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Epigenetic Treatment Options in Urothelial Carcinoma

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Urothelial Carcinoma

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1655))

Abstract

Mutations, dysregulation, and dysbalance of epigenetic regulators are especially frequent in urothelial carcinoma (UC) compared to other malignancies. Accordingly, targeting epigenetic regulators may provide a window of opportunity particularly in anticancer therapy of UC. In general, these epigenetic regulators comprise DNA methyltransferases and DNA demethylases (for DNA methylation), histone methyltransferases, and histone demethylases (for histone methylation) as well as acetyl transferases and histone deacetylases (for histone and non-histone acetylation).

As epigenetic regulators target a plethora of cellular functions and available inhibitors often inhibit enzymatic activity of more than one isoenzyme or may have further off-target effects, analysis of their functions in UC pathogenesis as well as of the antineoplastic capacity of according inhibitors should follow a multidimensional approach.

Here, we present our standard approach for the analysis of the cellular and molecular functions of individual HDAC enzymes, their suitability as treatment targets and for the evaluation of isoenzyme-specific HDAC inhibitors regarding their antineoplastic efficacy. This approach may also serve as prototype for the preclinical evaluation of other epigenetic treatment approaches.

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Acknowledgements and Conflicts of Interest

The HDAC project including the PhD position for M.P. was supported by grants from the Deutsche Forschungsgemeinschaft (NI 1398/1–1), the Forschungskommission of the Medical Faculty of the Heinrich-Heine-University (42/2015) and the Brigitte-und-Dr.-Konstanze-Wegener-Stiftung (project number 11) to G. N.. Further, G. N. reports receiving a commercial research grant (provision of experimental compound 4SC-202, publication costs) from 4SC.

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Authors and Affiliations

  1. Department of Urology, Medical Faculty, Heinrich Heine University Düsseldorf, Gebäude 13.72, Moorenstraße 5, Düsseldorf, Germany

    Maria Pinkerneil, Michèle J. Hoffmann & Günter Niegisch

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  1. Maria Pinkerneil
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  2. Michèle J. Hoffmann
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  3. Günter Niegisch
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Correspondence to Günter Niegisch .

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Editors and Affiliations

  1. Department of Urology, Heinrich Heine University, Düsseldorf, Germany

    Wolfgang A Schulz

  2. Department of Urology, Heinrich Heine University, Düsseldorf, Germany

    Michèle J. Hoffmann

  3. Department of Urology, Heinrich Heine University, Düsseldorf, Germany

    Günter Niegisch

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Pinkerneil, M., Hoffmann, M.J., Niegisch, G. (2018). Epigenetic Treatment Options in Urothelial Carcinoma. In: Schulz, W., Hoffmann, M., Niegisch, G. (eds) Urothelial Carcinoma. Methods in Molecular Biology, vol 1655. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7234-0_21

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  • DOI: https://doi.org/10.1007/978-1-4939-7234-0_21

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-7233-3

  • Online ISBN: 978-1-4939-7234-0

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