Abstract
Enhancer of zeste homolog 2 (EZH2) is enzymatic catalytic subunit of polycomb repressive complex 2 (PRC2) that can alter downstream target genes expression by trimethylation of Lys-27 in histone 3 (H3K27me3). EZH2 could also regulate gene expression in ways besides H3K27me3. Functions of EZH2 in cells proliferation, apoptosis, and senescence have been identified. Its important roles in the pathophysiology of cancer are now widely concerned. Therefore, targeting EZH2 for cancer therapy is a hot research topic now and different types of EZH2 inhibitors have been developed. In this review, we summarize the structure and action modes of EZH2, focusing on up-to-date findings regarding the role of EZH2 in cancer initiation, progression, metastasis, metabolism, drug resistance, and immunity regulation. Furtherly, we highlight the advance of targeting EZH2 therapies in experiments and clinical studies.
Keywords:
Cancer; EZH2; EZH2 inhibitor; H3K27me3.
MeSH terms
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Adenosine / analogs & derivatives
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Adenosine / pharmacology
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Adenosine / therapeutic use
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Antineoplastic Agents / pharmacology
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Antineoplastic Agents / therapeutic use*
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Benzamides / pharmacology
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Benzamides / therapeutic use
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Biphenyl Compounds / pharmacology
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Biphenyl Compounds / therapeutic use
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Cell Cycle / physiology
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Cell Transformation, Neoplastic
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Clinical Trials as Topic
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Combined Modality Therapy
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Drug Resistance, Neoplasm / physiology
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Enhancer of Zeste Homolog 2 Protein / antagonists & inhibitors*
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Enhancer of Zeste Homolog 2 Protein / chemistry
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Enhancer of Zeste Homolog 2 Protein / physiology
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Epigenetic Repression / physiology*
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Histone Code / physiology*
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Histones / metabolism
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Humans
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Methylation
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Morpholines / pharmacology
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Morpholines / therapeutic use
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Multicenter Studies as Topic
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Neoplasm Metastasis / physiopathology
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Neoplasm Proteins / antagonists & inhibitors*
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Neoplasm Proteins / chemistry
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Neoplasm Proteins / physiology
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Neoplasms / drug therapy*
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Neoplasms / metabolism
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Polycomb Repressive Complex 2 / antagonists & inhibitors
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Pyridones / pharmacology
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Pyridones / therapeutic use
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Structure-Activity Relationship
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Transcriptional Activation / physiology
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Tumor Microenvironment / immunology
Substances
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Antineoplastic Agents
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Benzamides
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Biphenyl Compounds
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Histones
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Morpholines
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Neoplasm Proteins
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Pyridones
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3-deazaneplanocin
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EZH2 protein, human
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Enhancer of Zeste Homolog 2 Protein
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Polycomb Repressive Complex 2
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Adenosine
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tazemetostat