ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
Dual Inhibition of CDK4/6 and CDK7 Suppresses Triple-Negative Breast Cancer Progression via Epigenetic Modulation of SREBP1-Regulated Cholesterol Metabolism.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Article
- Metastasis of triple negative breast cancer is regulated by a targetable miR-342-E2F network.EMBO molecular medicine · 2026Article
- MNAT1 in gastrointestinal cancers: mechanistic insights and therapeutic strategies-a narrative review.Journal of gastrointestinal oncology · 2026Review
- Deciphering Hierarchical Transcriptional Control of Fatty Acid Metabolism in Megalobrama Amblycephala: Insights from Promoter Architecture, PPAR Synergy, and Network Biology.Marine biotechnology (New York, N.Y.) · 2026Article
- FOXN3 integrates the KU70/KU80/SREBP-1 complex to regulate lipid metabolism in non-alcoholic fatty liver disease.Nucleic acids research · 2026Article
- The pseudouridine synthase PUS7 is associated with stemness and represents a potential therapeutic target in triple-negative breast cancer cells.Scientific reports · 2026Article
- Lipid Metabolism and Breast Cancer Therapy: An Integrative Literature Review.Breast cancer (Dove Medical Press) · 2026Review
- Targeting Aurora A Kinase Enhance the CDK4/6 Inhibitor Sensitivity in HR+/HER2- Breast Cancer.Oncology research · 2026Article
- Alternate actions of CDK4/6 inhibitors beyond cell cycle blockade: unexplored roles in therapy resistance.Cancer metastasis reviews · 2025Review
- Gene Expression Profiles Modulated by Lipophilic Sea Buckthorn (Food science & nutrition · 2025Article
- Dual-Target Therapeutic Strategies in Triple-Negative Breast Cancer: Mechanistic Insights and Clinical Potential.Cancers · 2025Review
- Review
- Dual Inhibition of CDK4/6 and CDK7 Suppresses Triple-Negative Breast Cancer Progression via Epigenetic Modulation of SREBP1-Regulated Cholesterol Metabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
Corrections and comments
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Authors and funding
20 authors.
Funding
Abstract
Inhibitors targeting cyclin-dependent kinases 4 and 6 (CDK4/6) to block cell cycle progression have been effective in treating hormone receptor-positive breast cancer, but triple-negative breast cancer (TNBC) remains largely resistant, limiting their clinical applicability. The study reveals that transcription regulator cyclin-dependent kinase7 (CDK7) is a promising target to circumvent TNBC's inherent resistance to CDK4/6 inhibitors. Combining CDK4/6 and CDK7 inhibitors significantly enhances therapeutic effectiveness, leading to a marked decrease in cholesterol biosynthesis within cells. This effect is achieved through reduced activity of the transcription factor forkhead box M1 (FOXM1), which normally increases cholesterol production by inducing SREBF1 expression. Furthermore, this dual inhibition strategy attenuates the recruitment of sterol regulatory element binding transcription factor 1 (SREBP1) and p300 to genes essential for cholesterol synthesis, thus hindering tumor growth. This research is corroborated by an in-house cohort showing lower survival rates in TNBC patients with higher cholesterol production gene activity. This suggests a new treatment approach for TNBC by simultaneously targeting CDK4/6 and CDK7, warranting additional clinical trials.
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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 Socratic graph.