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Thioredoxin Reductase 1 as an Anticancer Drug Target

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Selenium

Abstract

Several genetic, biochemical and pharmacological studies suggest that the cytosolic selenoprotein thioredoxin reductase 1 (TrxR1, TXNRD1) can serve as a promising anticancer drug target. This notion is in part based upon potent and selective targeting of the selenocysteine residue in TrxR1 by electrophilic anticancer agents. Whereas normal somatic cells typically can survive without TrxR1, the metabolic and proliferative realignments associated with cancer increase the oxidative stress and thus an increased reliance upon reducing pathways in cancer cells, thereby increasing their dependence upon TrxR1 activity. Intricate functional links between TrxR1 and transcription factors such as Nrf2, NF-kB and p53, and interaction with other growth-promoting signaling pathways, further underpin anticancer therapies involving TrxR1 targeting. However, caveats exist, as some effects of TrxR1 inhibition may promote cancer rather than counteract its progression. Although encouraging advances are being made, the field is clearly not yet ready for clinical trials evaluating novel specific TrxR1 inhibitors in anticancer treatments. In this chapter we present and discuss the major aspects of this topic.

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Acknowledgements

Work of the authors has support from The National Institute of Health (NIH), Swedish Cancer Society, Swedish Research Council (Medicine and Natural Sciences sections), The Wenner-Gren Foundations, Knut and Alice Wallenberg Foundation, Montana State University and Karolinska Institutet.

Author information

Authors and Affiliations

  1. Division of Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 171 77, Stockholm, Sweden

    Edward E. Schmidt & Elias S. J. Arnér

  2. Microbiology and Immunology, Montana State University, Bozeman, MT, 59715, USA

    Edward E. Schmidt

Authors
  1. Edward E. Schmidt
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  2. Elias S. J. Arnér
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Corresponding author

Correspondence to Elias S. J. Arnér .

Editor information

Editors and Affiliations

  1. Mouse Cancer Genetics Program, National Institutes of Health, National Cancer Institute, Bethesda, Maryland, USA

    Dolph L. Hatfield

  2. Institut für Biochemie und Molekularbiologie, Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Nordrhein-Westfalen, Germany

    Ulrich Schweizer

  3. Department of Biological Sciences, Towson University, Towson, Maryland, USA

    Petra A. Tsuji

  4. Division of Genetics, Department of Medicine, Brigham and Women’s Hospital Harvard Medical School, Boston, Massachusetts, USA

    Vadim N. Gladyshev

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Schmidt, E.E., Arnér, E.S.J. (2016). Thioredoxin Reductase 1 as an Anticancer Drug Target. In: Hatfield, D., Schweizer, U., Tsuji, P., Gladyshev, V. (eds) Selenium. Springer, Cham. https://doi.org/10.1007/978-3-319-41283-2_16

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