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Karolak et al. J Cancer Metastasis Treat 2021;7:15 Journal of Cancer
DOI: 10.20517/2394-4722.2021.05
Metastasis and Treatment

Review Open Access

Targeting EZH2 for the treatment of soft tissue
sarcomas

2
1
1
Magdalena Karolak , Ian Tracy , Janet Shipley , Zoë S Walters 1
1
Translational Epigenomics Team, Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton SO16 6YD,
UK.
2
Sarcoma Molecular Pathology Team, Divisions of Molecular Pathology and Cancer Therapeutics, The Institute of Cancer
Research, London SM2 5NG, UK.
Correspondence to: Zoë S Walters, Translational Epigenomics Team, Cancer Sciences, Faculty of Medicine, University of
Southampton, Southampton SO16 6YD, UK. E-mail: z.s.walters@soton.ac.uk
How to cite this article: Karolak M, Tracy I, Shipley J, Walters ZS. Targeting EZH2 for the treatment of soft tissue sarcomas. J
Cancer Metastasis Treat 2021;7:15. https://dx.doi.org/10.20517/2394-4722.2021.05

Received: 7 Jan 2021 First Decision: 2 Feb 2021 Revised: 8 Feb 2021 Accepted: 25 Feb 2021 Available online: 26 Mar 2021

Academic Editor: Ian Judson Copy Editor: Yue-Yue Zhang Production Editor: Yue-Yue Zhang

Abstract
Soft tissue sarcomas (STS) are a heterogenous group of rare malignancies of mesenchymal origin, affecting both
children and adults. The majority of STS have a poor prognosis and advanced stage at the time of diagnosis.
Standard treatments for STS largely constitute tumour resection with chemotherapy and/or radiotherapy, and
there has been little significant advancement in the application of novel therapies for treatment of these tumours.
The current multimodal approach to therapy often leads to long-term side effects, and for some patients,
resistance to cytotoxic agents is associated with local recurrence and/or metastasis. There is, therefore, a need for
novel therapeutic strategies for the treatment of STS. Recent advances in epigenetics have implicated the histone
methyltransferase, EZH2, in the development and progression of diseases such as breast cancer, lymphoma and
more recently STS. Here we will review the current literature for EZH2 in STS, including high expression of EZH2 in
STS and correlation of this with specific features of malignancy (metastasis, histological grade, and prognosis). The
effects of targeting EZH2 using RNA interference and small molecule inhibitors will also be reviewed and the
potential for the use of EZH2 inhibition in therapeutic strategies for STS patients will be discussed.

Keywords: EZH2, epigenetics, therapy

© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing,
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