Development of EZH2-based combination therapies and dual-target inhibitors for antitumor effects

EZH2, an epigenetic factor, plays a key role in tumor progression. Owing to its potential in cancer treatment, EZH2 inhibitors have become promising antitumor drugs. However, single-target inhibitors often face limitations such as drug resistance and side effects. With in-depth research on the combined application of epigenetics with other therapeutic approaches, combination therapies based on EZH2 inhibitors and dual-target inhibitors have attracted widespread attention due to their ability to improve efficacy, expand indications, and reduce adverse reactions. This article reviewed more than 80 reports on the combination of EZH2 with chemotherapy, radiotherapy, targeted therapy, and immunotherapy. Moreover, 9 dual-target inhibitors were summarized, namely EZH2/BRD4, EZH2/CDK9, EZH2/G9a, EZH2/HDAC, EZH2/HIF1α, EZH2/HSP90, EZH2/LSD1, and EZH2/PARP, EZH2/PD-L1. This review covered the latest research progress on the combination use of EZH2 inhibitors in combination therapy and dual-target inhibitors development, providing a reference for future optimization of combination therapy regimens and the development of new dual target inhibitors.