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.
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.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- Targeting p53 pathways: mechanisms, structures, and advances in therapy.Signal transduction and targeted therapy · 2023Pooled it
- Research Progress on Small Molecule Inhibitors of MDM2-p53 Protein-protein Interaction.Anti-cancer agents in medicinal chemistry · 2026Review
- 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
- Expanding Horizons in Cholangiocarcinoma: Emerging Targets Beyond FGFR2 and IDH1.International journal of molecular sciences · 2025Review
- MDM2 as a therapeutic target in advanced biliary tract cancers.The oncologist · 2025Review
- Review
- Multi-omics analysis revealed potential use of immunotherapy and CDK4/6 inhibitors in intimal sarcoma.Frontiers in immunology · 2025Article
- Oncogenic Functions of Alternatively SplicedInternational journal of molecular sciences · 2024Article
- Discovery and Characterization of Brigimadlin, a Novel and Highly Potent MDM2-p53 Antagonist Suitable for Intermittent Dose Schedules.Molecular cancer therapeutics · 2024Article
- Discovery of MD-265: A Potent MDM2 Degrader That Achieves Complete Tumor Regression and Improves Long-Term Survival of Mice with Leukemia.Journal of medicinal chemistry · 2024Article
- Xenografting Human Musculoskeletal Sarcomas in Mice, Chick Embryo, and Zebrafish: How to Boost Translational Research.Biomedicines · 2024Review
- MDM2 Inhibitors for Cancer Therapy: The Past, Present, and Future.Pharmacological reviews · 2024Review
- Treatment options for biliary tract cancer: unmet needs, new targets and opportunities from both physicians' and patients' perspectives.Future oncology (London, England) · 2024Review
- Neddylation of protein, a new strategy of protein post-translational modification for targeted treatment of central nervous system diseases.Frontiers in neuroscience · 2024Review
- Recent advances in targeting the "undruggable" proteins: from drug discovery to clinical trials.Signal transduction and targeted therapy · 2023Review
- The MDM2-p53 Antagonist Brigimadlin (BI 907828) in Patients with Advanced or Metastatic Solid Tumors: Results of a Phase Ia, First-in-Human, Dose-Escalation Study.Cancer discovery · 2023Article
- MDM2 Inhibition in the Treatment of Glioblastoma: From Concept to Clinical Investigation.Biomedicines · 2023Review
- Ubiquitin-proteasome system as a target for anticancer treatment-an update.Archives of pharmacal research · 2023Review
- Treatment of De-Differentiated Liposarcoma in the Era of Immunotherapy.International journal of molecular sciences · 2023Review
- MDM2 Implications for Potential Molecular Pathogenic Therapies of Soft-Tissue Tumors.Journal of clinical medicine · 2023Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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.
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