ArticleScientific reports2015
BET inhibitors induce apoptosis through a MYC independent mechanism and synergise with CDK inhibitors to kill osteosarcoma cells.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 118 citations in OpenAlex.
- Phase II trial of CDK4/6 inhibitor palbociclib in advanced sarcoma based on mRNA expression of CDK4/ CDKN2A.Signal transduction and targeted therapy · 2023Trial
- Targeting pre-existing club-like cells in prostate cancer potentiates androgen deprivation therapy.EMBO molecular medicine · 2026Article
- Therapeutic Targeting of BET Proteins in Sarcoma.Molecular cancer therapeutics · 2025Review
- MYC in cancer: from undruggable target to clinical trials.Nature reviews. Drug discovery · 2025Review
- FOSL1 is a key regulator of a super-enhancer driving TCOF1 expression in triple-negative breast cancer.Epigenetics & chromatin · 2024Article
- Liver cancer development driven by the AP-1/c-Jun~Fra-2 dimer through c-Myc.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Investigation of the impact of bromodomain inhibition on cytoskeleton stability and contraction.Cell communication and signaling : CCS · 2024Article
- 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
- The BRD4-SRPK2-SRSF2 signal modulates the splicing efficiency of ACSL3 pre-mRNA and influences erastin-induced ferroptosis in osteosarcoma cells.Cell death & disease · 2023Article
- PROTAC-Based Protein Degradation as a Promising Strategy for Targeted Therapy in Sarcomas.International journal of molecular sciences · 2023Review
- Investigation of the impact of bromodomain inhibition on cytoskeleton stability and contraction.bioRxiv : the preprint server for biology · 2023Article
- UTX inactivation in germinal center B cells promotes the development of multiple myeloma with extramedullary disease.Leukemia · 2023Article
- Targeting BET Proteins Downregulates miR-33a To Promote Synergy with PIM Inhibitors in CMML.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- BET Bromodomain Inhibitors: Novel Design Strategies and Therapeutic Applications.Molecules (Basel, Switzerland) · 2023Review
- NSMCE2, a novel super-enhancer-regulated gene, is linked to poor prognosis and therapy resistance in breast cancer.BMC cancer · 2022Article
- Report of the First International Symposium on NUT Carcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- The Fra-1/AP-1 Oncoprotein: From the "Undruggable" Transcription Factor to Therapeutic Targeting.Cancers · 2022Review
- Bromodomain 4 inhibition leads to MYCN downregulation in Wilms tumor.Pediatric blood & cancer · 2022Article
- The novel BET degrader, QCA570, is highly active against the growth of human NSCLC cells and synergizes with osimertinib in suppressing osimertinib-resistant EGFR-mutant NSCLC cells.American journal of cancer research · 2022Article
- BET Proteins as Attractive Targets for Cancer Therapeutics.International journal of molecular sciences · 2021Review
14 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osteosarcoma (OS) survival rates have plateaued in part due to a lack of new therapeutic options. Here we demonstrate that bromodomain inhibitors (BETi), JQ1, I-BET151, I-BET762, exert potent anti-tumour activity against primary and established OS cell lines, mediated by inhibition of BRD4. Strikingly, unlike previous observations in long-term established human OS cell lines, the antiproliferative activity of JQ1 in primary OS cells was driven by the induction of apoptosis, not cell cycle arrest. In further contrast, JQ1 activity in OS was mediated independently of MYC downregulation. We identified that JQ1 suppresses the transcription factor FOSL1 by displacement of BRD4 from its locus. Loss of FOSL1 phenocopied the antiproliferative effects of JQ1, identifying FOSL1 suppression as a potential novel therapeutic approach for OS. As a monotherapy JQ1 demonstrated significant anti-tumour activity in vivo in an OS graft model. Further, combinatorial treatment approaches showed that JQ1 increased the sensitivity of OS cells to doxorubicin and induced potent synergistic activity when rationally combined with CDK inhibitors. The greater level of activity achieved with the combination of BETi with CDK inhibitors demonstrates the efficacy of this combination therapy. Taken together, our studies show that BET inhibitors are a promising new therapeutic for OS.
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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.