TitleEnhancer of zeste homolog 2 (EZH2) inhibitors.
Publication TypeJournal Article
Year of Publication2018
AuthorsGulati, Nitya, B├ęguelin Wendy, and Giulino-Roth Lisa
JournalLeuk Lymphoma
Date Published2018 Jul
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

<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>

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