ArticleOncotarget2015
Combining BET and HDAC inhibitors synergistically induces apoptosis of melanoma and suppresses AKT and YAP signaling.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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.
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Who cites it
42 citing papers in PubMed, 86 citations in OpenAlex.
- Current Research in Polypharmacology for Cancer Treatment Using Dual-Target Histone Deacetylase Inhibitors.International journal of molecular sciences · 2026Review
- Epigenetic reprogramming as the nexus of cancer stemness and therapy resistance: implications for biomarker discovery.Discover oncology · 2025Review
- Development and Validation of an HPLC-MS/MS Method for Determining I-BET151 in Rat Plasma and Its application to Pharmacokinetic Studies.Drug design, development and therapy · 2025Article
- Histone deacetylases in the regulation of cell death and survival mechanisms in resistant BRAF-mutant cancers.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Review
- Development of Potent Dual BET/HDAC Inhibitors via Pharmacophore Merging and Structure-Guided Optimization.ACS chemical biology · 2024Article
- BET Bromodomain Inhibitors: Novel Design Strategies and Therapeutic Applications.Molecules (Basel, Switzerland) · 2023Review
- SWI/SNF complex, promising target in melanoma therapy: Snapshot view.Frontiers in medicine · 2023Review
- Dual HDAC/BRD4 Inhibitors Relieves Neuropathic Pain by Attenuating Inflammatory Response in Microglia After Spared Nerve Injury.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Article
- Report of the First International Symposium on NUT Carcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- Drugging the Epigenome: Overcoming Resistance to Targeted and Immunotherapies in Melanoma.JID innovations : skin science from molecules to population health · 2022Review
- TEAD4 as an Oncogene and a Mitochondrial Modulator.Frontiers in cell and developmental biology · 2022Review
- Enhancing Therapeutic Approaches for Melanoma Patients Targeting Epigenetic Modifiers.Cancers · 2021Review
- BET Proteins as Attractive Targets for Cancer Therapeutics.International journal of molecular sciences · 2021Review
- Interrogating Epigenome toward Personalized Approach in Cutaneous Melanoma.Journal of personalized medicine · 2021Review
- Epigenetic Treatment of Urothelial Carcinoma Cells Sensitizes to Cisplatin Chemotherapy and PARP Inhibitor Treatment.Cancers · 2021Article
- Dura cells in the etiopathogenesis of Crouzon syndrome: the effects of FGFR2 mutations in the dura cells on the proliferation of osteoblasts through the hippo/YAP mediated transcriptional regulation pathway.American journal of translational research · 2021Article
- Anticancer Effects of I-BET151, an Inhibitor of Bromodomain and Extra-Terminal Domain Proteins.Frontiers in oncology · 2021Review
- Review
- A Synergistic Anticancer FAK and HDAC Inhibitor Combination Discovered by a Novel Chemical-Genetic High-Content Phenotypic Screen.Molecular cancer therapeutics · 2020Article
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
Abstract
Histone acetylation marks have an important role in controlling gene expression and are removed by histone deacetylases (HDACs). These marks are read by bromodomain and extra-terminal (BET) proteins and novel inhibitiors of these proteins are currently in clinical development. Inhibitors of HDAC and BET proteins have individually been shown to cause apoptosis and reduce growth of melanoma cells. Here we show that combining the HDAC inhibitor LBH589 and BET inhibitor I-BET151 synergistically induce apoptosis of melanoma cells but not of melanocytes. Induction of apoptosis proceeded through the mitochondrial pathway, was caspase dependent and involved upregulation of the BH3 pro-apoptotic protein BIM. Analysis of signal pathways in melanoma cell lines resistant to BRAF inhibitors revealed that treatment with the combination strongly downregulated anti-apoptotic proteins and proteins in the AKT and Hippo/YAP signaling pathways. Xenograft studies showed that the combination of inhibitors was more effective than single drug treatment and confirmed upregulation of BIM and downregulation of XIAP as seen in vitro. These results support the combination of these two classes of epigenetic regulators in treatment of melanoma including those resistant to BRAF inhibitors.
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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.