Mechanisms of action of FdUMP[10]: Metabolite activation and thymidylate synthase inhibition

Oncology Reports

Volumn 18, Issue 1, 2007, Pages 287-291

  Bijnsdorp, I V ^a   Comijn, E M ^a   Padron, J M ^a   Gmeiner, W H ^b   Peters, G J ^a  

^a VU UNIVERSITY MEDICAL CENTER   (Netherlands)

^b WAKE FOREST SCHOOL OF MEDICINE   (United States)

Author keywords

5 fluorouracil; FdUMP 10 ; Thymidine kinase; Thymidylate synthase

Indexed keywords

ANTINEOPLASTIC AGENT; DRUG DERIVATIVE; ENZYME INHIBITOR; FLOXURIDINE PHOSPHATE; FLUOROURACIL; FOLIC ACID ANTAGONIST; GLUTAMIC ACID DERIVATIVE; GUANINE; PEMETREXED; QUINAZOLINE DERIVATIVE; RALTITREXED; THIOPHENE DERIVATIVE; THYMIDYLATE SYNTHASE;

ANIMAL; ARTICLE; CELL CULTURE; CHEMICAL STRUCTURE; DRUG ANTAGONISM; DRUG SCREENING; ENZYMOLOGY; EXPERIMENTAL NEOPLASM; METABOLISM; MOUSE; PATHOLOGY;

ANIMALS; ANTINEOPLASTIC AGENTS; DRUG SCREENING ASSAYS, ANTITUMOR; ENZYME INHIBITORS; FLUORODEOXYURIDYLATE; FLUOROURACIL; FOLIC ACID ANTAGONISTS; GLUTAMATES; GUANINE; MAMMARY NEOPLASMS, EXPERIMENTAL; MICE; MOLECULAR STRUCTURE; QUINAZOLINES; THIOPHENES; THYMIDYLATE SYNTHASE; TUMOR CELLS, CULTURED;

EID: 34548017882     PISSN: 1021335X     EISSN: 17912431     Source Type: Journal    
DOI: 10.3892/or.18.1.287     Document Type: Article

References (34)

1. Moertel CG: Chemotherapy for colorectal cancer. N Engl J Med 330: 1136-1142, 1994.
2. Peters GJ and Kohne CH: Fluoropyrimidines as antifolate drugs. In: Antifolate Drugs in Cancer Therapy. Jackman AL (ed). Humana Press Inc., pp101-145, 1999.
3. Peters GJ and Jansen G: Resistance to antimetabolites. In: Principles of Antineoplastic Drug Development and Pharmacology. Schilsky RL, Milano GA and Ratain MJ (eds). Marcel Dekker, Inc., New York, pp543-585, 1996.
4. Liu J, Skradis A, Kolar C, Kolath J, Anderson J, Lawson T, Talmadge J and Gmeiner WH: Increased cytotoxicity and decreased in vivo toxicity of FdUMP[10] relative to 5-FU. Nucleosides Nucleotides 18: 1789-1802, 1999. (Pubitemid 29364652)
5. Liu J, Kolar C, Lawson TA and Gmeiner WH: Targeted drug delivery to chemoresistant cells: folic acid derivatization of FdUMP[10] enhances cytotoxicity toward 5-FU-resistant human colorectal tumor cells. J Org Chem 66: 5655-5663, 2001. (Pubitemid 32867461)
6. Liu C, Willingham M, Liu J and Gmeiner WH: Efficacy and safety of FdUMP[10] in treatment of HT-29 human colon cancer xenografts. Int J Oncol 21: 303-308, 2002.
7. Peters GJ and Ackland SP: New antimetabolites in preclinical and clinical development. Exp Opin Invest Drugs 5: 637-679, 1996.
8. Bertino JR: Karnofsky memorial lecture. Ode to methotrexate. J Clin Oncol 11: 5-14, 1993.
9. Chu E, Callender MA, Farrell MP and Schmitz JC: Thymidylate synthase inhibitors as anticancer agents: from bench to bedside. Cancer Chemother Pharmacol 52 (Suppl. 1): S80-S89, 2003. (Pubitemid 37047028)
10. Walling J: From methotrexate to pemetrexed and beyond. A review of the pharmacodynamic and clinical properties of antifolates. Invest New Drugs 24: 37-77, 2006.
11. Duch DS, Banks S, Dev IK, Dickerson SH, Ferone R, Heath LS, Humphreys J, Knick V, Pendergast W and Singer S: Biochemical and cellular pharmacology of 1843U89, a novel benzoquinazoline inhibitor of thymidylate synthase. Cancer Res 53: 810-818, 1993. (Pubitemid 23077867)
12. Rafi I, Taylor GA, Calvete JA, Boddy AV, Balmanno K, Bailey N, Lind M, Calvert AH, Webber S and Jackson RC: Clinical pharmacokinetic and pharmacodynamic studies with the nonclassical antifolate thymidylate synthase inhibitor 3,4-dihydro-2-amino-6-methyl-4-oxo-5-(4-pyridylthio)-quinazolone dihydrochloride (AG337) given by 24-h continuous intravenous infusion. Clin Cancer Res 1: 1275-1284, 1995.
13. Bottomley A, Gaafa R, Manegold C, Burgers S, Coens C, Legrand C, Vincent M, Giaccone G and van Meerbeeck J: Short-term treatment-related symptoms and quality of life: results from an international randomized phase III study of cisplatin with or without raltitrexed in patients with malignant pleural mesothelioma: an EORTC Lung-Cancer Group and National Cancer Institute, Canada, Intergroup Study. J Clin Oncol 24: 1435-1442, 2006. (Pubitemid 46622010)
14. Ceresoli GL, Zucali PA, Favaretto AG, Grossi F, Bidoli P, Del Conte G, Ceribelli A, Bearz A, Morenghi E, Cavina R, Marangolo M, Parra HJ and Santoro A: Phase II study of pemetrexed plus carboplatin in malignant pleural mesothelioma. J Clin Oncol 24: 1443-1448, 2006. (Pubitemid 46622011)
15. Hochster H, Kettner E, Kroning H, Becker K, Lordick F, Ramanathan RK, Macdonald J, Hong S, John W and Schmoll HJ: Phase I/II dose-escalation study of pemetrexed plus irinotecan in patients with advanced colorectal cancer. Clin Colorectal Cancer 5: 257-262, 2005.
16. Maroun JA, Jonker D, Seymour L, Goel R, Vincent M, Kocha W, Cripps C, Fisher B, Lister D, Malpage A and Chiritescu G: A National Cancer Institute of Canada Clinical Trials Group Study - IND.135: phase I/II study of irinotecan (camptosar), oxaliplatin and raltitrexed (tomudex) (COT) in patients with advanced colorectal cancer. Eur J Cancer 42: 193-199, 2006. (Pubitemid 43083489)
17. Ayusawa D, Koyama H and Seno T: Resistance to methotrexate in thymidylate synthetase-deficient mutants of cultured mouse mammary tumor FM3A cells. Cancer Res 41: 1497-1501, 1981. (Pubitemid 11127589)
18. Keepers YP, Pizao PE, Peters GJ, van Ark-Otte J, Winograd B, and Pinedo HM: Comparison of the sulforhodamine B protein and tetrazolium (MTT) assays for in vitro chemosensitivity testing. Eur J Cancer 27: 897-900, 1991.
19. Peters GJ, Laurensse E, Leyva A, Lankelma J and Pinedo HM: Sensitivity of human, murine, and rat cells to 5-fluorouracil and 5′-deoxy-5- fluorouridine in relation to drug-metabolizing enzymes. Cancer Res 46: 20-28, 1986. (Pubitemid 16189022)
20. Rots MG, Pieters R, Kaspers GJ, van Zantwijk CH, Noordhuis P, Mauritz R, Veerman AJ, Jansen G and Peters GJ: Differential methotrexate resistance in childhood T- versus common/preB-acute lymphoblastic leukemia can be measured by an in situ thymidylate synthase inhibition assay, but not by the MTT assay. Blood 93: 1067-1074, 1999. (Pubitemid 29067873)
21. Peters GJ, Laurensse E, Leyva A and Pinedo HM: Purine nucleosides as cell-specific modulators of 5-fluorouracil metabolism and cytotoxicity. Eur J Cancer Clin Oncol 23: 1869-1881, 1987. (Pubitemid 18013328)
22. Peters GJ, van Groeningen CJ, Laurensse EJ and Pinedo HM: Thymidylate synthase from untreated human colorectal cancer and colonic mucosa: enzyme activity and inhibition by 5-fluoro-2′-deoxy-uridine-5′- monophosphate. Eur J Cancer 27: 263-267, 1991.
23. Van Triest B, Pinedo HM, van Hensbergen Y, Smid K, Telleman F, Schoenmakers PS, van der Wilt CL, van Laar JA, Noordhuis P, Jansen G and Peters GJ: Thymidylate synthase level as the main predictive parameter for sensitivity to 5-fluorouracil, but not for folate-based thymidylate synthase inhibitors, in 13 non-selected colon cancer cell lines. Clin Cancer Res 5: 643-654, 1999. (Pubitemid 29131976)
24. Gorlick R and Bertino JR: Drug resistance in colon cancer. Semin Oncol 26: 606-611, 1999. (Pubitemid 30013267)
25. Mader RM, Muller M and Steger GG: Resistance to 5-fluorouracil. Gen Pharmacol 31: 661-666, 1998. (Pubitemid 28520040)
26. Rustum YM: Clinical implications of 5-FU modulation. Oncology 13: 22-25, 1999.
27. Shih C, Habeck LL, Mendelsohn LG, Chen VJ and Schultz RM: Multiple folate enzyme inhibition: mechanism of a novel pyrrolopyrimidine-based antifolate LY231514 (MTA). Adv Enzyme Regul 38: 135-152, 1998. (Pubitemid 28381388)
28. Shih C, Chen VJ, Gossett LS, Gates SB, MacKellar WC, Habeck LL, Shackelford KA, Mendelsohn LG, Soose DJ, Patel VF, Andis SL, Bewley JR, Rayl EA, Moroson BA, Beardsley GP, Kohler W, Ratnam M and Schultz RM: LY231514, a pyrrolo[2,3-d]pyrimidine-based antifolate that inhibits multiple folate-requiring enzymes. Cancer Res 57: 1116-1123, 1997. (Pubitemid 27138611)
29. Spears CP, Gustavsson BG, Berne M, Frosing R, Bernstein L and Hayes AA: Mechanisms of innate resistance to thymidylate synthase inhibition after 5-fluorouracil. Cancer Res 48: 5894-5900, 1988.
30. Ford HE, Mitchell F, Cunningham D, Farrugia DC, Hill ME, Rees C, Calvert AH, Judson IR and Jackman AL: Patterns of elevation of plasma 2′-deoxyuridine, a surrogate marker of thymidylate synthase (TS) inhibition, after administration of two different schedules of 5-fluorouracil and the specific TS inhibitors raltitrexed (Tomudex) and ZD9331. Clin Cancer Res 8: 103-109, 2002. (Pubitemid 34101464)
31. Forsthoefel AM, Pena MM, Xing YY, Rafique Z and Berger FG: Structural determinants for the intracellular degradation of human thymidylate synthase. Biochemistry 43: 1972-1979, 2004. (Pubitemid 38233259)
32. Jarmula A, Cieplak P, Les A and Rode W: Relative free energies of binding to thymidylate synthase of 2- and/or 4-thio and/or 5-fluoro analogues of dUMP. J Comput Aided Mol Des 17: 699-710, 2003. (Pubitemid 38344472)
33. Myers CE, Young RC and Chabner BA: Biochemical determinants of 5-fluorouracil response in vivo . The role of deoxyuridylate pool expansion. J Clin Invest 56: 1231-1238, 1975.
34. Peters GJ, Backus HH, Freemantle S, Van Triest B, Codacci-Pisanelli G, van der Wilt CL, Smid K, Lunec J, Calvert AH, Marsh S, McLeod HL, Bloemena E, Meijer S, Jansen G, van Groeningen CJ and Pinedo HM: Induction of thymidylate synthase as a 5-fluorouracil resistance mechanism. Biochim Biophys Acta 1587: 194-205, 2002. (Pubitemid 34655788) Health