Abstract
During cancer development and progression, tumor cells undergo abnormal epigenetic modifications, including DNA methylation, histone deacetylation and nucleosome remodeling. Collectively, these aberrations promote genomic instability and lead to silencing of tumor-suppressor genes and reactivation of oncogenic retroviruses. Epigenetic modifications, therefore, provide exciting new avenues for prostate cancer research. Promoter hypermethylation is widespread during neoplastic transformation of prostate cells, which suggests that restoration of a 'normal' epigenome through treatment with inhibitors of the enzymes involved could be clinically beneficial. Global patterns of histone modifications are also being defined and have been associated with clinical and pathologic predictors of prostate cancer outcome. Although treatment for localized prostate cancer can be curative, the development of successful therapies for the management of castration-resistant metastatic disease is urgently needed. Reactivation of tumor-suppressor genes by demethylating agents and histone deacetylase inhibitors could be a potential treatment option for patients with advanced disease.
Key Points
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In addition to conventional mechanisms of gene inactivation, epigenetic changes—including gain and loss of DNA methylation and altered histone modifications—are considered a hallmark of human cancer
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Reversal of DNA methylation and histone modifications could potentially be therapeutic, as epigenetic modifications result in stable, heritable changes in gene expression without altering genetic sequences or gene function
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Prostate cancer is a model of 'epigenetic catastrophe', in which epigenetic changes that occur during the earliest stages of tumor initiation are maintained throughout disease progression
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Prostate cancer is an excellent candidate for chemoprevention using epigenetic modulators, owing to its late age of onset and slow growth
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The authors wish to acknowledge grant support from the Irish Cancer Society.
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A. S. Perry researched data for, and wrote, the article. R. W. G. Watson, M. Lawler and D. Hollywood reviewed and edited the article before submission.
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Perry, A., Watson, R., Lawler, M. et al. The epigenome as a therapeutic target in prostate cancer. Nat Rev Urol 7, 668–680 (2010). https://doi.org/10.1038/nrurol.2010.185
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DOI: https://doi.org/10.1038/nrurol.2010.185
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