KDM4
A Novel Target for Cancer Therapy
KDM4 is a family of histone demethylases that govern gene control by removing methyl groups from histones, and thereby regulating the accessibility of DNA to transcription factors. This can influence which genes are turned on or off as well a their level of expression.
The KDM4 family consists of four main isoforms (KDM4 A, B, C, and D). Functional redundancy and cross-activity has been observed across the KDM4 isoforms, therefore, inhibition of one isoform has been shown to to be ineffective. Pan-inhibition targeting multiple or all KDM4 isoforms is required to fully suppress KDM4 function.
In cancers, KDM4 has been shown to regulate critical signaling pathways involved in tumorigenesis such as cell proliferation, cancer stem cell maintenance, evasion of apoptosis, deficiency in DNA repair, metastasis, and stimulation of certain hormones.
KDM4 has been associated with driving cancers, as well as their resistance pathways, and is linked to aggressive disease and poor clinical outcomes.
KDM4 has emerged as a well-recognized anti-cancer target and Tachyon’s TACH101 is the only KDM4 inhibitor that is currently in clinical development. TACH101 is a potent, selective, pan-inhibitor of KDM4 proteins and is currently in a Phase 1 clinical trial for the treatment of advanced or metastatic cancers.