Finding an easy way to harmonize: a review of advances in clinical research and combination strategies of EZH2 inhibitors

Enhancer of zeste homolog 2 inhibitors (EZH2i) have garnered increased attention owing to their anticancer activity by targeting EZH2, a well-known cancer-promoting factor. However, some lymphomas are resistant to EZH2i, and EZH2i treatment alone is ineffective in case of EZH2-overexpressing solid tumors. The anti-cancer efficacy of EZH2i may be improved through safe and effective combinations of these drugs with other treatment modalities. Preclinical evidence indicates that combining EZH2i with other therapies, such as immunotherapy, chemotherapy, targeted therapy, and endocrine therapy, has complementary or synergistic antitumor effects. Therefore, elucidating the underlying mechanisms of the individual constituents of the combination therapies is fundamental for their clinical application. In this review, we have summarized notable clinical trials and preclinical studies using EZH2i, their progress, and combinations of EZH2i with different therapeutic modalities, aiming to provide new insights for tumor treatment.

Automated summary

EZH2 inhibitors have shown anticancer activity by targeting EZH2, but resistance in some lymphomas and solid tumors calls for combination with other treatment modalities to enhance efficacy. Combining EZH2 inhibitors with therapies such as immunotherapy, chemotherapy, targeted therapy, and endocrine therapy has demonstrated complementary or synergistic antitumor effects.