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Targeting Epigenetic Regulators for Cancer Therapy: Mechanisms and Advances in Clinical Trials

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Review

Targeting Epigenetic Regulators for Cancer Therapy: Mechanisms and Advances in Clinical Trials

Yuan Cheng et al. Signal Transduct Target Ther.

Abstract

Epigenetic alternations concern heritable yet reversible changes in histone or DNA modifications that regulate gene activity beyond the underlying sequence. Epigenetic dysregulation is often linked to human disease, notably cancer. With the development of various drugs targeting epigenetic regulators, epigenetic-targeted therapy has been applied in the treatment of hematological malignancies and has exhibited viable therapeutic potential for solid tumors in preclinical and clinical trials. In this review, we summarize the aberrant functions of enzymes in DNA methylation, histone acetylation and histone methylation during tumor progression and highlight the development of inhibitors of or drugs targeted at epigenetic enzymes.

Keywords: Cancer epidemiology; Drug development.

Conflict of interest statement

Conflict of interestThe authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1. Epigenetic regulation of DNA methylation, histone acetylation, and histone methylation.
Gene silencing in mammalian cells is usually caused by methylation of DNA CpG islands together with hypoacetylated and hypermethylated histones. The “writers” (DNMTs, HATs, and HMTs) and “erasers” (DNA-demethylating enzymes, HDACs, and KDMs) are enzymes responsible for transferring or removing chemical groups to or from DNA or histones; MBDs and other binding proteins are “readers” that recognize methyl-CpGs and modified histones. DNMTs, DNA methyltransferases; MBDs, methyl-CpG binding domain proteins; HATs, histone acetylases; HDACs, histone deacetylases; HMTs, histone methyltransferases; KDMs, histone-demethylating enzymes.
Fig. 2
Fig. 2. Epigenetic regulations in cancer.
Alterations in epigenetic modifications in cancer regulate various cellular responses, including cell proliferation, apoptosis, invasion, and senescence. Through DNA methylation, histone modification, chromatin remodeling, and noncoding RNA regulation, epigenetics play an important role in tumorigenesis. These main aspects of epigenetics present reversible effects on gene silencing and activation via epigenetic enzymes and related proteins. DNMTs, DNA methyltransferases; TETs, ten-eleven translocation enzymes; HATs, histone acetylases; HDACs, histone deacetylases; HMTs, histone methyltransferases; HDMs, histone-demethylating enzymes. MLL, biphenotypic (mixed lineage) leukemia.

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References

    1. Waddington CH. The epigenotype. Int J. Epidemiol. 2012;41:10–13. doi: 10.1093/ije/dyr184. - DOI - PubMed
    1. Holliday R. The inheritance of epigenetic defects. Science. 1987;238:163–170. doi: 10.1126/science.3310230. - DOI - PubMed
    1. Bird A. Perceptions of epigenetics. Nature. 2007;447:396–398. doi: 10.1038/nature05913. - DOI - PubMed
    1. Shen H, Laird PW. Interplay between the cancer genome and epigenome. Cell. 2013;153:38–55. doi: 10.1016/j.cell.2013.03.008. - DOI - PMC - PubMed
    1. Holliday R. A new theory of carcinogenesis. Br. J. Cancer. 1979;40:513–522. doi: 10.1038/bjc.1979.216. - DOI - PMC - PubMed

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