ArticleOncotarget2015
MDM2 turnover and expression of ATRX determine the choice between quiescence and senescence in response to CDK4 inhibition.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 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
83 citing papers in PubMed, 142 citations in OpenAlex.
- Overall survival from the open-label phase II trial of palbociclib in patients with advanced well-differentiated/dedifferentiated liposarcoma.ESMO open · 2026Trial
- Trial
- Tumor and Immune Dynamics Following Sequential CDK4/6 and PD-1 Inhibition: Results from a Phase 2 Study in Dedifferentiated Liposarcoma.Cancer research communications · 2026Trial
- Modulation of the Estrogen/erbB2 Receptors Cross-talk by CDK4/6 Inhibition Triggers Sustained Senescence in Estrogen Receptor- and ErbB2-positive Breast Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Trial
- Progression-Free Survival Among Patients With Well-Differentiated or Dedifferentiated Liposarcoma Treated With CDK4 Inhibitor Palbociclib: A Phase 2 Clinical Trial.JAMA oncology · 2016Trial
- CDK4/6 inhibition induces a senescence-associated secretory phenotype via delayed NF-κB activation.Life science alliance · 2026Article
- Advances in Cutaneous Melanoma Therapy: The Emerging Role of CDK4/6 Inhibitors.Pharmacological research · 2025Review
- Deep Introspection Regarding Cumulative Prognostic Factors in Liposarcoma and Atypical Lipomatous Tumor.Medicina (Kaunas, Lithuania) · 2025Article
- Targeting CDKs in cancer therapy: advances in PROTACs and molecular glues.NPJ precision oncology · 2025Review
- Review
- Article
- HRK downregulation and augmented BCL-xL binding to BAK confer apoptotic protection to therapy-induced senescent melanoma cells.Cell death and differentiation · 2025Article
- Senolytics: charting a new course or enhancing existing anti-tumor therapies?Cellular oncology (Dordrecht, Netherlands) · 2025Review
- Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i): Mechanisms of resistance and where to find them.Breast (Edinburgh, Scotland) · 2025Review
- Adjuvant endocrine therapy with cyclin-dependent kinase 4/6 inhibitor, ribociclib, for localized hormone receptor-positive/HER2- breast cancer (LEADER).NPJ breast cancer · 2025Article
- "Enhancing Liposarcoma Prognosis - A New Predictive Scoring System Integrating Histopathological Insights".Cancer management and research · 2025Article
- Long-term breast cancer response to CDK4/6 inhibition defined by TP53-mediated geroconversion.Cancer cell · 2024Article
- HER4 Affects Sensitivity to Tamoxifen and Abemaciclib in Luminal Breast Cancer Cells and Restricts Tumor Growth in MCF-7-Based Humanized Tumor Mice.International journal of molecular sciences · 2024Article
- Article
- Adjuvant CDK4/6 Inhibitors for Early Breast Cancer: How to Choose Wisely?Oncology and therapy · 2024Article
23 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
CDK4 inhibitors (CDK4i) earned Breakthrough Therapy Designation from the FDA last year and are entering phase III clinical trials in several cancers. However, not all tumors respond favorably to these drugs. CDK4 activity is critical for progression through G1 phase and into the mitotic cell cycle. Inhibiting this kinase induces Rb-positive cells to exit the cell cycle into either a quiescent or senescent state. In this report, using well-differentiated and dedifferentiated liposarcoma (WD/DDLS) cell lines, we show that the proteolytic turnover of MDM2 is required for CDK4i-induced senescence. Failure to reduce MDM2 does not prevent CDK4i-induced withdrawal from the cell cycle but the cells remain in a reversible quiescent state. Reducing MDM2 in these cells drives them into the more stable senescent state. CDK4i-induced senescence associated with loss of MDM2 is also observed in some breast cancer, lung cancer and glioma cell lines indicating that this is not limited to WD/DDLS cells in which MDM2 is overexpressed or in cells that contain wild type p53. MDM2 turnover depends on its E3 ligase activity and expression of ATRX. Interestingly, in seven patients the changes in MDM2 expression were correlated with outcome. These insights identify MDM2 and ATRX as new regulators controlling geroconversion, the process by which quiescent cells become senescent, and this insight may be exploited to improve the activity of CDK4i in cancer therapy.
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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.