Combining EZH2 inhibitors with other therapies for solid tumors: more choices for better effects

Area of Science:

• Epigenetics
• Cancer Biology
• Pharmacology

Background:

• Enhancer of Zeste Homolog 2 (EZH2) is a key epigenetic regulator involved in histone methylation (H3K27).
• EZH2 dysregulation, including mutations and overexpression, is linked to tumor development and metastasis in both hematological and solid cancers.
• Current EZH2 inhibitors demonstrate efficacy in hematological malignancies but show limited success in solid tumors.

Purpose of the Study:

• To review and summarize combination strategies involving EZH2 inhibitors and other antitumor therapies.
• To elucidate the mechanisms underlying these combination therapies.
• To provide a reference for enhancing antitumor effects of EZH2 inhibitors in solid tumors.

Main Methods:

• Comprehensive literature review of clinical trials and preclinical studies.
• Analysis of combination strategies including immunotherapy, targeted therapy, chemotherapy, radiotherapy, hormone therapy, and epigenetic therapy.
• Examination of the mechanistic basis for combined therapeutic approaches.

Main Results:

• EZH2 inhibitors are being investigated in combination with diverse therapeutic modalities to overcome resistance in solid tumors.
• Combinations aim to synergize effects by targeting multiple oncogenic pathways or modulating the tumor microenvironment.
• Preclinical and clinical data highlight the potential of specific combination regimens.

Conclusions:

• Combination strategies are crucial for improving the therapeutic efficacy of EZH2 inhibitors in solid tumors.
• Further research into optimal combinations and their underlying mechanisms is warranted.
• This review serves as a guide for developing more effective cancer treatments targeting EZH2.