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Anthracyclines and Bortezomib

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Proteasome Inhibitors in Cancer Therapy

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

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Abstract

Anthracycline chemotherapeutics display activity against a broad range of cancers and are therefore in clinical use for therapy of patients with both hematologic malignancies and solid tumors. However, these drugs have the ability to activate pathways such as nuclear factor-κB and p44/42 mitogen-activated protein kinase which play roles in inducible chemoresistance and promote tumor cell survival. Because proteasome inhibitors block activation of these pathways, it is possible that combinations of an anthracycline and a proteasome inhibitor could induce higher levels of tumor cell apoptosis. Furthermore, other mechanisms of resistance to anthracyclines, such as P-glycloprotein expression and downregulation of topoisomerase II, may also be abrogated by proteasome inhibitors, further supporting the development of such regimens. This chapter describes some of the molecular mechanisms by which addition of a proteasome inhibitor to an anthracycline could result in enhanced antitumor efficacy. In addition, the available preclinical and early clinical data are critically reviewed, to afford the reader some insight into the promise of this area of investigation.

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Authors
  1. Robert Z. Orlowski
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Editors and Affiliations

  1. Infinity Pharmaceuticals Inc., Cambridge, MA, USA

    Julian Adams PhD

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© 2004 Springer Science+Business Media New York

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Orlowski, R.Z. (2004). Anthracyclines and Bortezomib. In: Adams, J. (eds) Proteasome Inhibitors in Cancer Therapy. Cancer Drug Discovery and Development. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-794-9_14

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  • DOI: https://doi.org/10.1007/978-1-59259-794-9_14

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61737-452-4

  • Online ISBN: 978-1-59259-794-9

  • eBook Packages: Springer Book Archive

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