Enhancer of zeste homolog 2 (EZH2) inhibitors.
Nitya GulatiWendy BéguelinLisa Giulino-RothPublished in: Leukemia & lymphoma (2018)
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.
Keyphrases
- small molecule
- diffuse large b cell lymphoma
- clinical trial
- phase ii
- long noncoding rna
- long non coding rna
- wild type
- epstein barr virus
- open label
- transcription factor
- signaling pathway
- risk assessment
- gene expression
- big data
- machine learning
- cell proliferation
- current status
- climate change
- phase iii
- human health
- study protocol