ArticleMolecular cell2023
CDK4/6 inhibitor-mediated cell overgrowth triggers osmotic and replication stress to promote senescence.
Article in Molecular cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
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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.
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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
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.
- A meta-analysis and systematic review of different cyclin-dependent kinase 4/6 inhibitors in breast cancer.Frontiers in oncology · 2025Pooled it
- Identification of a Conserved Temporal Molecular Response Signature to CDK4/6 Inhibition Through Multi-Omics Integration Across Cancer Cell Lines.International journal of molecular sciences · 2026Article
- Molecular Mechanisms and Molecular Subtype-Specific Responses to Paclitaxel in Breast Cancer Cells.Molecules (Basel, Switzerland) · 2026Article
- CDK4/6 Inhibitor-Induced Senescence in Cancer: Mechanisms and Therapeutic Implications.Cancers · 2026Review
- The evolving landscape of CDK inhibitor use in breast cancer therapy and beyond.Nature reviews. Drug discovery · 2026Review
- Cell size-dependent mRNA transcription drives proteome remodeling.Cell reports · 2026Article
- Catechin-Folate nano-niosomes from Osbeckia parvifolia Arn. induce apoptotic cell death in Ovarian cancer.Scientific reports · 2026Article
- Fatty acid synthesis therapy-induced senescence (FASTIS) in cancer cells.Cell death & disease · 2026Article
- Experimental evolution of cellular miniaturization reveals a putative mechanism for cell size evolution.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Cell size modulates ferroptosis susceptibility.eLife · 2026Article
- TMEM63B regulates nucleocytoplasmic transport and placental development.Nature communications · 2026Article
- Schisandrin B Exerts Radiosensitizing Effects on Breast Cancer via Dual Mechanisms of Cell Cycle/DNA Repair and Gut Microbiota-Immune Axis Modulation.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Review
- 4-Hydroxychalcone Exert the Anti-cancer Potential in Colorectal Cancer Through Targeting CDK6.Biological procedures online · 2026Article
- Pseudo-senescence induced by palbociclib does not sensitise pleural mesothelioma cells to combinations with senolytics.Cell death & disease · 2026Article
- Emerging Strategies to Inhibit the G1/S Transition for Cancer Therapy.Cancer research · 2026Review
- Dalpiciclib plus chidamide in HR + /HER2-advanced breast cancer after CDK4/6 inhibitor failure: a phase Ib trial.Nature communications · 2026Article
- Cell size modulates ferroptosis susceptibility.bioRxiv : the preprint server for biology · 2026Article
- Cell enlargement drives aging-associated proteome remodeling and shortens replicative lifespan.bioRxiv : the preprint server for biology · 2026Article
- G1/S arrest: a key mechanism of cellular aging and replicative senescence.Biogerontology · 2026Review
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Authors and funding
21 authors at 5 institutions in 1 country.
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Abstract
Abnormal increases in cell size are associated with senescence and cell cycle exit. The mechanisms by which overgrowth primes cells to withdraw from the cell cycle remain unknown. We address this question using CDK4/6 inhibitors, which arrest cells in G0/G1 and are licensed to treat advanced HR+/HER2- breast cancer. We demonstrate that CDK4/6-inhibited cells overgrow during G0/G1, causing p38/p53/p21-dependent cell cycle withdrawal. Cell cycle withdrawal is triggered by biphasic p21 induction. The first p21 wave is caused by osmotic stress, leading to p38- and size-dependent accumulation of p21. CDK4/6 inhibitor washout results in some cells entering S-phase. Overgrown cells experience replication stress, resulting in a second p21 wave that promotes cell cycle withdrawal from G2 or the subsequent G1. We propose that the levels of p21 integrate signals from overgrowth-triggered stresses to determine cell fate. This model explains how hypertrophy can drive senescence and why CDK4/6 inhibitors have long-lasting effects in patients.
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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.