Enhancer of zeste homolog 2 (EZH2) inhibitors

Abstract

Dysregulation of the histone methyltransferase EZH2 plays a critical role in the development of a variety of malignancies including B-cell lymphomas. As a result, a series of small molecule inhibitors of EZH2 have been developed and studied in the pre-clinical setting. Three EZH2 inhibitors: tazemetostat (EPZ-6438), GSK2816126 and CPI-1205 have moved into phase I/phase II clinical trials in patients with non-Hodgkin lymphoma and genetically defined solid tumors. Early data from the tazemetostat trials indicate an acceptable safety profile and early signs of activity in diffuse large B-cell lymphoma and follicular lymphoma, including patients with EZH2 wild-type and mutant tumors. In this review, we present the rationale, key pre-clinical and early clinical findings of small molecule EZH2 inhibitors for use in lymphoma as well as future challenges and potential opportunities for combination therapies.

Keywords:

• Epigenetic
• non-Hodgkin lymphoma
• EZH2 inhibitors

Acknowledgements

NG received research support from St. Baldrick’s Foundation. LGR received research support from NCI (K08 CA219473), St. Baldrick’s Foundation, and Hyundai Hope on Wheels.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article online at https://doi.org/10.1080/10428194.2018.1430795.

Additional information

Funding

This work was supported by National Institutes of Health; Unravel Pediatric Cancer and Nitya Gulati was supported by St. Baldrick’s Foundation Fellowship [522077].