ArticleOncotarget2016
Cooperation of Nutlin-3a and a Wip1 inhibitor to induce p53 activity.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 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
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- The role of PPM1D in cancer and advances in studies of its inhibitors.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2020Pooled it
- ITGB4 up-regulated by STAT3 reduces the sensitivity of bladder cancer to cisplatin by suppressing p53.British journal of cancer · 2026Article
- Research Progress on Small Molecule Inhibitors of MDM2-p53 Protein-protein Interaction.Anti-cancer agents in medicinal chemistry · 2026Review
- Harnessing p53 for targeted cancer therapy: new advances and future directions.Transcription · 2025Review
- PP2C phosphatases-terminators of suicidal thoughts.Cell death & disease · 2024Review
- Rescue of p53 functions by in vitro-transcribed mRNA impedes the growth of high-grade serous ovarian cancer.Cancer communications (London, England) · 2024Article
- miR-16-5p enhances sensitivity to RG7388 through targetingCancer drug resistance (Alhambra, Calif.) · 2023Article
- PPM1D suppresses p53-dependent transactivation and cell death by inhibiting the Integrated Stress Response.Nature communications · 2022Article
- Article
- Tipping Growth Inhibition into Apoptosis by Combining Treatment with MDM2 and WIP1 Inhibitors in p53Cancers · 2021Article
- Resistance mechanisms to inhibitors of p53-MDM2 interactions in cancer therapy: can we overcome them?Cellular & molecular biology letters · 2021Review
- Article
- Analysis framework and experimental design for evaluating synergy-driving gene expression.Nature protocols · 2021Article
- Tumor-Associated Antigen xCT and Mutant-p53 as Molecular Targets for New Combinatorial Antitumor Strategies.Cells · 2021Review
- Therapeutic opportunities in cancer therapy: targeting the p53-MDM2/MDMX interactions.American journal of cancer research · 2021Review
- Design, Synthesis, and Biological Evaluation of Aromatic Amide-Substituted Benzimidazole-Derived Chalcones. The Effect of UpregulatingMolecules (Basel, Switzerland) · 2020Article
- Article
- Helping the Released Guardian: Drug Combinations for Supporting the Anticancer Activity of HDM2 (MDM2) Antagonists.Cancers · 2019Review
- Inhibition of invasive pancreatic cancer: restoring cell apoptosis by activating mitochondrial p53.American journal of cancer research · 2019Article
- Etoposide-resistance in a neuroblastoma model cell line is associated with 13q14.3 mono-allelic deletion and miRNA-15a/16-1 down-regulation.Scientific reports · 2018Article
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 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Targeting the Mdm2 oncoprotein by drugs has the potential of re-establishing p53 function and tumor suppression. However, Mdm2-antagonizing drug candidates, e. g. Nutlin-3a, often fail to abolish cancer cell growth sustainably. To overcome these limitations, we inhibited Mdm2 and simultaneously a second negative regulator of p53, the phosphatase Wip1/PPM1D. When combining Nutlin-3a with the Wip1 inhibitor GSK2830371 in the treatment of p53-proficient but not p53-deficient cells, we observed enhanced phosphorylation (Ser 15) and acetylation (Lys 382) of p53, increased expression of p53 target gene products, and synergistic inhibition of cell proliferation. Surprisingly, when testing the two compounds individually, largely distinct sets of genes were induced, as revealed by deep sequencing analysis of RNA. In contrast, the combination of both drugs led to an expression signature that largely comprised that of Nutlin-3a alone. Moreover, the combination of drugs, or the combination of Nutlin-3a with Wip1-depletion by siRNA, activated p53-responsive genes to a greater extent than either of the compounds alone. Simultaneous inhibition of Mdm2 and Wip1 enhanced cell senescence and G2/M accumulation. Taken together, the inhibition of Wip1 might fortify p53-mediated tumor suppression by Mdm2 antagonists.
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.