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Epigenetic Treatment Options in Urothelial Carcinoma

  • Maria Pinkerneil
  • Michèle J. Hoffmann
  • Günter NiegischEmail author
Protocol
Part of the Methods in Molecular Biology book series (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.

Key words

Urothelial carcinoma Targeted therapy Epigenetics Histone deacetylases Histone deacetylase inhibitors 

Notes

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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Copyright information

© Springer Science+Business Media LLC 2018

Authors and Affiliations

  • Maria Pinkerneil
    • 1
  • Michèle J. Hoffmann
    • 1
  • Günter Niegisch
    • 1
    Email author
  1. 1.Department of Urology, Medical FacultyHeinrich Heine University DüsseldorfDüsseldorfGermany

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