medicine at Mount SinaiDonald Stablein - Emmes (United States)
- Resource Type
- Book chapter
- Publication Details
- The Expanding Role of Folates and Fluoropyrimidines in Cancer Chemotherapy, pp.143-155
- Series
- Advances in Experimental Medicine and Biology
- DOI
- 10.1007/978-1-4684-5607-3_15
- PMID
- 3073651
- NLM abbreviation
- Adv Exp Med Biol
- eISSN
- 2214-8019
- ISSN
- 0065-2598
- Publisher
- Springer US; New York, NY
- Language
- English
- Date published
- 04/01/2012
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984359903102771
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