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Targeting BET bromodomain proteins in cancer: The example of lymphomas.
Journal article

Targeting BET bromodomain proteins in cancer: The example of lymphomas.

  • Spriano F Institute of Oncology Research, Faculty of Biomedical Sciences, USI, Bellinzona, Switzerland.
  • Stathis A Oncology Institute of Southern Switzerland, Bellinzona, Switzerland; Faculty of Biomedical Sciences, USI, Lugano, Switzerland.
  • Bertoni F Institute of Oncology Research, Faculty of Biomedical Sciences, USI, Bellinzona, Switzerland; Oncology Institute of Southern Switzerland, Bellinzona, Switzerland. Electronic address: francesco.bertoni@ior.usi.ch.
  • 2020-07-22
Published in:
  • Pharmacology & therapeutics. - 2020
BET
BRD2
BRD4
DNA damage response
JQ1
MYC
PROTAC
bromodomain
diffuse large B-cell lymphoma
epigenetics
immuno-oncology
lymphoma
English The Bromo- and Extra-Terminal domain (BET) family proteins act as "readers" of acetylated histones and they are important transcription regulators. BRD2, BRD3, BRD4 and BRDT, part of the BET family, are important in different tumors, where upregulation or translocation often occurs. The potential of targeting BET proteins as anti-cancer treatment originated with data obtained with a first series of compounds, and there are now several data supporting BET inhibition in both solid tumors and hematological malignancies. Despite very positive preclinical data in different tumor types, the clinical results have been so far moderate. Using lymphoma as an example to review the data produced in the laboratory and in the context of the early clinical trials, we discuss the modalities to make BET targeting more efficient both generating novel generation of compounds and by exploring the combination with small molecules affecting various signaling pathways, BCL2, or DNA damage response signaling, but also with additional epigenetic agents and with immunotherapy. We also discuss the mechanisms of resistance and the toxicity profiles so far reported.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://sonar.ch/global/documents/19895
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