ArticleClinical cancer research : an official journal of the American Association for Cancer Research2019
Overcoming BET Inhibitor Resistance in Malignant Peripheral Nerve Sheath Tumors.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
- Review
- Targeting developmental vulnerabilities in childhood sarcomas.Cancer metastasis reviews · 2025Review
- Therapeutic Targeting of BET Proteins in Sarcoma.Molecular cancer therapeutics · 2025Review
- Past, Present, and Future Therapeutic Strategies for NF-1-Associated Tumors.Current oncology reports · 2024Review
- The multi-CDK inhibitor dinaciclib reverses bromo- and extra-terminal domain (BET) inhibitor resistance in acute myeloid leukemia via inhibition of Wnt/β-catenin signaling.Experimental hematology & oncology · 2024Article
- Targeting bromodomain-containing proteins: research advances of drug discovery.Molecular biomedicine · 2023Review
- The therapeutic potential of neurofibromin signaling pathways and binding partners.Communications biology · 2023Review
- Single-cell RNA sequencing of neurofibromas reveals a tumor microenvironment favorable for neural regeneration and immune suppression in a neurofibromatosis type 1 porcine model.Frontiers in oncology · 2023Article
- PRC2-Inactivating Mutations in Cancer Enhance Cytotoxic Response to DNMT1-Targeted Therapy via Enhanced Viral Mimicry.Cancer discovery · 2022Article
- Review
- Pharmacological Approaches in Neurofibromatosis Type 1-Associated Nervous System Tumors.Cancers · 2021Review
- Molecular mechanisms underpinning sarcomas and implications for current and future therapy.Signal transduction and targeted therapy · 2021Review
- Discovery and resistance mechanism of a selective CDK12 degrader.Nature chemical biology · 2021Article
- Epigenetic heterogeneity promotes acquired resistance to BET bromodomain inhibition in ovarian cancer.American journal of cancer research · 2021Article
- The epigenomics of sarcoma.Nature reviews. Cancer · 2020Review
- Diagnosis and management of malignant peripheral nerve sheath tumors: Current practice and future perspectives.Neuro-oncology advances · 2020Review
- Advanced pharmacological therapies for neurofibromatosis type 1-related tumors.Acta bio-medica : Atenei Parmensis · 2020Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
purposeBET bromodomain inhibitors have emerged as a promising therapy for numerous cancer types in preclinical studies, including neurofibromatosis type 1 (NF1)-associated malignant peripheral nerve sheath tumor (MPNST). However, potential mechanisms underlying resistance to these inhibitors in different cancers are not completely understood. In this study, we explore new strategy to overcome BET inhibitor resistance in MPNST.
resultsHere, we show that a malignant progression-associated increase in BRD4 protein levels corresponds to partial sensitivity to BET inhibition in MPNST. Strikingly, genetic depletion of BRD4 protein levels synergistically sensitized MPNST cells to diverse BET inhibitors in culture and
conclusionsCollectively, MPNST sensitivity to combination genetic and pharmacologic inhibition of BRD4 revealed the presence of a unique addiction to BRD4 in MPNST. Our discovery that a synthetic lethality exists between BET inhibition and reduced BRD4 protein levels nominates MPNST for the investigation of emerging therapeutic interventions such as proteolysis-targeting chimeras (PROTACs) that simultaneously target bromodomain activity and BET protein abundance.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.