EZH2 inhibition by tazemetostat: mechanisms of action, safety and efficacy in relapsed/refractory follicular lymphoma.

ABSTRACT: Epigenetic alterations are major drivers of follicular lymphomagenesis, and these alterations are frequently caused by mutations in or upregulation of EZH2, a histone methyltransferase responsible for PRC2-mediated gene repression. EZH2 hyperactivation increases proliferation of B cells and prevents them from exiting the germinal center, favoring lymphomagenesis. The first FDA-approved EZH2 inhibitor is tazemetostat, which is orally available and targets both mutant and wild-type forms of the protein to induce cell cycle arrest and apoptosis of lymphoma cells in preclinical models. Phase II trials have shown objective response rates of 69% for patients with lymphoma-carrying EZH2 mutations and 35% for those with wild-type EZH2 without major toxicity, leading to tazemet

SUBMITTER: Julia E 

PROVIDER: S-EPMC9892962 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature