Targeting histone methyltransferases and demethylases in clinical trials for cancer therapy

• Published in: Clinical epigenetics Vol. 8; no. 57; p. 57
• Main Authors: Morera, Ludovica, Lübbert, Michael, Jung, Manfred
• Format: Journal Article
• Language: English
• Published: Germany BioMed Central Ltd 24-05-2016; BioMed Central
• Subjects: Antimitotic agents; Antineoplastic agents; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Cancer; Care and treatment; Clinical trials; Clinical Trials as Topic; Enhancer of Zeste Homolog 2 Protein - antagonists & inhibitors; Enzyme Inhibitors - pharmacology; Enzyme Inhibitors - therapeutic use; Epigenesis, Genetic - drug effects; Epigenetic inheritance; Gene expression; Health aspects; Histone Demethylases - antagonists & inhibitors; Histone-Lysine N-Methyltransferase - antagonists & inhibitors; Histones; Humans; Lysine; Methylation; Methyltransferases; Methyltransferases - antagonists & inhibitors; Neoplasms - drug therapy; Neoplasms - enzymology; Neoplasms - genetics; Review; Lysine methylation; Epigenetics; Histone methyltransferase; Clinical trial; Histone demethylase; Histone modifications; Methylome; Methyltransferase inhibitors; Demethylase inhibitors
• ISSN: 1868-7075; 1868-7083; 1868-7083; 1868-7075
• DOI: 10.1186/s13148-016-0223-4

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.