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Review
. 2016 Sep 15:8:98.
doi: 10.1186/s13148-016-0264-8. eCollection 2016.

Epigenetic modulators as therapeutic targets in prostate cancer

Inês Graça  1 , Eva Pereira-Silva  2 , Rui Henrique  3 , Graham Packham  4 , Simon J Crabb  4 , Carmen Jerónimo  5
Affiliations
Review

Epigenetic modulators as therapeutic targets in prostate cancer

Inês Graça et al. Clin Epigenetics. .

Abstract

Prostate cancer is one of the most common non-cutaneous malignancies among men worldwide. Epigenetic aberrations, including changes in DNA methylation patterns and/or histone modifications, are key drivers of prostate carcinogenesis. These epigenetic defects might be due to deregulated function and/or expression of the epigenetic machinery, affecting the expression of several important genes. Remarkably, epigenetic modifications are reversible and numerous compounds that target the epigenetic enzymes and regulatory proteins were reported to be effective in cancer growth control. In fact, some of these drugs are already being tested in clinical trials. This review discusses the most important epigenetic alterations in prostate cancer, highlighting the role of epigenetic modulating compounds in pre-clinical and clinical trials as potential therapeutic agents for prostate cancer management.

Keywords: DNMTi; Histone modulators; Prostate cancer.

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Figures

Fig. 1
Fig. 1
Epigenetic alterations involved in PCa development and progression. Several epigenetic aberrations, as silencing of tumor suppressor genes by promoter hypermethylation, aberrant expression of histone modulating proteins, and DNA hypomethylation contribute not only to PCa onset but also to its progression to advanced and castration-resistant cancer
Fig. 2
Fig. 2
Writers, Erasers, and Readers. Epigenetic Writers (HATs, HDMs, and PRMTs) are responsible to establish epigenetic marks on amino acid residues of histone tails. Epigenetic Erasers (HDACs, KDMs and phosphatases) participate on the removal of the epigenetic marks. Epigenetic Readers (bromodomain, chromodomain and Tudor domain proteins) recognize and bind to a specific epigenetically modified mark
Fig. 3
Fig. 3
Epigenetic modifying drugs. This figure illustrates several epigenetic compounds classified accordingly to their respective epigenetic target that have been reported as having a role on PCa cell phenotype reversion either in pre-clinical or clinical assays
See this image and copyright information in PMC

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