Abstract

Therapeutic Targeting of Epigenetic Machinery in Cancer: Novel Insights into Mechanism and Therapeutic Targets

WEE Zhen Ning Adrian, Postdoctoral Fellow, Genome Institute of Singapore

Although therapeutic targeting of EZH2 appears to be effective in lymphomas carrying EZH2 activating mutations, no viable therapeutic approaches for EZH2-overexpressing cancers have been developed. Using prostate cancer as a model, we have unraveled a novel mechanism underlying the repression of the IFN signaling pathway by EZH2. Interestingly, we found that pharmacological depletion of EZH2 could restore the IFN signaling pathway and delivered remarkable synergistic anti-tumor effect when combined with IFN treatment. Furthermore, we found that EZH2-mediated silencing of the IFN signaling occurs widely in human malignances whereby this combination could consistently induced robust apoptosis. Thus, we have identified a novel mechanism that may account for the defective IFN signaling observed in human cancers and patients carrying this deregulation may benefit from the combination of IFN and EZH2 targeted therapy.