Despite the potential of targeted epigenetic therapies, most cancers do not respond to current epigenetic drugs. The polycomb repressive complex EZH2 inhibitor tazemetostat was recently approved for the treatment of SMARCB1-deficient epithelioid sarcomas, based on the functional antagonism between PRC2 and SMARCB1. Through the analysis of tumors of patients treated with tazemetostat, we recently defined key principles of their response and resistance to EZH2 epigenetic therapy. Here, using tr...