ArticleOncotarget2015
BRD4-targeted therapy induces Myc-independent cytotoxicity in Gnaq/11-mutatant uveal melanoma cells.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- Multiple neoplasms in patients with uveal melanoma: a systematic review.International ophthalmology · 2024Pooled it
- Novel gene therapy for drug-resistant melanoma: Synergistic combination of PTEN plasmid and BRD4 PROTAC-loaded lipid nanocarriers.Molecular therapy. Nucleic acids · 2024Article
- BET Bromodomain Inhibition Potentiates Ocular Melanoma Therapy by Inducing Cell Cycle Arrest.Investigative ophthalmology & visual science · 2024Article
- High-throughput chemogenetic drug screening reveals PKC-RhoA/PKN as a targetable signaling vulnerability in GNAQ-driven uveal melanoma.Cell reports. Medicine · 2023Article
- Article
- BAP1 loss augments sensitivity to BET inhibitors in cancer cells.Acta pharmacologica Sinica · 2022Article
- Review
- Metastatic disease to the liver: Locoregional therapy strategies and outcomes.World journal of clinical oncology · 2021Review
- The Latest on Uveal Melanoma Research and Clinical Trials: Updates from the Cure Ocular Melanoma (CURE OM) Science Meeting (2019).Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- Clinical Trials in Metastatic Uveal Melanoma: Current Status.Ocular oncology and pathology · 2020Review
- Novel Approaches to the Systemic Management of Uveal Melanoma.Current oncology reports · 2020Review
- Targeting Epigenetic Modifications in Uveal Melanoma.International journal of molecular sciences · 2020Review
- Mouse models of uveal melanoma: Strengths, weaknesses, and future directions.Pigment cell & melanoma research · 2020Review
- Bromodomain and extraterminal domain inhibitor enhances the antitumor effect of imatinib in gastrointestinal stromal tumours.Journal of cellular and molecular medicine · 2020Article
- Uveal melanoma: progress in molecular biology and therapeutics.Therapeutic advances in medical oncology · 2020Review
- Review
- Inhibition of NF-κB-Dependent Signaling Enhances Sensitivity and Overcomes Resistance to BET Inhibition in Uveal Melanoma.Cancer research · 2019Article
- The BET Bromodomain Inhibitor I-BET-151 Induces Structural and Functional Alterations of the Heart Mitochondria in Healthy Male Mice and Rats.International journal of molecular sciences · 2019Article
- Stromal fibroblast growth factor 2 reduces the efficacy of bromodomain inhibitors in uveal melanoma.EMBO molecular medicine · 2019Article
- Proceedings of the Association for Research in Vision and Ophthalmology and Champalimaud Foundation Ocular Oncogenesis and Oncology Conference.Translational vision science & technology · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Uveal melanoma (UM) is an aggressive intraocular malignancy with limited therapeutic options. Both primary and metastatic UM are characterized by oncogenic mutations in the G-protein alpha subunit q and 11. Furthermore, nearly 40% of UM has amplification of the chromosomal arm 8q and monosomy of chromosome 3, with consequent anomalies of MYC copy number. Chromatin regulators have become attractive targets for cancer therapy. In particular, the bromodomain and extra-terminal (BET) inhibitor JQ1 has shown selective inhibition of c-Myc expression with antiproliferative activity in hematopoietic and solid tumors. Here we provide evidence that JQ1 had cytotoxic activity in UM cell lines carrying Gnaq/11 mutations, while in cells without the mutations had little effects. Using microarray analysis, we identified a large subset of genes modulated by JQ1 involved in the regulation of cell cycle, apoptosis and DNA repair. Further analysis of selected genes determined that the concomitant silencing of Bcl-xL and Rad51 represented the minimal requirement to mimic the apoptotic effects of JQ1 in the mutant cells, independently of c-Myc. In addition, administration of JQ1 to mouse xenograft models of Gnaq-mutant UM resulted in significant inhibition of tumor growth.Collectively, our results define BRD4 targeting as a novel therapeutic intervention against UM with Gnaq/Gna11 mutations.
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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.