Abstract
Prostate cancer affects an increasing number of men worldwide and is a leading cause of cancer-associated deaths. Beside genetic mutations, many epigenetic alterations including DNA and histone modifications have been identified in clinical prostate tumor samples. They have been linked to aberrant activity of enzymes and reader proteins involved in these epigenetic processes, leading to the search for dedicated inhibitory compounds. In the wake of encouraging anti-tumor efficacy results in preclinical models, epigenetic modulators addressing different targets are now being tested in prostate cancer patients. In addition, the assessment of microRNAs as stratification biomarkers, and early clinical trials evaluating suppressor microRNAs as potential prostate cancer treatment are being discussed.
Highlights
Prostate adenocarcinoma is one of the most frequent male malignancies in developed countries and is a leading cause of cancer-related deaths
Findings on the role of DNA methylation and histone acetylation, and the subsequent discovery of bespoke DNA methyltransferases (DNMTs) and histone deacetylases (HDACs) inhibitors led to extensive clinical testing
Multiple side-effects leading to lack of therapeutic window have been reported in many instances, implying that more selective drugs and stratification strategies to identify prostate cancer subgroups will be essential in defining the patient subpopulation most likely to respond to such treatments
Summary
Prostate adenocarcinoma is one of the most frequent male malignancies in developed countries and is a leading cause of cancer-related deaths. This was evidenced by extensive genomic profiling analyses performed on primary tumors [8] and on metastatic samples [2] These studies confirmed the essential role of the AR axis in early and late stages of the disease, vindicating ongoing efforts towards the identification of more efficacious AR antagonists and androgen synthesis inhibitors [9,10]. Signaling downstream of AR activation is closely regulated by epigenetic modifications, suggesting that interfering with local chromatin modulation may represent a promising novel strategy to block androgen-mediated gene transcription This area has attracted much attention due to the anticipated reversibility of epigenetic alterations and the recent identification of potent and selective inhibitors of epigenetic tumor drivers [20,21]. Epigenetic Events in Prostate Cancer and Preclinical Efficacy of Inhibitors of Epigenetic Targets
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
