ArticleScientific reports2015
GLI2-dependent c-MYC upregulation mediates resistance of pancreatic cancer cells to the BET bromodomain inhibitor JQ1.
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 57 papers.
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Who cites it
57 citing papers in PubMed, 90 citations in OpenAlex.
- A circular RNA overcomes acquired resistance to BET inhibitors by antagonizing IGF2BP2-mediated c-MYC translation in TNBC.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The role of fructose-1,6-bisphosphatase 1 on regulating the cancer progression and drug resistance.Discover oncology · 2025Review
- Peptide Inhibitor Targeting the Extraterminal Domain in BRD4 Potently Suppresses Breast Cancer BothJournal of medicinal chemistry · 2024Article
- Article
- BET Bromodomain Inhibitors: Novel Design Strategies and Therapeutic Applications.Molecules (Basel, Switzerland) · 2023Review
- Molecular Research in Pancreatic Cancer: Small Molecule Inhibitors, Their Mechanistic Pathways and Beyond.Current issues in molecular biology · 2023Review
- Target c-Myc to treat pancreatic cancer.Cancer biology & therapy · 2022Article
- Culture media composition influences patient-derived organoid ability to predict therapeutic responses in gastrointestinal cancers.JCI insight · 2022Article
- Epigenetic regulation of pancreatic adenocarcinoma in the era of cancer immunotherapy.Journal of gastroenterology · 2022Review
- Dual-target inhibitors of bromodomain and extra-terminal proteins in cancer: A review from medicinal chemistry perspectives.Medicinal research reviews · 2022Review
- BET Proteins as Attractive Targets for Cancer Therapeutics.International journal of molecular sciences · 2021Review
- Article
- Resistance to BET inhibitors in lung adenocarcinoma is mediated by casein kinase phosphorylation of BRD4.Oncogenesis · 2021Article
- Targeting Bromodomain and Extraterminal Proteins for Drug Discovery: From Current Progress to Technological Development.Journal of medicinal chemistry · 2021Review
- A Phase 1 study of RO6870810, a novel bromodomain and extra-terminal protein inhibitor, in patients with NUT carcinoma, other solid tumours, or diffuse large B-cell lymphoma.British journal of cancer · 2021Article
- Disruption of Cell-Cell Communication in Anaplastic Thyroid Cancer as an Immunotherapeutic Opportunity.Advances in experimental medicine and biology · 2021Article
- The emerging role of BET inhibitors in breast cancer.Breast (Edinburgh, Scotland) · 2020Review
- Article
- Small molecule inhibitors in pancreatic cancer.RSC medicinal chemistry · 2020Review
- The aberrant expression of ADAR1 promotes resistance to BET inhibitors in pancreatic cancer by stabilizing c-Myc.American journal of cancer research · 2020Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
JQ1 and I-BET151 are selective inhibitors of BET bromodomain proteins that have efficacy against a number of different cancers. Since the effectiveness of targeted therapies is often limited by development of resistance, we examined whether it was possible for cancer cells to develop resistance to the BET inhibitor JQ1. Here we show that pancreatic cancer cells developing resistance to JQ1 demonstrate cross-resistance to I-BET151 and insensitivity to BRD4 downregulation. The resistant cells maintain expression of c-MYC, increase expression of JQ1-target genes FOSL1 and HMGA2, and demonstrate evidence of epithelial-mesenchymal transition (EMT). However, reverting EMT fails to sensitize the resistant cells to JQ1 treatment. Importantly, the JQ1-resistant cells remain dependent on c-MYC that now becomes co-regulated by high levels of GLI2. Furthermore, downregulating GLI2 re-sensitizes the resistant cells to JQ1. Overall, these results identify a mechanism by which cancer cells develop resistance to BET 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.