Evidence mapPaperPMID 31201607Full record

ArticleClinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico2020

Anti-tumor activity of the MDM2-TP53 inhibitor BI-907828 in dedifferentiated liposarcoma patient-derived xenograft models harboring MDM2 amplification.

J Cornillie, A Wozniak, H Li, Y K Gebreyohannes, J Wellens, D Hompes, M Debiec-Rychter, R Sciot, P Schöffski

Abstract read
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In one paragraph

Article in Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed, 1 pooled it
2.6field-weighted citation impact, top 10% of its field
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

36 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.

  1. Targeting p53 pathways: mechanisms, structures, and advances in therapy.Signal transduction and targeted therapy · 2023
    Pooled it
  2. Review
  3. 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 · 2025
    Article
  4. Review
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  8. Oncogenic Functions of Alternatively SplicedInternational journal of molecular sciences · 2024
    Article
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  19. Treatment of De-Differentiated Liposarcoma in the Era of Immunotherapy.International journal of molecular sciences · 2023
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 1 institution in 1 country.

J CornillieLaboratory of Experimental Oncology, Department of Oncology and Department of General Medical Oncology, Leuven Cancer Institute, KU Leuven and University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium. jasmien.cornillie@uzleuven.be.ORCID http://orcid.org/0000-0001-9793-7163
A WozniakLaboratory of Experimental Oncology, Department of Oncology and Department of General Medical Oncology, Leuven Cancer Institute, KU Leuven and University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium.
H LiLaboratory of Experimental Oncology, Department of Oncology and Department of General Medical Oncology, Leuven Cancer Institute, KU Leuven and University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium.
Y K GebreyohannesLaboratory of Experimental Oncology, Department of Oncology and Department of General Medical Oncology, Leuven Cancer Institute, KU Leuven and University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium.
J WellensLaboratory of Experimental Oncology, Department of Oncology and Department of General Medical Oncology, Leuven Cancer Institute, KU Leuven and University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium.
D HompesDepartment of Surgical Oncology, KU Leuven and University Hospitals Leuven, Leuven, Belgium.
M Debiec-RychterDepartment of Human Genetics, KU Leuven and University Hospitals Leuven, Leuven, Belgium.
R SciotDepartment of Pathology, KU Leuven and University Hospitals Leuven, Leuven, Belgium.
P SchöffskiLaboratory of Experimental Oncology, Department of Oncology and Department of General Medical Oncology, Leuven Cancer Institute, KU Leuven and University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium.
KU Leuven · BE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeDedifferentiated liposarcoma (DDLPS) is a soft tissue malignancy characterized by amplification of the mouse double minute 2 homolog (MDM2) gene. MDM2 is a negative regulator of tumor protein 53 (TP53). We tested the in vivo efficacy of BI-907828, a small molecule inhibitor of the MDM2-TP53 interaction, in two DDLPS patient-derived xenografts (PDX).

methodsPartially immunodeficient mice were bilaterally engrafted with UZLX-STS3 (n = 24) and UZLX-STS5 (n = 24) human DDLPS tissue harboring MDM2 amplifications. Mice were grouped as follows: (a) vehicle (0.5% hydroxyethylcellullose) 10 ml/kg daily per os (p.o.); (b) doxorubicin 5 mg/kg weekly intraperitoneally (i.p.); (c) BI-907828 2.5 mg/kg daily p.o. and (d) BI-907828 10 mg/kg daily p.o. The treatment lasted for 15 days, all mice treated with BI-907828 were followed for 37 days post-treatment. Efficacy was assessed by tumor volume and histopathological evaluation.

resultsThe 15-day treatment with 2.5 mg/kg and 10 mg/kg BI-907828 significantly inhibited tumor growth in UZLX-STS5 and -STS3 (p < 0.0001 compared to control for both models). All UZLX-STS5 and -STS3 tumors treated with BI-907828 decreased in size during treatment, and BI-907828-treated UZLX-STS5 tumors even disappeared completely. During the follow-up period, no tumor regrowth was observed in the UZLX-STS5 model and both doses of BI-907828 led to a pathological complete response, whereas a dose-dependent regrowth was seen in the UZLX-STS3 model.

conclusionBI-907828 showed significant anti-tumor activity in DDLPS PDX harboring MDM2 amplifications, providing a strong rationale for early clinical testing of BI-907828 in a DDLPS patient population.

Indexed as

Gene AmplificationAnimalsAntineoplastic AgentsDoxorubicinGene DosageHeterocyclic Compounds, 4 or More RingsHumansLiposarcomaMiceOrganic ChemicalsProto-Oncogene Proteins c-mdm2Spiro CompoundsTumor Suppressor Protein p53Xenograft Model Antitumor AssaysAntineoplastic AgentsbrigimadlinDoxorubicinHeterocyclic Compounds, 4 or More RingsOrganic ChemicalsProto-Oncogene Proteins c-mdm2Spiro CompoundsTumor Suppressor Protein p53Dedifferentiated liposarcomaMDM2-TP53 inhibitorMouse double minute 2 homolog (MDM2) amplificationPatient-derived xenograftsTumor protein 53 (TP53)

Identifiers

PMID31201607
OpenAlexW2951587879

What Socratic holds

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Registered trials

None linked

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 Socratic graph.