Fluoropyrimidine activity (Homo sapiens)
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Description
The main mechanism of 5-FU activation is conversion to fluorodeoxyuridine monophosphate (FdUMP) which inhibits the enzyme thymidylate synthase (TYMS), an important part of the folate-homocysteine cycle and purine and pyrimidine synthesis The conversion of 5-FU to FdUMP can occur via thymidylate phosphorylase (TYMP) to fluorodeoxyuridine (FUDR) and then by the action of thymidine kinase to FdUMP or indirectly via fluorouridine monophosphate (FUMP) or fluroridine (FUR) to fluorouridine diphosphate (FUDP) and then ribonucleotide reductase action to FdUDP and FdUMP. FUDP and FdUDP can also be converted to FUTP and FdUTP and incorporated into RNA and DNA respectively which also contributes to the pharmacodynamic actions of fluoropyrimidines.
Sources: PharmGKB:Fluoropyrimidine Pharmacokinetics, PharmGKB:Fluoropyrimidine Pharmacodynamics, Wikipedia:Fluorouracil
Proteins on this pathway have targeted assays available via the CPTAC Assay PortalQuality Tags
Ontology Terms
Bibliography
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- Marsh S; ''Thymidylate synthase pharmacogenetics.''; Invest New Drugs, 2005 PubMed Europe PMC Scholia
- Huang ZH, Hua D, Li LH, Zhu JD; ''Prognostic role of p53 codon 72 polymorphism in gastric cancer patients treated with fluorouracil-based adjuvant chemotherapy.''; J Cancer Res Clin Oncol, 2008 PubMed Europe PMC Scholia
- Peters EJ, Kraja AT, Lin SJ, Yen-Revollo JL, Marsh S, Province MA, McLeod HL; ''Association of thymidylate synthase variants with 5-fluorouracil cytotoxicity.''; Pharmacogenet Genomics, 2009 PubMed Europe PMC Scholia
- Hagmann W, Jesnowski R, Faissner R, Guo C, Löhr JM; ''ATP-binding cassette C transporters in human pancreatic carcinoma cell lines. Upregulation in 5-fluorouracil-resistant cells.''; Pancreatology, 2009 PubMed Europe PMC Scholia
- Yen-Revollo JL, Goldberg RM, McLeod HL; ''Can inhibiting dihydropyrimidine dehydrogenase limit hand-foot syndrome caused by fluoropyrimidines?''; Clin Cancer Res, 2008 PubMed Europe PMC Scholia
- Humeniuk R, Menon LG, Mishra PJ, Gorlick R, Sowers R, Rode W, Pizzorno G, Cheng YC, Kemeny N, Bertino JR, Banerjee D; ''Decreased levels of UMP kinase as a mechanism of fluoropyrimidine resistance.''; Mol Cancer Ther, 2009 PubMed Europe PMC Scholia
- Longley DB, Harkin DP, Johnston PG; ''Incorporation of 3H-dibromodulcitol and 3H-dianhydrodulcitol into ascites tumor cells. Autoradiographic study.''; Neoplasma, 1976 PubMed Europe PMC Scholia
- Wang W, Cassidy J, O'Brien V, Ryan KM, Collie-Duguid E; ''Mechanistic and predictive profiling of 5-Fluorouracil resistance in human cancer cells.''; Cancer Res, 2004 PubMed Europe PMC Scholia
- Miwa M, Ura M, Nishida M, Sawada N, Ishikawa T, Mori K, Shimma N, Umeda I, Ishitsuka H; ''Design of a novel oral fluoropyrimidine carbamate, capecitabine, which generates 5-fluorouracil selectively in tumours by enzymes concentrated in human liver and cancer tissue.''; Eur J Cancer, 1998 PubMed Europe PMC Scholia
- Nordgard SH, Alnaes GI, Hihn B, Lingjaerde OC, Liestøl K, Tsalenko A, Sørlie T, Lønning PE, Børresen-Dale AL, Kristensen VN; ''Pathway based analysis of SNPs with relevance to 5-FU therapy: relation to intratumoral mRNA expression and survival.''; Int J Cancer, 2008 PubMed Europe PMC Scholia
- Diasio RB, Harris BE; ''Clinical pharmacology of 5-fluorouracil.''; Clin Pharmacokinet, 1989 PubMed Europe PMC Scholia
- De Angelis PM, Svendsrud DH, Kravik KL, Stokke T; ''Cellular response to 5-fluorouracil (5-FU) in 5-FU-resistant colon cancer cell lines during treatment and recovery.''; Mol Cancer, 2006 PubMed Europe PMC Scholia
- Gmeiner WH; ''Novel chemical strategies for thymidylate synthase inhibition.''; Curr Med Chem, 2005 PubMed Europe PMC Scholia
- Behera RK, Nayak R; ''Expression profiling of nucleotide metabolism-related genes in human breast cancer cells after treatment with 5-fluorouracil.''; Cancer Invest, 2009 PubMed Europe PMC Scholia
- Yuan J, Lv H, Peng B, Wang C, Yu Y, He Z; ''Role of BCRP as a biomarker for predicting resistance to 5-fluorouracil in breast cancer.''; Cancer Chemother Pharmacol, 2009 PubMed Europe PMC Scholia
- Huang MY, Fang WY, Lee SC, Cheng TL, Wang JY, Lin SR; ''ERCC2 2251A>C genetic polymorphism was highly correlated with early relapse in high-risk stage II and stage III colorectal cancer patients: a preliminary study.''; BMC Cancer, 2008 PubMed Europe PMC Scholia
- Cao D, Russell RL, Zhang D, Leffert JJ, Pizzorno G; ''Uridine phosphorylase (-/-) murine embryonic stem cells clarify the key role of this enzyme in the regulation of the pyrimidine salvage pathway and in the activation of fluoropyrimidines.''; Cancer Res, 2002 PubMed Europe PMC Scholia
- Ruzzo A, Graziano F, Loupakis F, Santini D, Catalano V, Bisonni R, Ficarelli R, Fontana A, Andreoni F, Falcone A, Canestrari E, Tonini G, Mari D, Lippe P, Pizzagalli F, Schiavon G, Alessandroni P, Giustini L, Maltese P, Testa E, Menichetti ET, Magnani M; ''Pharmacogenetic profiling in patients with advanced colorectal cancer treated with first-line FOLFIRI chemotherapy.''; Pharmacogenomics J, 2008 PubMed Europe PMC Scholia
- Iacopetta B, Kawakami K, Watanabe T; ''Predicting clinical outcome of 5-fluorouracil-based chemotherapy for colon cancer patients: is the CpG island methylator phenotype the 5-fluorouracil-responsive subgroup?''; Int J Clin Oncol, 2008 PubMed Europe PMC Scholia
- Karasawa H, Miura K, Fujibuchi W, Ishida K, Kaneko N, Kinouchi M, Okabe M, Ando T, Murata Y, Sasaki H, Takami K, Yamamura A, Shibata C, Sasaki I; ''Down-regulation of cIAP2 enhances 5-FU sensitivity through the apoptotic pathway in human colon cancer cells.''; Cancer Sci, 2009 PubMed Europe PMC Scholia
- Boyer J, Allen WL, McLean EG, Wilson PM, McCulla A, Moore S, Longley DB, Caldas C, Johnston PG; ''Pharmacogenomic identification of novel determinants of response to chemotherapy in colon cancer.''; Cancer Res, 2006 PubMed Europe PMC Scholia
- Sobrero AF, Aschele C, Bertino JR; ''Fluorouracil in colorectal cancer--a tale of two drugs: implications for biochemical modulation.''; J Clin Oncol, 1997 PubMed Europe PMC Scholia
- An Q, Robins P, Lindahl T, Barnes DE; ''5-Fluorouracil incorporated into DNA is excised by the Smug1 DNA glycosylase to reduce drug cytotoxicity.''; Cancer Res, 2007 PubMed Europe PMC Scholia
- Farrell JJ, Elsaleh H, Garcia M, Lai R, Ammar A, Regine WF, Abrams R, Benson AB, Macdonald J, Cass CE, Dicker AP, Mackey JR; ''Human equilibrative nucleoside transporter 1 levels predict response to gemcitabine in patients with pancreatic cancer.''; Gastroenterology, 2009 PubMed Europe PMC Scholia
- Sengupta S, den Boon JA, Chen IH, Newton MA, Stanhope SA, Cheng YJ, Chen CJ, Hildesheim A, Sugden B, Ahlquist P; ''MicroRNA 29c is down-regulated in nasopharyngeal carcinomas, up-regulating mRNAs encoding extracellular matrix proteins.''; Proc Natl Acad Sci U S A, 2008 PubMed Europe PMC Scholia
- van Kuilenburg AB, Meinsma R, Zonnenberg BA, Zoetekouw L, Baas F, Matsuda K, Tamaki N, van Gennip AH; ''Dihydropyrimidinase deficiency and severe 5-fluorouracil toxicity.''; Clin Cancer Res, 2003 PubMed Europe PMC Scholia
- Yuan JH, Cheng JQ, Jiang LY, Ji WD, Guo LF, Liu JJ, Xu XY, He JS, Wang XM, Zhuang ZX; ''Breast cancer resistance protein expression and 5-fluorouracil resistance.''; Biomed Environ Sci, 2008 PubMed Europe PMC Scholia
- Thomas HR, Ezzeldin HH, Guarcello V, Mattison LK, Fridley BL, Diasio RB; ''Genetic regulation of dihydropyrimidinase and its possible implication in altered uracil catabolism.''; Pharmacogenet Genomics, 2007 PubMed Europe PMC Scholia
- Jensen SA, Vainer B, Witton CJ, Jørgensen JT, Sørensen JB; ''Prognostic significance of numeric aberrations of genes for thymidylate synthase, thymidine phosphorylase and dihydrofolate reductase in colorectal cancer.''; Acta Oncol, 2008 PubMed Europe PMC Scholia
- De Mattia E, Toffoli G; ''C677T and A1298C MTHFR polymorphisms, a challenge for antifolate and fluoropyrimidine-based therapy personalisation.''; Eur J Cancer, 2009 PubMed Europe PMC Scholia
- Kunz C, Focke F, Saito Y, Schuermann D, Lettieri T, Selfridge J, Schär P; ''Base excision by thymine DNA glycosylase mediates DNA-directed cytotoxicity of 5-fluorouracil.''; PLoS Biol, 2009 PubMed Europe PMC Scholia
- Kidd EA, Yu J, Li X, Shannon WD, Watson MA, McLeod HL; ''Variance in the expression of 5-Fluorouracil pathway genes in colorectal cancer.''; Clin Cancer Res, 2005 PubMed Europe PMC Scholia
- Kobayashi Y, Ohshiro N, Sakai R, Ohbayashi M, Kohyama N, Yamamoto T; ''Transport mechanism and substrate specificity of human organic anion transporter 2 (hOat2 [SLC22A7]).''; J Pharm Pharmacol, 2005 PubMed Europe PMC Scholia
- Wu X, Gu J, Wu TT, Swisher SG, Liao Z, Correa AM, Liu J, Etzel CJ, Amos CI, Huang M, Chiang SS, Milas L, Hittelman WN, Ajani JA; ''Genetic variations in radiation and chemotherapy drug action pathways predict clinical outcomes in esophageal cancer.''; J Clin Oncol, 2006 PubMed Europe PMC Scholia
- Sakamoto E, Tsukioka S, Oie S, Kobunai T, Tsujimoto H, Sakamoto K, Okayama Y, Sugimoto Y, Oka T, Fukushima M; ''Folylpolyglutamate synthase and gamma-glutamyl hydrolase regulate leucovorin-enhanced 5-fluorouracil anticancer activity.''; Biochem Biophys Res Commun, 2008 PubMed Europe PMC Scholia
- Gusella M, Padrini R; ''G>C SNP of thymidylate synthase with respect to colorectal cancer.''; Pharmacogenomics, 2007 PubMed Europe PMC Scholia
- Tsujie M, Nakamori S, Nakahira S, Takahashi Y, Hayashi N, Okami J, Nagano H, Dono K, Umeshita K, Sakon M, Monden M; ''Human equilibrative nucleoside transporter 1, as a predictor of 5-fluorouracil resistance in human pancreatic cancer.''; Anticancer Res, 2007 PubMed Europe PMC Scholia
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