ArticleJournal of hematology & oncology2017
Combined targeting of MDM2 and CDK4 is synergistic in dedifferentiated liposarcomas.
Article in Journal of hematology & oncology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 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
68 citing papers in PubMed, 1 synthesis or guideline pooled it, 115 citations in OpenAlex.
- Clinical Utility of CDK4/6 Inhibitors in Sarcoma: Successes and Future Challenges.JCO precision oncology · 2022Pooled it
- Review
- 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
- Immunocompetent Murine Models Recapitulate the Heterogeneous Tumor-Immune Microenvironment of Human Liposarcoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Targeting tGLI1, a novel mediator of tumor therapeutic resistance, using Ketoconazole sensitizes glioblastoma to CDK4/6 therapy and chemoradiation.bioRxiv : the preprint server for biology · 2025Article
- Primary giant liposarcoma of the gallbladder: a case report and literature review.World journal of surgical oncology · 2025Review
- Bibliometric analysis of liposarcomas treatment from 2004 to 2023.Journal of cancer research and clinical oncology · 2025Article
- CDK4/6 inhibitors in breast cancer therapy: mechanisms of drug resistance and strategies for treatment.Frontiers in pharmacology · 2025Review
- Three-dimensional models: from cell culture to Patient-Derived Organoid and its application to future liposarcoma research.Oncology research · 2025Review
- Ursodeoxycholic acid inhibits the uptake of cystine through SLC7A11 and impairsJournal of pharmaceutical analysis · 2025Article
- Genetic, Epigenetic and Transcriptome Alterations in Liposarcoma for Target Therapy Selection.Cancers · 2024Review
- Advancements in MDM2 inhibition: Clinical and pre-clinical investigations of combination therapeutic regimens.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2023Review
- Review
- Clinical and Genomic Characteristics of Patients with Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer Following Progression on Cyclin-Dependent Kinase 4 and 6 Inhibitors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- A narrative review about CDK4/6 inhibitors in the setting of drug resistance: updates on biomarkers and therapeutic strategies in breast cancer.Translational cancer research · 2023Review
- MicroRNA-215-5p promotes proliferation, invasion, and inhibits apoptosis in liposarcoma cells by targeting MDM2.Cancer medicine · 2023Article
- [A case report of adult primary soft tissue sarcoma of the head and neck].Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology head and neck surgery · 2023Article
- Targeting cyclin-dependent kinases in sarcoma treatment: Current perspectives and future directions.Frontiers in oncology · 2023Review
- Applications and mechanisms of the cyclin-dependent kinase 4/6 inhibitor, PD-0332991, in solid tumors.Cellular oncology (Dordrecht, Netherlands) · 2022Review
- CDK4/6 inhibitor resistance mechanisms and treatment strategies (Review).International journal of molecular medicine · 2022Review
8 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
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeMDM2 and CDK4 are frequently co-amplified in well-differentiated/dedifferentiated liposarcoma (WDLPS/DDLPS). We aimed to determine whether combined MDM2/CDK4 targeting is associated with higher antitumour activity than a single agent in preclinical models of DDLPS. EXPERIMENTAL
designDDLPS cells were exposed to RG7388 (MDM2 antagonist) and palbociclib (CDK4 inhibitor), and apoptosis and signalling/survival pathway perturbations were monitored by flow cytometry and Western blotting. Xenograft mouse models were used to assess tumour growth and survival. Treatment efficacy was assessed by Western blotting, histopathology and tumour volume.
resultsRG7388 and palbociclib together exerted a greater antitumour effect than either drug alone, with significant differences in cell viability after a 72-h treatment with RG7388 and/or palbociclib. The combination treatment significantly increased apoptosis compared to the single agents. We then analysed the in vivo antitumour activity of RG7388 and palbociclib in a xenograft model of DDLPS. The combination regimen reduced the tumour growth rate compared with a single agent alone and significantly increased the median progression-free survival.
conclusionsOur results provide a strong rationale for evaluating the therapeutic potential of CDK4 inhibitors as potentiators of MDM2 antagonists in DDLPS and justify clinical trials in this setting.
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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.