TitleEnhancer of zeste homolog 2 (EZH2) inhibitors.
Publication TypeJournal Article
Year of Publication2018
AuthorsGulati, Nitya, B├ęguelin Wendy, and Giulino-Roth Lisa
JournalLeuk Lymphoma
Volume59
Issue7
Pagination1574-1585
Date Published2018 Jul
ISSN1029-2403
KeywordsAnimals, Antineoplastic Agents, Antineoplastic Combined Chemotherapy Protocols, Clinical Trials as Topic, Combined Modality Therapy, Drug Evaluation, Preclinical, Drug Resistance, Neoplasm, Enhancer of Zeste Homolog 2 Protein, Enzyme Inhibitors, Epigenesis, Genetic, Humans, Lymphoma, B-Cell, Molecular Targeted Therapy, Treatment Outcome
Abstract

<p>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.</p>

DOI10.1080/10428194.2018.1430795
Alternate JournalLeuk Lymphoma
PubMed ID29473431
PubMed Central IDPMC6659997
Grant ListK08 CA219473 / CA / NCI NIH HHS / United States
P30 CA008748 / CA / NCI NIH HHS / United States