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Reduced folates and fluoropyrimidine antitumor efficacy

  • Janet A. Houghton
  • Peter J. Houghton
Part of the Cancer Treatment and Research book series (CTAR, volume 42)

Abstract

During the last 30 years, the 5-fluoropyrimidines — 5-fluorouracil (FUra) and 5-fluoro-2′-deoxyuridine (FdUrd) — have become established as useful palliative agents in the treatment of certain malignancies in adults [1–3] and have been employed to a limited extent in children [4, 5]. They constitute some of the most extensively studied anticancer agents. However, the relevant mechanism(s) of action in human cancers in vivo achieved at pharmacologically tolerable dose levels remains the subject of considerable debate. For FUra, at least three mechanisms of cytotoxicity at the preclinical level have been proposed, each of which may be valid, dependent upon the model system used. It is because of this intense preclinical research into the metabolism of 5-fluoropyrimidines, and the interaction of metabolites with cellular macro-molecules, that various methods for modulating their potency, site of toxicity, and therapeutic utility have been proposed and tested both in model systems [6–10] and in clinical trials [11–14]. Our own interest in the concept of modulating 5-fluoropyrimidine action stems from studies in the late 1970s where attempts were made to elucidate mechanisms of intrinsic resistance to these agents, when human colon adenocarcinomas were heterografted into immune-deprived mice [15, 16].

Keywords

Ternary Complex Human Colon Adenocarcinoma Ehrlich Ascites Tumor Cell Thymidylate Synthetase Metastatic Colorectal Carcinoma 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Kluwer Academic Publishers 1989

Authors and Affiliations

  • Janet A. Houghton
  • Peter J. Houghton

There are no affiliations available

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