Tazemetostat for the treatment of multiple types of hematological malignancies and solid tumors

Epigenetic alterations contributing to malignancy have become a more prominent field of investigation over the past several years, as several hallmarks of cancer are substantially altered by changes in the epigenome. Enhancer of zeste homologue 2 (EZH2), an enzyme involved in silencing the transcription of various genes, is overexpressed or mutated in multiple cancers and can lead to proliferation of dedifferentiated cells. Both gain-of-function and loss-of-function mutations have been noted in hematologic cancers, with gain-of-function mutations prevalent among non-Hodgkin lymphomas. Tazemetostat is a first-in-class EZH2 inhibitor developed to target this overexpression. Phase I trials have shown it is generally well tolerated and efficacious in solid tumors as well as hematological malignancies. Tazemetostat was approved by the U.S. Food and Drug Administration (FDA) for use in epithelioid sarcoma in January 2020 on the basis of the results of a recent phase II trial, but with several clinical trials ongoing, the use of tazemetostat for hematological malignancies is a promising avenue for treatment.