The role of histone demethylases in cancer therapy

Reversible histone methylation has emerged in the last few years as an important mechanism of epigenetic regulation. Histone methyltransferases and demethylases have been identified as contributing factors in the development of several diseases, especially cancer. Therefore, they have been postulated to be new drug targets with high therapeutic potential. Here, we review histone demethylases with a special focus on their potential role in oncology drug discovery. We present an overview over the different classes of enzymes, their biochemistry, selected data on their role in physiology and already available inhibitors.

► Histone demethylation is a major factor of epigenetic regulation.
► It has been implicated in the pathogenesis of cancer in many studies.
► First inhibitors for the histone demethylases are available and have shown great promise for drug development.
►  Structural data on demethylases and enzyme–inhibitor complexes are available and may greatly aid in inhibitor optimization.