ArticleCell death & disease2018
CDK4 inhibition diminishes p53 activation by MDM2 antagonists.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Clinical Utility of CDK4/6 Inhibitors in Sarcoma: Successes and Future Challenges.JCO precision oncology · 2022Pooled it
- AmpliconSuite: an end-to-end workflow for analyzing focal amplifications in cancer genomes.Nature methods · 2026Article
- 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
- Stratified and Quantified Score Construction of Low-Grade Glioma Samples Based on TP53 Signaling Pathway.BioMed research international · 2026Article
- Prognostic Implications of MDM2 and CDK4 Co-amplification in Liposarcoma: Insights from FISH analysis for Translational Oncology.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
- Article
- Harnessing p53 for targeted cancer therapy: new advances and future directions.Transcription · 2025Review
- Amplification of CDK4 and MDM2: a detailed study of a high-risk neuroblastoma subgroup.Scientific reports · 2022Article
- Real-world use of palbociclib monotherapy in retroperitoneal liposarcomas at a large volume sarcoma center.International journal of cancer · 2022Article
- Targeting the MDM2-p53 pathway in dedifferentiated liposarcoma.Frontiers in oncology · 2022Review
- Resistance mechanisms to inhibitors of p53-MDM2 interactions in cancer therapy: can we overcome them?Cellular & molecular biology letters · 2021Review
- Roles of reactive oxygen species, mitochondrial membrane potential, and p53 in evodiamine-induced apoptosis and G2/M arrest of human anaplastic thyroid carcinoma cells.Chinese medicine · 2021Article
- Long-Term Exposure to Nanosized TiOInternational journal of molecular sciences · 2021Article
- MDM2 as a Rational Target for Intervention in CDK4/6 Inhibitor Resistant, Hormone Receptor Positive Breast Cancer.Frontiers in oncology · 2021Review
- Review
- Rational drug design, synthesis, and biological evaluation of novel chiral tetrahydronaphthalene-fused spirooxindole as MDM2-CDK4 dual inhibitor against glioblastoma.Acta pharmaceutica Sinica. B · 2020Article
- Liposarcoma: Advances in Cellular and Molecular Genetics Alterations and Corresponding Clinical Treatment.Journal of Cancer · 2020Review
- Novel Therapeutic Strategies for CDK4/6 Inhibitors in Metastatic Castrate-Resistant Prostate Cancer.OncoTargets and therapy · 2020Review
- Multiple Chromoanasynthesis in a Rare Case of Sporadic Renal Leiomyosarcoma: A Case Report.Frontiers in oncology · 2020Article
- Regulation of PRMT5-MDM4 axis is critical in the response to CDK4/6 inhibitors in melanoma.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The genes encoding MDM2 and CDK4 are frequently co-amplified in sarcomas, and inhibitors to both targets are approved or clinically tested for therapy. However, we show that inhibitors of MDM2 and CDK4 antagonize each other in their cytotoxicity towards sarcoma cells. CDK4 inhibition attenuates the induction of p53-responsive genes upon MDM2 inhibition. Moreover, the p53 response was also attenuated when co-depleting MDM2 and CDK4 with siRNA, compared to MDM2 single knockdown. The complexes of p53 and MDM2, as well as CDK4 and Cyclin D1, physically associated with each other, suggesting direct regulation of p53 by CDK4. Interestingly, CDK4 inhibition did not reduce p53 binding or histone acetylation at promoters, but rather attenuated the subsequent recruitment of RNA Polymerase II. Taken together, our results suggest that caution must be used when considering combined CDK4 and MDM2 inhibition for patient treatment. Moreover, they uncover a hitherto unknown role for CDK4 and Cyclin D1 in sustaining p53 activity.
Indexed as
Identifiers
What OpenQuestion holds
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.