ArticleNature communications2021
Clinical CDK4/6 inhibitors induce selective and immediate dissociation of p21 from cyclin D-CDK4 to inhibit CDK2.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
60 citing papers in PubMed, 101 citations in OpenAlex.
- Trial
- Models of Early Resistance to CDK4/6 Inhibitors Unveil Potential Therapeutic Treatment Sequencing.International journal of molecular sciences · 2025Trial
- Discovery of Bis-Thiourea Derivatives as Human DNA Topoisomerase IIα Inhibitors with Potent Anticancer Effects.ACS omega · 2026Article
- Article
- Multi-omic analysis of the liver-breast axis reveals key hepatic mediators of breast cancer progression.Science China. Life sciences · 2026Review
- Increased vulnerability of colorectal cancer models with high alkylation damage to NTHL1 inactivation.Scientific reports · 2026Article
- Beyond CDK4/6 Inhibition: Current Strategies in Hormone Receptor-Positive Metastatic Breast Cancer.Current treatment options in oncology · 2026Review
- Stigmasterol reverses rituximab resistance in diffuse large B-cell lymphoma via the MAPK1 signaling pathway.Translational cancer research · 2026Article
- HES1 oscillations are required for cell cycle reentry in oestrogen receptor-positive breast cancer cells.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- CDK2 inhibitor BLU-222 synergizes with CDK4/6 inhibitors in drug resistant breast cancers through p21/p27 induction.Nature communications · 2026Article
- G1/S arrest: a key mechanism of cellular aging and replicative senescence.Biogerontology · 2026Review
- Anti-Invasive and Apoptotic Effect of Eupatilin on YD-10B Human Oral Squamous Carcinoma Cells.Molecules (Basel, Switzerland) · 2025Article
- Kidneys on the Frontline: Nephrologists Tackling the Wilds of Acute Kidney Injury in Trauma Patients-From Pathophysiology to Early Biomarkers.Diagnostics (Basel, Switzerland) · 2025Review
- Sensitive, direct detection of non-coding off-target base editor unwinding and editing in primary cells.bioRxiv : the preprint server for biology · 2025Article
- Targeting CDK2 and other novel cell cycle targets for breast cancer therapy.Expert opinion on therapeutic targets · 2025Review
- Review
- Mitochondrial priming and response to BH3 mimetics in "one-two punch" senogenic-senolytic strategies.Cell death discovery · 2025Article
- Impact of G1 phase kinetics on the acquisition of stemness in cancer cells: the critical role of cyclin D.Molecular biology reports · 2025Review
- Cyclin-dependent protein kinases and cell cycle regulation in biology and disease.Signal transduction and targeted therapy · 2025Review
- Optimizing therapeutic approaches for HR+/HER2- advanced breast cancer: clinical perspectives on biomarkers and treatment strategies post-CDK4/6 inhibitor progression.Cancer drug resistance (Alhambra, Calif.) · 2025Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Since their discovery as drivers of proliferation, cyclin-dependent kinases (CDKs) have been considered therapeutic targets. Small molecule inhibitors of CDK4/6 are used and tested in clinical trials to treat multiple cancer types. Despite their clinical importance, little is known about how CDK4/6 inhibitors affect the stability of CDK4/6 complexes, which bind cyclins and inhibitory proteins such as p21. We develop an assay to monitor CDK complex stability inside the nucleus. Unexpectedly, treatment with CDK4/6 inhibitors-palbociclib, ribociclib, or abemaciclib-immediately dissociates p21 selectively from CDK4 but not CDK6 complexes. This effect mediates indirect inhibition of CDK2 activity by p21 but not p27 redistribution. Our work shows that CDK4/6 inhibitors have two roles: non-catalytic inhibition of CDK2 via p21 displacement from CDK4 complexes, and catalytic inhibition of CDK4/6 independent of p21. By broadening the non-catalytic displacement to p27 and CDK6 containing complexes, next-generation CDK4/6 inhibitors may have improved efficacy and overcome resistance mechanisms.
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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.