EZH2 is an epigenetic regulator that methylates lysine 27 on histone H3 (H3K27) and is closely related to the development and metastasis of tumors. It often shows gain-of-function mutations in hematological tumors, while it is often overexpressed in solid tumors. EZH2 inhibitors have shown good efficacy in hematological tumors in clinical trials but poor efficacy in solid tumors. Therefore, current research on EZH2 inhibitors has focused on exploring additional combination strategies in solid tumors. Herein we summarize the combinations and mechanisms of EZH2 inhibitors and other therapies, including immunotherapy, targeted therapy, chemotherapy, radiotherapy, hormone therapy and epigenetic therapy, both in clinical trials and preclinical studies, aiming to provide a reference for better antitumor effects.
Keywords: EZH2 inhibitors; chemotherapy; combination therapy; epigenetic therapy; immunotherapy; solid tumors; targeted therapy; tumor microenvironment.
EZH2 is a histone methyltransferase whose high expression is associated with a poor prognosis in various solid tumors. It is considered a target for cancer treatment. However, EZH2 inhibitors as monotherapy have shown disappointing efficacy in most solid tumors. This review summarizes the strategies of combining EZH2 inhibitors with other treatment regimens and their associated molecular mechanisms.