Review: Targeting EZH2 in neuroblastoma

•Enhancer of Zeste Homolog 2 (EZH2) is overexpressed in neuroblastoma.•EZH2 is a histone methyltransferase that represses gene transcription.•EZH2 regulates differentiation in neuroblastoma cells.•Inhibition of EZH2 is a promising therapeutic strategy for neuroblastoma. Neuroblastoma is one of the c...

Full description

Saved in:
Bibliographic Details
Published in:Cancer treatment reviews 2023-09, Vol.119, p.102600-102600, Article 102600
Main Authors: Gao, Jinhui, Fosbrook, Claire, Gibson, Jane, Underwood, Timothy J., Gray, Juliet C., Walters, Zoë S.
Format: Article
Language:English
Subjects:
Cell Line, Tumor
Child
Enhancer of Zeste Homolog 2 Protein - genetics
EZH2
Humans
MYCN
Neoplasm Recurrence, Local
Neuroblastoma
Neuroblastoma - genetics
Neuroblastoma - pathology
Neuroblastoma - therapy
Polycomb Repressive Complex 2
PRC2
Tazemetostat
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:•Enhancer of Zeste Homolog 2 (EZH2) is overexpressed in neuroblastoma.•EZH2 is a histone methyltransferase that represses gene transcription.•EZH2 regulates differentiation in neuroblastoma cells.•Inhibition of EZH2 is a promising therapeutic strategy for neuroblastoma. Neuroblastoma is one of the commonest extra-cranial pediatric tumors, and accounts for over 15% of all childhood cancer mortality. Risk stratification for children with neuroblastoma is based on age, stage, histology, and tumor cytogenetics. The majority of patients are considered to have high-risk neuroblastoma, for which the long-term survival is less than 50%. Current treatments combine surgical resection, chemotherapy, stem cell transplantation, radiotherapy, anti-GD2 based immunotherapy as well as the differentiating agent isotretinoin. Despite the intensive multimodal therapies applied, there are high relapse rates, and recurrent disease is often resistant to further therapy. Enhancer of Zeste Homolog 2 (EZH2), a catalytic subunit of Polycomb Repressive Complex 2 (PRC2), is a histone methyltransferase that represses transcription through trimethylation of lysine residue K27 on histone H3 (H3K27me3). It is responsible for epigenetic repression of transcription, making EZH2 an essential regulator for cell differentiation. Overexpression of EZH2 has been shown to promote tumorigenesis, cancer cell proliferation and prevent tumor cells from differentiating in a number of cancers. Therefore, research has been ongoing for the past decade, developing treatments that target EZH2 in neuroblastoma. This review summarises the role of EZH2 in neuroblastoma and evaluates the latest research findings on the therapeutic potential of targeting EZH2 in the treatment of neuroblastoma.
ISSN:0305-7372
1532-1967
DOI:10.1016/j.ctrv.2023.102600