ArticleOncotarget2016
Pre-clinical efficacy and synergistic potential of the MDM2-p53 antagonists, Nutlin-3 and RG7388, as single agents and in combined treatment with cisplatin in ovarian cancer.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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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
37 citing papers in PubMed, 60 citations in OpenAlex.
- Brigimadlin (BI-907828) and napabucasin (BBI608) cooperatively trigger apoptosis in chronic lymphocytic leukemia cells by simultaneous iİnhibition of MDM2 and STAT3.Molecular biology reports · 2025Article
- Transcription Factors and Methods for the Pharmacological Correction of Their Activity.International journal of molecular sciences · 2025Review
- Targeting MDM2-mediated suppression of p53 with idasanutlin: a promising therapeutic approach for acute lymphoblastic leukemia.Investigational new drugs · 2024Article
- Article
- Splicing Modulation Results in Aberrant Isoforms and Protein Products of p53 Pathway Genes and the Sensitization of B Cells to Non-Genotoxic MDM2 Inhibition.International journal of molecular sciences · 2023Article
- DNA Damage Response Alterations in Ovarian Cancer: From Molecular Mechanisms to Therapeutic Opportunities.Cancers · 2023Review
- miR-16-5p enhances sensitivity to RG7388 through targetingCancer drug resistance (Alhambra, Calif.) · 2023Article
- Simultaneous regression and classification for drug sensitivity prediction using an advanced random forest method.Scientific reports · 2022Article
- Synthesis and Biological Evaluation of Novel Synthetic Indolone Derivatives as Anti-Tumor Agents Targeting p53-MDM2 and p53-MDMX.Molecules (Basel, Switzerland) · 2022Article
- Farnesoid X receptor functions in cervical cancer via the p14Molecular biology reports · 2022Article
- Establishment and characterization of a novel ovarian high-grade serous carcinoma cell line-IPO43.Cancer cell international · 2022Article
- Use of multimodality imaging, histology, and treatment feasibility to characterize a transgenicFrontiers in oncology · 2022Article
- Tipping Growth Inhibition into Apoptosis by Combining Treatment with MDM2 and WIP1 Inhibitors in p53Cancers · 2021Article
- Development of CD133 Targeting Multi-Drug Polymer Micellar Nanoparticles for Glioblastoma - In Vitro Evaluation in Glioblastoma Stem Cells.Pharmaceutical research · 2021Article
- Review
- Ligand-Based and Docking-Based Virtual Screening of MDM2 Inhibitors as Potent Anticancer Agents.Computational and mathematical methods in medicine · 2021Article
- Cellular Mechanism of Gene Mutations and Potential Therapeutic Targets in Ovarian Cancer.Cancer management and research · 2021Review
- The Nuclear Farnesoid X Receptor Reduces p53 Ubiquitination and Inhibits Cervical Cancer Cell Proliferation.Frontiers in cell and developmental biology · 2021Article
- Big data-based identification of methylated genes associated with drug resistance and prognosis in ovarian cancer.Medicine · 2020Article
- MDM2 and MDMX promote ferroptosis by PPARα-mediated lipid remodeling.Genes & development · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ovarian cancer is the fifth leading cause of cancer-related female deaths. Due to serious side effects, relapse and resistance to standard chemotherapy, better and more targeted approaches are required. Mutation of the TP53 gene accounts for 50% of all human cancers. In the remaining malignancies, non-genotoxic activation of wild-type p53 by small molecule inhibition of the MDM2-p53 binding interaction is a promising therapeutic strategy. Proof of concept was established with the cis-imidazoline Nutlin-3, leading to the development of RG7388 and other compounds currently in early phase clinical trials. This preclinical study evaluated the effect of Nutlin-3 and RG7388 as single agents and in combination with cisplatin in a panel of ovarian cancer cell lines. Median-drug-effect analysis showed Nutlin-3 or RG7388 combination with cisplatin was additive to, or synergistic in a p53-dependent manner, resulting in increased p53 activation, cell cycle arrest and apoptosis, associated with increased p21WAF1 protein and/or caspase-3/7 activity compared to cisplatin alone. Although MDM2 inhibition activated the expression of p53-dependent DNA repair genes, the growth inhibitory and pro-apoptotic effects of p53 dominated the response. These data indicate that combination treatment with MDM2 inhibitors and cisplatin has synergistic potential for the treatment of ovarian cancer, dependent on cell genotype.
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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.