KDM4
A Critical Driver of Tumorigenesis and Novel Target for Cancer Therapy
The KDM4 family of histone demethylases (KDM4A, B, C, and D) are epigenetic regulators that have been shown to drive the tumorigenic process. KDM4 proteins govern the transcription of genes through their ability to demethylate histones (remove methyl groups from histones) and regulate chromatin structure. As a result, KDM4’s can regulate signaling pathways involved in tumorigenesis such as those promoting proliferation of cancer stem cells, evasion of apoptosis, deficiency in DNA repair, metastasis, and stimulation of certain hormones.
KDM4 overexpression and dysregulation have been associated with many cancer types, including breast, colorectal, esophageal, prostate, and lymphomas and is linked to aggressive disease and poor clinical outcomes.
In recent years, KDM4 has emerged as an important novel therapeutic target and Tachyon’s TACH101 is the only KDM4 inhibitor that is currently in clinical development. TACH101 is a potent, selective, first-in-class small molecule inhibitor of all KDM4 proteins and is currently in a Phase 1 clinical trial for the treatment of advanced or metastatic cancers.
KDM4 Publications
Chandhasin C, Dang V, Perabo F, Del Rosario JR, Chen YK, Filvaroff E, Stafford JA, Clarke MF. TACH101, a first-in-class pan-inhibitor of KDM4 histone demethylase. Anticancer Drugs. 2023 (in press).