Our results reveal an epigenetic block to differentiation in CC-ICs and demonstrate the potential for epigenetic differentiation therapy of a solid tumour through EZH2 inhibition.
Clinical research evaluating BET and EZH2 inhibitors is still at an early stage; however, both classes of drugs have demonstrated activity among different hematologic malignancies and solid tumors.
In preclinical models encompassing a broad spectrum of EZH2-aberrant solid tumors, a combination of EZH2 and BRD4 inhibitors, or a triple-combination including MAPK inhibition display robust efficacy with very tolerable toxicity.
Three EZH2 inhibitors: tazemetostat (EPZ-6438), GSK2816126 and CPI-1205 have moved into phase I/phase II clinical trials in patients with non-Hodgkin lymphoma and genetically defined solid tumors.
These emerging data suggest that EZH2 inhibitors represent a very promising class of drugs, which will probably have a major impact on improving outcome and reducing toxicity for patients with indolent and aggressive B-cell lymphomas and other specific solid tumors.
In contrast, we recently showed that EZH2 is dispensable for solid tumor development and that its elevated expression reflects the abnormally high proliferation rate of cancer cells.
Although benign epithelial cells express very low levels of EZH2, increased levels of EZH2 have been observed in aggressive solid tumors such as those of the prostate, breast and bladder.