Achieving clinical success with BET inhibitors as anti-cancer agents.
Journal
British journal of cancer
ISSN: 1532-1827
Titre abrégé: Br J Cancer
Pays: England
ID NLM: 0370635
Informations de publication
Date de publication:
04 2021
04 2021
Historique:
received:
08
06
2020
accepted:
11
02
2021
revised:
12
01
2021
pubmed:
17
3
2021
medline:
28
9
2021
entrez:
16
3
2021
Statut:
ppublish
Résumé
The transcriptional upregulation of oncogenes is a driving force behind the progression of many tumours. However, until a decade ago, the concept of 'switching off' these oncogenic pathways represented a formidable challenge. Research has revealed that members of the bromo- and extra-terminal domain (BET) motif family are key activators of oncogenic networks in a spectrum of cancers; their function depends on their recruitment to chromatin through two bromodomains (BD1 and BD2). The advent of potent inhibitors of BET proteins (BETi), which target either one or both bromodomains, represents an important step towards the goal of suppressing oncogenic networks within tumours. Here, we discuss the biology of BET proteins, advances in BETi design and highlight potential biomarkers predicting their activity. We also outline the logic of incorporating BETi into combination therapies to enhance its efficacy. We suggest that understanding mechanisms of activity, defining predictive biomarkers and identifying potent synergies represents a roadmap for clinical success using BETi.
Identifiants
pubmed: 33723398
doi: 10.1038/s41416-021-01321-0
pii: 10.1038/s41416-021-01321-0
pmc: PMC8076232
doi:
Substances chimiques
Antineoplastic Agents
0
Proteins
0
Transcription Factors
0
bromodomain and extra-terminal domain protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
1478-1490Subventions
Organisme : Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada)
ID : PJT-159759
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