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Deoxynucleoside Analogs In Cancer Therapy pp 81–108Cite as

Nucleotidases and Nucleoside Analog Cytotoxicity

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Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

Abstract

Nucleoside analogs are an important part of therapeutic strategies in a broad range of diseases, especially cancer and viral infections. Most nucleoside analogs need to be phosphorylated to attain full clinical potency; thus, knowledge of the metabolism of this class of drugs is required to improve their clinical use. The 5′-nucleotidases are a family of enzymes that catalyze the final dephosphorylation step of nucleotides in the cell and, by opposing the activation step catalyzed by nucleoside kinases, initiate subsequent purine and pyrimidine catabolism. They also catalyze a critical step in nucleotide analog degradation; therefore, their expression and regulation in various tissues will likely have an impact on a nucleoside drug’s half-life in the human body. Numerous studies in vitro and in vivo indicate that increased expression of 5′_nucleotidase may decrease nucleoside analog activation and thereby contribute to drug resistance. Because cloned 5′_nucleotidases have been described in human tissues, it is not always possible to assess which particular 5′-nucleotidase is important in nucleoside drug catabolism. In this chapter, we review the properties of all cloned 5′-nucleotidases and the important role of these enzymes in nucleoside analog metabolism and clinical resistance.

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Authors and Affiliations

  1. Lineberger Comprehensive Cancer Center, Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC

    Sally Anne Hunsucker PhD

  2. George E. Becker Professor of Medicine, Comprehensive Cancer Center, Stanford University, Stanford, CA

    Beverly S. Mitchell MD, PhD

  3. VisiScience Corporation, Chapel Hill, NC

    Jozef Spychala PhD (President)

  4. Department of Pharmacology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC

    Jozef Spychala PhD (President)

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  1. Sally Anne Hunsucker PhD
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  2. Beverly S. Mitchell MD, PhD
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  3. Jozef Spychala PhD
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  1. VU University Medical Center Amsterdam, The Netherlands

    Godefridus J. Peters PhD (Professor of Medical Oncology) (Professor of Medical Oncology)

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Hunsucker, S.A., Mitchell, B.S., Spychala, J. (2006). Nucleotidases and Nucleoside Analog Cytotoxicity. In: Peters, G.J. (eds) Deoxynucleoside Analogs In Cancer Therapy. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1007/978-1-59745-148-2_4

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