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Molecular and Clinical Aspects of Proteasome Inhibition in the Treatment of Cancer

  • Chapter
Targeted Therapies in Cancer

Part of the book series: Recent Results in Cancer Research ((RECENTCANCER,volume 176))

Abstract

The proteasome is a multicatalytic threonine protease responsible for intracellular protein turnover in eukaryotic cells, including the processing and degradation of several proteins involved in cell cycle control and the regulation of apoptosis. Preclinical studies have shown that the treatment with proteasome inhibitors results in decreased proliferation, induction of apoptosis, and sensitization of tumor cells against conventional chemotherapeutic agents and irradiation. The effects were conferred to stabilization of p21, p27, Bax, p53, I-κB, and the resulting inhibition of the nuclear factor-κB (NF-κB) activation. Bortezomib is the first proteasome inhibitor that has entered clinical trials. In multiple myeloma, both the FDA (United States Food and Drug Administration) and EMEA (European Medicine Evaluation Agency) granted an approval for the use of bortezomib (Velcade, Millennium Pharmaceuticals, Cambridge, MA, USA) for the treatment of relapsed multiple myeloma. At present, clinical trials are examining the activity in a variety of solid tumors and hematological malignancies.

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Authors and Affiliations

  1. Department of Hematology and Oncology, Charité Universitätsmedizin Berlin, 10117, Berlin, Germany

    Ivana Zavrski MD, Christian Jakob MD, Martin Kaiser MD, Claudia Fleissner MD, Ulrike Heider MD & Orhan Sezer MD

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  1. Ivana Zavrski MD
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  2. Christian Jakob MD
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  3. Martin Kaiser MD
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  4. Claudia Fleissner MD
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  5. Ulrike Heider MD
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  6. Orhan Sezer MD
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  1. Institut für Pathologie, Charité Humboldt-Universität zu Berlin, Schumanstr. 20-21, 10117, Berlin, Germany

    Manfred Dietel

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Zavrski, I., Jakob, C., Kaiser, M., Fleissner, C., Heider, U., Sezer, O. (2007). Molecular and Clinical Aspects of Proteasome Inhibition in the Treatment of Cancer. In: Dietel, M. (eds) Targeted Therapies in Cancer. Recent Results in Cancer Research, vol 176. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-46091-6_14

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  • DOI: https://doi.org/10.1007/978-3-540-46091-6_14

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-46090-9

  • Online ISBN: 978-3-540-46091-6

  • eBook Packages: MedicineMedicine (R0)

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