Title: Histone Methylation Modifiers in Medical Therapeutics
Abstract: Epigenetics has been recognized as a promising area for oncology target discovery because epigenetic regulatory processes are frequently dysregulated in cancer. Histone methylation constitutes an epigenetic regulatory pathway that allows for the effective regulation of gene expression. Histone methylation modifiers such as lysine methyltransferases and demethylases, protein arginine methyltransferases, and arginine deiminases function as coactivators and corepressors to maintain a cell's transcriptional program that defines its identity. In cancer cells, perturbation of this histone methylation network through gain of function mutations in individual histone methylation modifiers or through alterations in chromatin regulatory pathways that create functional dependencies on individual histone methylation modifiers alter cell fate and promote uncontrolled proliferation. The realization that cancer cells may depend on altered epigenetic regulatory cues that may be exploited therapeutically has propelled recent drug discovery initiatives. Potent and selective inhibitors of the histone methyltransferases EZH2 and DOT1L and the histone demethylase KDM1A have shown promise in preclinical oncology studies and have progressed to clinical development. In addition, a plethora of small molecules targeting other histones methylation modifiers is now available to explore disease biology. This chapter provides an overview of histone methylation modifiers and highlights key oncology targets in this space. The focus is set on medical therapeutics, and thus on the discovery of inhibitors of histone methylation modifiers and their potential value for the treatment of cancer.
Publication Year: 2016
Publication Date: 2016-01-01
Language: en
Type: book-chapter
Indexed In: ['crossref']
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Cited By Count: 1
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