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Nucleoside Transport Into Cells

Role of Nucleoside Transporters SLC28 and SLC29 in Cancer Chemotherapy

  • Chapter
Deoxynucleoside Analogs In Cancer Therapy

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

Abstract

Nucleosides are taken up into cells by either concentrative nucleoside transporter (CNT; SLC28 gene family) or equilibrative nucleoside transporter (ENT; SLC29 gene family) nucleoside transporters, which differ in their substrate selectivity and their energy requirements. Both nucleoside transporter families have also been involved in the transmembrane transport of nucleoside-derived compounds, many of them currently used in antiviral and antitumoral therapies; hence, there is necessity for good knowledge about the function of these transporters. Some key points in the pharmacological understanding of these transporters are addressed. There is a long list of nucleoside derivatives with clinical relevance that are known to be transported by one or several nucleoside transporters; however, until recently little was known about the structural determinants that allow the molecular recognition of the substrates by their transporters. This will be a key point in the development of rationally designed new drugs. Other aspects of nucleoside transporters are also relevant to their function as drug transporters. On the one hand, several polymorphisms have been described in CNT and ENT proteins that could affect their activity, although thorough functional analysis awaits. On the other hand, tissue distribution of these transporters is not homogeneous among tissues, and their expression can be tightly regulated, thus opening the possibility of over- or underexpression of a particular transporter in transformed cells, as has been reported in several cases. All these properties of nucleoside transporters determine their role in the bioavailability and cell sensitivity to anticancer drugs, and the first studies linking nucleoside transporter function to drug sensitivity and clinical outcome in cancer patients are now reported.

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Authors and Affiliations

  1. University of Barcelona, Barcelona, Spain

    Marçal Pastor-Anglada MSc, PhD (Professor of Biochemistry and Molecular Biology)

  2. Department of Biochemistry and Molecular Biology, University of Barcelona, Barcelona, Spain

    F. Javier Casado MSc, PhD (Associate Professor of Biochemistry and Molecular Biology)

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  1. Marçal Pastor-Anglada MSc, PhD
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  2. F. Javier Casado MSc, PhD
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Editors and Affiliations

  1. VU University Medical Center Amsterdam, The Netherlands

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

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Pastor-Anglada, M., Casado, F.J. (2006). Nucleoside Transport Into Cells. 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_1

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