BET Bromodomain Proteins as Cancer Therapeutic Targets
Open accessAbstract
Epigenetic regulators are emerging therapeutic targets in a wide variety of human cancers. BET bromodomain proteins have been identified as key regulators of oncogenic transcription factors including MYC; therefore, their inhibition might provide a way to block these "undruggable" targets. Several BET bromodomain inhibitors are in clinical development with promising preliminary findings. However, tumors acquire resistance to these agents in several different ways. In this review, we summarize the role that BET bromodomain proteins play in tumorigenesis as well as the molecular mechanisms underlying therapeutic responses and resistance to their inhibition with emphasis on BRD4 and breast cancer.
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Four top-ranking hit molecules from the screen, JQ1, I-BET151, I-BET762, and PFI-1, are inhibitors of BET family proteins.
“four top ranking hit molecules (JQ1, I-BET151, I-BET762, and PFI-1) turned out to be inhibitors of bromodomain and extra-terminal (BET) family proteins21,23”
From A BET family protein degrader provokes senolysis by targeting NHEJ and autophagy in senescent cells (2020) · cites this paper as [21]
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A BET family protein degrader provokes senolysis by targeting NHEJ and autophagy in senescent cells
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Targeting Bromodomain-Selective Inhibitors of BET Proteins in Drug Discovery and Development
Chen, J., Tang, P., Wang, Y., Wang, J., Yang, C., Li, Y., Yang, G., Wu, F., Zhang, J., & Ouyang, L. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c01835 · Cited by 62 · see citing works
- Authors
- Shu, S., & Polyak, K.
- Affiliations
- Brigham and Women's Hospital (US)
- ORCID
- Shu, Shaokun
- Venue
- Cold Spring Harbor Symposia on Quantitative Biology
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2016
- Volume
- 81
- Pages
- 123-129
- ISSN
- 0091-7451 (ISSN-L)
- 1943-4456
- OpenAlex
- W2570948885
- Cited by
- 72
- References
- 54
- Citations by year
- 2025: 1 · 2024: 5 · 2023: 7 · 2022: 6 · 2021: 16 · 2020: 15 · 2019: 6 · 2018: 7 · 2017: 9
- Type
- posted content
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- cc-by
- Locations
- Cold Spring Harbor Symposia on Quantitative Biology (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Susan G. Komen for the Cure
- Susan G. Komen
- National Institutes of Health
- National Cancer Institute (P50CA168504)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- BET proteins, bromodomain inhibitors, BRD4, c-Myc, epigenetic regulators, cancer therapy targets, drug resistance, breast cancer, carcinogenesis, undruggable targets, oncogenic transcription factor
- MeSH terms
- Bromodomain Containing Proteins, Animals, Humans, Neoplasms, Nuclear Proteins, Transcription Factors, Cell Cycle Proteins, Epigenesis, Genetic, Cell Proliferation
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