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The Impact of Epigenetic Alterations on Diagnosis, Prediction, and Therapy of Prostate Cancer

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Patho-Epigenetics of Disease

Abstract

The current procedure for prostate cancer detection comprising PSA testing, digital rectal examination, and transrectal ultrasound-guided prostate biopsy is not considered satisfactory. On one hand, it may lead to overtreatment of clinically insignificant prostate cancers, but on the other hand, clinical prognostic parameters predict individual prognosis insufficiently with recurrent disease remaining commonly incurable. On that background, molecular analyses of prostate cancer pathogenesis aim to provide novel tools for early detection of aggressive cancers and prediction of individual prognosis as well as alternative treatment options. Epigenetic alterations are crucial in prostate cancer pathogenesis and may provide excellent biomarkers for these purposes. In this chapter, we discuss currently available and experimental diagnostic and prognostic biomarkers derived from epigenetic alterations in prostate cancer, which include changes in DNA methylation, histone modifications, and histone-modifying enzymes. The emphasis is on quality criteria such as sensitivity and specificity in their practical application to different types of samples and patient populations. We further review novel therapeutic compounds targeting epigenetic alterations, including histone deacetylase inhibitors and histone methyltransferase inhibitors, some of which are in clinical phase I and II trials, as well as histone demethylase inhibitors. The last part of this chapter gives a short perspective on future developments in the area of epigenetic markers and drugs, which include genome-wide analyses of epigenetic alterations and the emerging field of microRNAs.

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  1. Department of Urology, University Hospital, Duesseldorf, Germany

    Christian Arsov MD

  2. Department of Urology, Heinrich Heine University, Moorenstrasse 5, Duesseldorf, 40225, Germany

    Wolfgang Goering PhD & Wolfgang A. Schulz PhD

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  1. Microbiological Research Group, National Center for Epidemiology, Piheno u. 1, Budapest, 1529, Hungary

    Janos Minarovits

  2. University of Regensburg, Regensburg, 93053, Germany

    Hans Helmut Niller

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Arsov, C., Goering, W., Schulz, W.A. (2012). The Impact of Epigenetic Alterations on Diagnosis, Prediction, and Therapy of Prostate Cancer. In: Minarovits, J., Niller, H. (eds) Patho-Epigenetics of Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3345-3_6

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