EZH2 and cancer: Acquired resistance is usually because of multiple secondary mutations of EZH2, such as Y641F, C663Y, E720G, Y726F, Y111L, and Y661D.433,434,436,437 Combination therapy is thought as the most efficient strategy to improve the limited effectiveness of EZH2 inhibitors.438 For example, the approved drug tazemetostat is currently assessed clinically in several combined treatments for a variety of malignant tumors.