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Epigenetik des Urothelkarzinoms

Pathogenese, verbesserte Diagnostik und neue Therapieansätze

Epigenetics in urothelial cancer

Pathogenesis, improving diagnostics and developing novel treatment options

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Zusammenfassung

Für das Urothelkarzinom der Harnblase werden dringend neue diagnostische Biomarker und neue therapeutische Angriffsziele als Alternative oder Ergänzung zur klassischen Chemotherapie benötigt. Epigenetische Veränderungen könnten dafür geeignet sein, da sie von zentraler Bedeutung für Entstehung und Progression von Urothelkarzinomen sind. Vermutlich tragen sie zu gestörten Differenzierungsprozessen und zu gesteigertem Metastasierungspotential bei. Solche Veränderungen betreffen DNA-Methylierung, Histonmodifikationen, Chromatinremodellierung, lange nichtkodierende RNA und microRNA. Faktoren, die an der Regulation von Histonmodifikationen oder Chromatinremodellierung beteiligt sind, sind beim Urothelkarzinom deutlich häufiger durch Mutationen inaktiviert als bei anderen Tumorarten. Daher wären solche Enzyme, nach gründlicher Untersuchung ihrer komplexen Wirkungsweisen, wahrscheinlich als neue therapeutische Angriffsziele geeignet. Veränderungen der DNA-Methylierung oder der microRNA-Expression kommen als diagnostische oder prognostische Biomarker in Frage, müssen aber durch umfassende Studien unter standardisierten Bedingungen validiert werden.

Abstract

Urothelial carcinoma of the bladder is a common tumor for which improvements in diagnostic markers and new therapy approaches, in addition to or combined with standard chemotherapy, are urgently required. Epigenetic alterations could provide both novel diagnostic markers and therapeutic targets as they are emerging as crucial factors in the development and progression of this tumor type, likely contributing to altered differentiation and metastatic potential. These alterations affect DNA methylation, histone modifications, chromatin remodeling, long noncoding RNAs, and microRNAs. Factors involved in histone modifications and chromatin remodeling appear to be particularly frequently inactivated by mutations. Thus, histone-modifying enzymes may represent good targets for rational new therapeutic approaches, although thorough investigation of their complex functions is a prerequisite. DNA methylation changes and altered miRNA expression provide promising biomarkers for diagnosis and prognosis that need further validation in comprehensive and well-standardized studies.

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Einhaltung ethischer Richtlinien

Interessenkonflikt. Unsere Arbeiten zum Thema werden durch die Deutsche Forschungsgemeinschaft, die Forschungskommission der Medizinischen Fakultät und die Bodossaki-Stiftung gefördert. G. Niegisch, M.J. Hoffmann, E.A. Koutsogiannouli und W.A. Schulz geben an, dass kein Interessenkonflikt besteht. Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.

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Authors and Affiliations

  1. Medizinische Fakultät, Urologische Klinik, Heinrich-Heine-Universität Düsseldorf, Moorenstraße 5, 40225, Düsseldorf, Deutschland

    G. Niegisch, M.J. Hoffmann, E.A. Koutsogiannouli & W.A. Schulz

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  1. G. Niegisch
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  2. M.J. Hoffmann
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  3. E.A. Koutsogiannouli
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  4. W.A. Schulz
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Correspondence to G. Niegisch.

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Niegisch, G., Hoffmann, M., Koutsogiannouli, E. et al. Epigenetik des Urothelkarzinoms. Urologe 54, 526–532 (2015). https://doi.org/10.1007/s00120-014-3756-1

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