ArticleGenes & development2018
Genetic modifiers of the BRD4-NUT dependency of NUT midline carcinoma uncovers a synergism between BETis and CDK4/6is.
Article in Genes & development, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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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
50 citing papers in PubMed, 62 citations in OpenAlex.
- International guidelines on the diagnosis and treatment of NUT carcinoma.Innovation (Cambridge (Mass.)) · 2026Review
- Primary Pulmonary NUT Carcinoma: A Case Illustration of Therapeutic Challenges and Review of Emerging Targeted Therapies.Case reports in oncological medicine · 2026Article
- BET Bromodomain Inhibition Reverses CDK4/6 Inhibitor Resistance in Estrogen Receptor-Positive Breast Cancer via Induction of miR-34a-5p.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Hiding in plain sight: NUT carcinoma is an unrecognized subtype of squamous cell carcinoma of the lungs and head and neck.Nature reviews. Clinical oncology · 2025Review
- CDK4/6 inhibitors in breast cancer therapy: mechanisms of drug resistance and strategies for treatment.Frontiers in pharmacology · 2025Review
- Pulmonary NUT carcinoma, an elusive and refractory entity, shows transient response to chemotherapeutics and PD-1 inhibitor: a case report and literature review.Frontiers in immunology · 2025Review
- [Research Progress on Pathogenesis and Treatment of NUT Carcinoma].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2024Review
- Multimodal Therapy Approaches for NUT Carcinoma by Dual Combination of Oncolytic VirusViruses · 2024Article
- Initial Chemotherapy for Locally Advanced and Metastatic NUT Carcinoma.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2024Article
- Sustained Clinical Response to Immunotherapy Followed by BET Inhibitor in a Patient with Unresectable Sinonasal NUT Carcinoma.Journal of immunotherapy and precision oncology · 2024Article
- Super-enhancers and the super-enhancer reader BRD4: tumorigenic factors and therapeutic targets.Cell death discovery · 2023Review
- The BRD4-NUT Fusion Alone Drives Malignant Transformation of NUT Carcinoma.Cancer research · 2023Article
- EZH2 Cooperates with BRD4-NUT to Drive NUT Carcinoma Growth by Silencing Key Tumor Suppressor Genes.Cancer research · 2023Article
- Prolonged Survival of NUT Midline Carcinoma and Current Approaches to Treatment.The oncologist · 2023Article
- EZH2 synergizes with BRD4-NUT to drive NUT carcinoma growth through silencing of key tumor suppressor genes.bioRxiv : the preprint server for biology · 2023Article
- Cell state-dependent chromatin targeting in NUT carcinoma.Genetics · 2023Article
- Revolutionizing DNA repair research and cancer therapy with CRISPR-Cas screens.Nature reviews. Molecular cell biology · 2023Review
- Cell state-dependent chromatin targeting in NUT carcinoma.bioRxiv : the preprint server for biology · 2023Article
- Epigenetic remodeling of the immune landscape in cancer: therapeutic hurdles and opportunities.Journal of biomedical science · 2023Review
- Combination of Ribociclib with BET-Bromodomain and PI3K/mTOR Inhibitors for Medulloblastoma Treatment In Vitro and In Vivo.Molecular cancer therapeutics · 2023Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Bromodomain and extraterminal (BET) domain inhibitors (BETis) show efficacy on NUT midline carcinoma (NMC). However, not all NMC patients respond, and responders eventually develop resistance and relapse. Using CRISPR and ORF expression screens, we systematically examined the ability of cancer drivers to mediate resistance of NMC to BETis and uncovered six general classes/pathways mediating resistance. Among these, we showed that RRAS2 attenuated the effect of JQ1 in part by sustaining ERK pathway function during BRD4 inhibition. Furthermore, overexpression of Kruppel-like factor 4 (KLF4), mediated BETi resistance in NMC cells through restoration of the E2F and MYC gene expression program. Finally, we found that expression of cyclin D1 or an oncogenic cyclin D3 mutant or RB1 loss protected NMC cells from BETi-induced cell cycle arrest. Consistent with these findings, cyclin-dependent kinase 4/6 (CDK4/6) inhibitors showed synergistic effects with BETis on NMC in vitro as well as in vivo, thereby establishing a potential two-drug therapy for NMC.
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