Histone lysine methylation is widely recognized as part of the cell’s repertoire to alter chromatin structure, and thus to regulate processes that require access to DNA, including the regulation of transcription, DNA damage response and replication. Several protein families of lysine methyltransferases (KMTs), methyl-lysine demethylases (KDMs) and methyl-lysine specific chromatin binders, controlling placement, removal and recognition of histone lysine methylation marks were identified as transcriptional co-regulators to allow for dynamic changes in gene expression in response to a variety of stimuli.<br/><br/>Genomic and transcriptomic sequencing campaigns have revealed that KMTs, KDMs and methyl-lysine binders are frequently dysregulated in cancer, suggesting that cancer cells utilize manipulation of histone lysine methylation patterns as a means to tweak gene expression programs to gain a growth advantage. Multiple KMTs and KDMs have been identified as candidate oncogenic drivers in recent years. Small molecule KMT and KDM inhibitors constitute an attractive therapeutic approach to alter aberrant chromatin states and gene expression programs that cancer cells are dependent on. The discovery of KMT and KDM inhibitors, their application in various oncology contexts, as well as mechanistic consequences of target inhibition will be discussed.

Targeting histone lysine methylation regulatory pathways in cancer

253rd National Meeting (2017)

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