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Epigenetics of Indolent Lymphoma and How It Drives Novel Therapeutic Approaches—Focus on EZH2-Targeted Drugs

Authors
  • Longley, Jemma1
  • Johnson, Peter W. M.1
  • 1 University of Southampton, Southampton, UK , Southampton (United Kingdom)
Type
Published Article
Journal
Current Oncology Reports
Publisher
Springer-Verlag
Publication Date
May 03, 2021
Volume
23
Issue
7
Identifiers
DOI: 10.1007/s11912-021-01076-0
Source
Springer Nature
Keywords
License
Green

Abstract

Purpose of ReviewEpigenetic modifier gene mutations are common in patients with follicular lymphoma. Here we review the pathogenesis of these mutations and how they are targeted by epigenetic drugs including EZH2 inhibitors in both mutated and wild-type disease.Recent FindingsThe use of EZH2 inhibitor tazematostat in early phase clinical trials has proved encouraging in the treatment of follicular lymphoma harbouring an EZH2 mutation; however, responses are also seen in patients with wild-type disease which is partially explained by the off target effects of EZH2 inhibition on immune cells within the tumour microenvironment.SummaryFurther studies incorporating prospective molecular profiling are needed to allow stratification of patients at both diagnosis and relapse to further our understanding of how epigenetic modifier mutations evolve over time. The use of tazematostat in combination or upfront in patients with an EZH2 mutation remains unanswered; however, given durable responses, ease of oral administration, and tolerability, it is certainly an attractive option.

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