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Evaluation of epigenetic biomarkers in prostate cancer patients before and after hormone ablation therapy

Objective

Prostate cancer is among the leading tumor types in men in the Western world. The heterogeneity of prostate cancer provides difficulties in tumor classification and decision-making for therapies. The establishment of new biomarkers is essential to develop individual treatments and facilitate tumor categorization. Therapies include hormone deprivation, which initially leads to tumor regression, but is associated with a high rate of recurrence. Both genetic and epigenetic alterations have been found in prostate cancer. Especially overexpression of the Polycomb protein EZH2 has been associated with aggressive tumors and bad prognosis. Additionally, DNA methylation of various genes including tumor suppressors, hormone receptors or cell cycle regulators has been described. Here we aim to investigate epigenetic patterns in human prostate cancer tissues before and after hormone ablation therapy, to evaluate novel biomarkers and to identify novel target genes of epigenetic mechanisms. We intend to monitor changes in epigenetic marks such as DNA methylation and Polycomb protein occupancy in prostate cancers before and after hormone deprivation. Furthermore, we aim to test our previous results obtained in prostate cancer cell lines to learn more about the clinical significance of epigenetic mechanisms in prostate cancer. The use of epigenetic drugs, such as DNA methyltransferase inhibitors and histone deacetylase inhibitors has been approved by the US food and drug administration for the treatment of specific hematological malignancies, and clinical trials have shown the beneficial effects for several tumor types. Thus, our study may elucidate novel molecular mechanisms of the disease and provide a rationale for the application of epigenetic drugs to target prostate cancer.

Call for proposal

FP7-PEOPLE-IRG-2008
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Funding Scheme

MC-IRG - International Re-integration Grants (IRG)

Coordinator

MEDIZINISCHE UNIVERSITAET WIEN
Address
Spitalgasse 23
1090 Wien
Austria
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 75 000
Administrative Contact
Dontscho Kerjaschki (Prof.)