Histone lysine demethylases as targets for anticancer therapy.
It has recently been demonstrated that the genes controlling the epigenetic programmes that are required for maintaining chromatin structure and cell identity include genes that drive human cancer. This observation has led to an increased awareness of chromatin-associated proteins as potentially interesting drug targets. The successful introduction of DNA methylation and histone deacetylase (HDAC) inhibitors for the treatment of specific subtypes of cancer has paved the way for the use of epigenetic therapy. Here, we highlight key biological findings demonstrating the roles of members of the histone lysine demethylase class of enzymes in the development of cancers, discuss the potential and challenges of therapeutically targeting them, and highlight emerging small-molecule inhibitors of these enzymes.
1] Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen, Denmark. [2] Centre for Epigenetics, University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen, Denmark. [3].
Jonas W
JW
Højfeldt
Karl
K
Agger
Kristian
K
Helin
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D016503:Drug Delivery Systems / Q000379:methods*; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage* / Q000737:chemistry; D056466:Histone Demethylases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology
D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D056466:Histone Demethylases