Methotrexate resistant cells at targets for selective chemotherapy

J. R. Bertino, E. Mini, A. Sobrero, B. A. Moroson, T. Love, M. Jastreboff, M. Carmen, S. Srimatkandada, S. Dube

Research output: Contribution to journalArticle

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Abstract

Strategies that are selective for eradicating methotrexate resistant cells are described. These strategies have been developed based on knowledge of the mechanism of drug resistance encountered in experimental systems and in the clinic. Drug resistance to methotrexate in experimental tumors is commonly due to either gene amplification (dihydrofolate reductase) or to impaired transport of methotrexate. While no effective drugs or methods to prevent gene amplification have been described, the concept of developing "pro drugs", i.e. a drug that is selectively reduced by dihydrofolate reductase to an inhibitor of another critical folate enzyme (thymidylate synthase, methionine synthetase, folylpolyglutamte synthetase) remains worthwhile. Second generation antifolates such as trimetrexate which are effective vs methotrexate transport resistant cells have already been developed and are in clinical trial.

Original languageEnglish
Pages (from-to)3-11
Number of pages9
JournalAdvances in Enzyme Regulation
Volume24
Issue numberC
DOIs
Publication statusPublished - 1985

Fingerprint

Chemotherapy
Methotrexate
Folic Acid Antagonists
Drug Therapy
Tetrahydrofolate Dehydrogenase
Gene Amplification
Drug Resistance
Pharmaceutical Preparations
Trimetrexate
5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase
Thymidylate Synthase
Prodrugs
Ligases
Folic Acid
Tumors
Clinical Trials
Enzymes
Neoplasms

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Cite this

Bertino, J. R., Mini, E., Sobrero, A., Moroson, B. A., Love, T., Jastreboff, M., ... Dube, S. (1985). Methotrexate resistant cells at targets for selective chemotherapy. Advances in Enzyme Regulation, 24(C), 3-11. https://doi.org/10.1016/0065-2571(85)90066-4

Methotrexate resistant cells at targets for selective chemotherapy. / Bertino, J. R.; Mini, E.; Sobrero, A.; Moroson, B. A.; Love, T.; Jastreboff, M.; Carmen, M.; Srimatkandada, S.; Dube, S.

In: Advances in Enzyme Regulation, Vol. 24, No. C, 1985, p. 3-11.

Research output: Contribution to journalArticle

Bertino, JR, Mini, E, Sobrero, A, Moroson, BA, Love, T, Jastreboff, M, Carmen, M, Srimatkandada, S & Dube, S 1985, 'Methotrexate resistant cells at targets for selective chemotherapy', Advances in Enzyme Regulation, vol. 24, no. C, pp. 3-11. https://doi.org/10.1016/0065-2571(85)90066-4
Bertino, J. R. ; Mini, E. ; Sobrero, A. ; Moroson, B. A. ; Love, T. ; Jastreboff, M. ; Carmen, M. ; Srimatkandada, S. ; Dube, S. / Methotrexate resistant cells at targets for selective chemotherapy. In: Advances in Enzyme Regulation. 1985 ; Vol. 24, No. C. pp. 3-11.
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