Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2016 May 24:8:57.
doi: 10.1186/s13148-016-0223-4. eCollection 2016.

Targeting histone methyltransferases and demethylases in clinical trials for cancer therapy

Ludovica Morera  1 , Michael Lübbert  2 , Manfred Jung  3
Affiliations
Review

Targeting histone methyltransferases and demethylases in clinical trials for cancer therapy

Ludovica Morera et al. Clin Epigenetics. .

Abstract

The term epigenetics is defined as heritable changes in gene expression that are not due to alterations of the DNA sequence. In the last years, it has become more and more evident that dysregulated epigenetic regulatory processes have a central role in cancer onset and progression. In contrast to DNA mutations, epigenetic modifications are reversible and, hence, suitable for pharmacological interventions. Reversible histone methylation is an important process within epigenetic regulation, and the investigation of its role in cancer has led to the identification of lysine methyltransferases and demethylases as promising targets for new anticancer drugs. In this review, we describe those enzymes and their inhibitors that have already reached the first stages of clinical trials in cancer therapy, namely the histone methyltransferases DOT1L and EZH2 as well as the demethylase LSD1.

Keywords: Clinical trial; Demethylase inhibitors; Epigenetics; Histone demethylase; Histone methyltransferase; Histone modifications; Lysine methylation; Methylome; Methyltransferase inhibitors.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Nucleosome structure and principal modification sites on H3, H4, and DNA. The reported writers, erasers, and readers for these modifications are also depicted
Fig. 2
Fig. 2
a Schematic view of DOT1L principal domains. b Structures of the methyl donor SAM, its enzymatic product SAH and of two DOT1L inhibitors. The SAM-like shared moiety is highlighted in bold
Fig. 3
Fig. 3
a Schematic view of EZH2 principal domains. b Structures of EZH2 inhibitors
Fig. 4
Fig. 4
a Schematic view of LSD1 principal domains. b Structures of the unselective LSD1/MAO inhibitor tranylcypromine (TCP), the selective LSD1 inhibitors from Oryzon and GSK and the dual HDAC/LSD1 inhibitor 4SC-202
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Kouzarides T. Chromatin modifications and their function. Cell. 2007;128:693–705. doi: 10.1016/j.cell.2007.02.005. - DOI - PubMed
    1. Rothbart SB, Strahl BD. Interpreting the language of histone and DNA modifications. BBA-Gene Regul Mech. 1839;2014:627–43. - PMC - PubMed
    1. Koh KP, Rao A. DNA methylation and methylcytosine oxidation in cell fate decisions. Curr Opin Cell Biol. 2013;25:152–61. doi: 10.1016/j.ceb.2013.02.014. - DOI - PMC - PubMed
    1. Biterge B, Schneider R. Histone variants: key players of chromatin. Cell Tissue Res. 2014;356:457–66. doi: 10.1007/s00441-014-1862-4. - DOI - PubMed
    1. Hargreaves DC, Crabtree GR. ATP-dependent chromatin remodeling: genetics, genomics and mechanisms. Cell Res. 2011;21:396–420. doi: 10.1038/cr.2011.32. - DOI - PMC - PubMed

Publication types

MeSH terms

LinkOut - more resources