Combining EZH2 and HDAC inhibitors to target castration-resistant prostate cancers

by Jonathan B. Coulter, Hariharan Easwaran

Development of resistance in castration-resistant prostate cancer (CRPC) involves epigenetic pathways. A new study in PLOS Biology demonstrates that combined therapy targeting enhancer of zeste homolog 2 (EZH2) and histone deacetylases (HDACs) may sensitize CRPC to both epigenetic and standard therapies. Development of resistance in castration-resistant prostate cancer (CRPC) involves epigenetic pathways involving EZH2 and HDACs. This Primer explores a PLOS Biology study showing that combined epigenetic therapy targeting these enzymes can activate cellular stress pathways, which may sensitize CRPC to both epigenetic and standard therapies.