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Novel Approaches to Selective Treatments of Human Solid Tumors pp 143–151Cite as

Regulation of Thymidylate Synthase in Human Colon Cancer Cells Treated with 5-Fluorouracil and Interferon-Gamma

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 339))

Abstract

5-Fluorouracil (5-FU) remains, at present, the single most active agent for the treatment of human colorectal cancer. When used as a single agent against advanced disease, it is associated with an overall response rate of only 15–20%, and therapy with 5-FU is unable to prolong the survival of treated patients [1–3]. Since few other agents have been identified for the treatment of human colorectal cancer, considerable attention has focused on elucidating the basic mechanisms of 5-FU action. The cytotoxic effects of 5-FU have been traditionally ascribed either to inhibition of the critical target enzyme thymidylate synthase (TS) by the 5-FU metabolite 5-fluoro-2′-deoxyuridine-5′-monophosphate (FdUMP) with subsequent inhibition of thymidylate and DNA biosynthesis, to incorporation of the 5-FU metabolite 5-fluorouridine-5′-triphosphate (FUTP) into RNA with resultant inhibition of RNA synthesis and function, or to incorporation of the 5-FU metabolite 5-fluoro-2′-deoxyuridine-5′-triphosphate (FdUTP) into DNA with resultant inhibition of DNA synthesis and function [1–11]. The relative contribution of each of these metabolic processes remains unclear at this time.

Address reprint request to Daniel S. Martin, Cancer Research,89-15 Woodhaven Blvrd., Woodhaven, NY 11421

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Authors and Affiliations

  1. NCI-Navy Medical Oncology Branch, National Cancer Institute,NIHNMOB 8/5101-Naval Hospital, Bethesda, Maryland, 20889, USA

    Edward Chu & Carmen J. Allegra

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  1. Edward Chu
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  2. Carmen J. Allegra
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  1. Grace Cancer Drug Center, Roswell Park Cancer Institute, Buffalo, New York, USA

    Youcef M. Rustum

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Chu, E., Allegra, C.J. (1993). Regulation of Thymidylate Synthase in Human Colon Cancer Cells Treated with 5-Fluorouracil and Interferon-Gamma. In: Rustum, Y.M. (eds) Novel Approaches to Selective Treatments of Human Solid Tumors. Advances in Experimental Medicine and Biology, vol 339. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-2488-5_16

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  • DOI: https://doi.org/10.1007/978-1-4615-2488-5_16

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-6060-5

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