Thymidine As an Anticancer Agent, Alone or in Combination. A Biochemical Appraisal

Overview

Journal Cancer Chemother Pharmacol

Specialty Oncology

Date 1982 Dec 1

PMID 6186411

Citations 3

Authors

P H Ellims

Affiliations

Soon will be listed here.

Abstract

The value of thymidine as a cytotoxic drug alone or in combination with other pyrimidine antimetabolites has received considerable attention in recent years. In this paper, the biochemical basis for the cytotoxicity of thymidine and its interaction with other pyrimidine antimetabolites is described. It is indicated that early clinical trials have largely failed to substantiate data from experimental studies that have shown thymidine to be an effective antimetabolite and capable of potentiating the antineoplastic effect of several other agents. It is suggested that tumours likely to respond to thymidine alone or in combination may be identified by measuring in clinical tumour specimens known biochemical determinants of thymidine efficacy.

Citing Articles

NAD regulates nucleotide metabolism and genomic DNA replication.

Munk S, Merchut-Maya J, Adelantado Rubio A, Hall A, Pappas G, Milletti G Nat Cell Biol. 2023; 25(12):1774-1786.

PMID: 37957325 PMC: 10709141. DOI: 10.1038/s41556-023-01280-z.

A combination of 5-fluorouracil and thymidine in advanced colorectal carcinoma.

Sternberg A, Petrelli N, Au J, Rustum Y, Mittelman A, Creaven P Cancer Chemother Pharmacol. 1984; 13(3):218-22.

PMID: 6488442 DOI: 10.1007/BF00269033.

3-Deazauridine (NSC 126849): an interesting modulator of biochemical response.

Moriconi W, Slavik M, Taylor S Invest New Drugs. 1986; 4(1):67-84.

PMID: 2422137 DOI: 10.1007/BF00172020.

References

Lee S, GIOVANELLA B, STEHLIN Jr J . Effect of excess thymidine on the growth of human melanoma cells transplanted in thymus deficient nude mice. Cancer Lett. 1977; 3(3-4):209-14. DOI: 10.1016/s0304-3835(77)95736-6. View

Myers C, Young R, Chabner B . Biochemical determinants of 5-fluorouracil response in vivo. The role of deoxyuridylate pool expansion. J Clin Invest. 1975; 56(5):1231-8. PMC: 301986. DOI: 10.1172/JCI108199. View

Tattersall M, Brown B, Frei 3rd E . The reversal of methotrexate toxicity by thymidine with maintenance of antitumour effects. Nature. 1975; 253(5488):198-200. DOI: 10.1038/253198a0. View

REICHARD P . From deoxynucleotides to DNA synthesis. Fed Proc. 1978; 37(1):9-14. View

Lee S, GIOVANELLA B, STEHLIN Jr J . Selective lethal effect of thymidine on human and mouse tumor cells. J Cell Physiol. 1977; 92(3):401-5. DOI: 10.1002/jcp.1040920308. View

Jackson R . Modulation of methotrexate toxicity by thymidine: sequence-dependent biochemical effects. Mol Pharmacol. 1980; 18(2):281-6. View

Kinahan J, Kowal E, GRINDEY G . Biochemical and antitumor effects of the combination of thymidine and 1-beta-D-arabinofuranosylcytosine against leukemia L1210. Cancer Res. 1981; 41(2):445-51. View

Howell S, Taetle R, Mendelsohn J . Thymidine as a chemotherapeutic agent: sensitivity of normal human marrow, peripheral blood T cells, and acute nonlymphocytic leukemia. Blood. 1980; 55(3):505-10. View

Momparler R, Goodman J . In vitro cytotoxic and biochemical effects of 5-aza-2'-deoxycytidine. Cancer Res. 1977; 37(6):1636-9. View

10.

Eriksson S, Thelander L, Akerman M . Allosteric regulation of calf thymus ribonucleoside diphosphate reductase. Biochemistry. 1979; 18(14):2948-52. DOI: 10.1021/bi00581a005. View

11.

Grant S, Lehman C, Cadman E . Enhancement of 1-beta-D-arabinofuranosylcytosine accumulation within L1210 cells and increased cytotoxicity following thymidine exposure. Cancer Res. 1980; 40(5):1525-31. View

12.

ENSMINGER W, Frei 3rd E . The prevention of methotrexate toxicity by thymidine infusions in humans. Cancer Res. 1977; 37(6):1857-63. View

13.

de Saint Vincent B, Dechamps M, Buttin G . The modulation of the thymidine triphosphate pool of Chinese hamster cells by dCMP deaminase and UDP reductase. Thymidine auxotrophy induced by CTP in dCMP deaminase-deficient lines. J Biol Chem. 1980; 255(1):162-7. View

14.

Spiegelman S, Nayak R, Sawyer R, Stolfi R, Martin D . Potentiation of the anti-tumor activity of 5FU by thymidine and its correlation with the formation of (5FU)RNA. Cancer. 1980; 45(5 Suppl):1129-34. DOI: 10.1002/1097-0142(19800315)45:5+<1129::aid-cncr2820451317>3.0.co;2-i. View

15.

Kirkwood J, Ensminger W, Rosowsky A, Papathanasopoulos N, Frei 3rd E . Comparison of pharmacokinetics of 5-fluorouracil and 5-fluorouracil with concurrent thymidine infusions in a Phase I trial. Cancer Res. 1980; 40(1):107-13. View

16.

Grant S, Rauscher 3rd F, Margolin J, Cadman E . Dose- and schedule-dependent activation and drug synergism between thymidine and 5-aza-2'-deoxycytidine in a human promyelocytic leukemia cell line. Cancer Res. 1982; 42(2):519-24. View

17.

Kufe D, Beardsley P, Karp D, Parker L, Rosowsky A, Canellos G . High-dose thymidine infusions in patients with leukemia and lymphoma. Blood. 1980; 55(4):580-9. View

18.

Howell S, ENSMINGER W, Krishan A, Frei 3rd E . Thymidine rescue of high-dose methotrexate in humans. Cancer Res. 1978; 38(2):325-30. View

19.

Kinahan J, Otten M, GRINDEY G . Evaluation of ribonucleoside and deoxyribonucleoside triphosphate pools in cultured leukemia cells during exposure to methotrexate or methotrexate plus thymidine. Cancer Res. 1979; 39(9):3531-9. View

20.

XEROS N . Deoxyriboside control and synchronization of mitosis. Nature. 1962; 194:682-3. DOI: 10.1038/194682a0. View