ArticleNature cancer2021
CDK4/6 inhibition reprograms the breast cancer enhancer landscape by stimulating AP-1 transcriptional activity.
Article in Nature cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 108 citations in OpenAlex.
- Palbociclib and endocrine therapy diminish adaptive anti-tumor immunity in early breast cancer: The NeoRHEA phase 2 study.Nature communications · 2025Trial
- VERONICA: Randomized Phase II Study of Fulvestrant and Venetoclax in ER-Positive Metastatic Breast Cancer Post-CDK4/6 Inhibitors - Efficacy, Safety, and Biomarker Results.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Trial
- Article
- CDK4/6 inhibition induces a senescence-associated secretory phenotype via delayed NF-κB activation.Life science alliance · 2026Article
- Integrative multi-omics profiling and machine learning reveal enhancer RNA signatures for early detection and prognostic stratification in breast cancer.NAR cancer · 2026Article
- Histone H4 lysine 20 tri-methylation safeguards breast cancer lineage fidelity and unfolded protein response.Nature communications · 2026Article
- Rewiring the Molecular Interplay of CDK4/6 Inhibitors in Lung Cancer: From Cell Cycle Control to Immune Microenvironment Remodeling.International journal of molecular sciences · 2026Review
- The Role of AP-1 in Cancer: Regulation, Tumor Microenvironment and Therapeutic Targeting.Biomolecules · 2026Review
- ESR1 mutations and CDK4/6 inhibitor choice shape clonal selection and adaptive cell states during acquired resistance.Genome medicine · 2026Article
- CDK4-selective inhibitor AU2-94 for the treatment of advanced and therapy-resistant prostate cancer.Journal of experimental & clinical cancer research : CR · 2026Article
- Cyclin-Dependent Kinases 4 and 6 Inhibitors: An Emerging Therapeutic Framework from Growth Suppression to Tumor Clearance.ACS pharmacology & translational science · 2026Review
- Targeting a super-enhancer induced aldehyde dehydrogenase metabolic loop mitigates CDK4/6 inhibitor resistance in estrogen receptor-positive cancers.Nature communications · 2026Article
- Charting the multilevel molecular response to palbociclib in ER-positive breast cancer.NAR cancer · 2026Article
- Predicting disease-specific histone modifications and functional effects of non-coding variants by leveraging DNA language models.Genome biology · 2026Article
- Age-independent and targetable transcription factor networks regulating CD8Cell reports · 2026Article
- The Dual Effects of CDK4/6 Inhibitors on Tumor Immunity.Cancers · 2025Review
- Alternate actions of CDK4/6 inhibitors beyond cell cycle blockade: unexplored roles in therapy resistance.Cancer metastasis reviews · 2025Review
- Article
- JNK pathway suppression mediates insensitivity to combination endocrine therapy and CDK4/6 inhibition in ER+ breast cancer.Journal of experimental & clinical cancer research : CR · 2025Article
- Emerging Mechanisms of Therapy Resistance in Metastatic ER+ Breast Cancer.Endocrinology · 2025Review
12 more citing papers are in PubMed but not listed here.
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Authors and funding
33 authors at 9 institutions in 4 countries.
Funding
Abstract
Pharmacologic inhibitors of cyclin-dependent kinases 4 and 6 (CDK4/6) were designed to induce cancer cell cycle arrest. Recent studies have suggested that these agents also exert other effects, influencing cancer cell immunogenicity, apoptotic responses, and differentiation. Using cell-based and mouse models of breast cancer together with clinical specimens, we show that CDK4/6 inhibitors induce remodeling of cancer cell chromatin characterized by widespread enhancer activation, and that this explains many of these effects. The newly activated enhancers include classical super-enhancers that drive luminal differentiation and apoptotic evasion, as well as a set of enhancers overlying endogenous retroviral elements that is enriched for proximity to interferon-driven genes. Mechanistically, CDK4/6 inhibition increases the level of several Activator Protein-1 (AP-1) transcription factor proteins, which are in turn implicated in the activity of many of the new enhancers. Our findings offer insights into CDK4/6 pathway biology and should inform the future development of CDK4/6 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.