Trial reportNature communications2016
TP53 mutations emerge with HDM2 inhibitor SAR405838 treatment in de-differentiated liposarcoma.
Trial report in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 2 of them syntheses 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
61 citing papers in PubMed, 2 syntheses or guidelines pooled it, 92 citations in OpenAlex.
- Precision medicine in diagnosis, prognosis, and disease monitoring of bone and soft tissue sarcomas using liquid biopsy: a systematic review.Archives of orthopaedic and trauma surgery · 2025Pooled it
- Targeting p53 pathways: mechanisms, structures, and advances in therapy.Signal transduction and targeted therapy · 2023Pooled it
- Milademetan in Advanced Solid Tumors with MDM2 Amplification and Wild-type TP53: Preclinical and Phase II Clinical Trial Results.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- p53-R280S mutation confers lenvatinib resistance in hepatocellular carcinoma via Bcl-2-mediated anti-apoptotic signaling.Molecular and cellular biochemistry · 2026Article
- Revisiting tumor immunogenicity through the lens of mutant p53: Implications for cancer immunotherapy.Apoptosis : an international journal on programmed cell death · 2026Review
- The Enigmatic Tumor Suppressor p53 Biomolecule: Its Role and Prognostic and Predictive Values in Cancer Therapy and Precision Medicine.Biomolecules · 2026Review
- Population PK/PD Modeling for Evaluation of Intertwining Effects of Drug and Disease on Thrombocytopenia in Acute Leukemias.CPT: pharmacometrics & systems pharmacology · 2026Article
- The TP53 tumor suppressor gene: From molecular biology to clinical investigations.Journal of internal medicine · 2025Review
- MD-4251: A First-in-Class Oral MDM2 Degrader Inducing Complete Tumor Regression with Single-Dose Administration.Journal of medicinal chemistry · 2025Article
- Anticancer Quinolinol Small Molecules Target Multiple Pathways to Promote Cell Death and Eliminate Melanoma Cells Resistant to BRAF Inhibitors.Molecules (Basel, Switzerland) · 2025Article
- MDM2 inhibition is associated with the emergence of TP53-altered clonal hematopoiesis.NPJ precision oncology · 2025Article
- Novel Inhibitors for MDM2-MDM4 E3 Ligase Potently Induce p53-Indepedent Apoptosis in Drug-Resistant Leukemic Cells.Molecules (Basel, Switzerland) · 2025Article
- 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
- Combination of MDM2 and Targeted Kinase Inhibitors Results in Prolonged Tumor Control in Lung Adenocarcinomas With Oncogenic Tyrosine Kinase Drivers andJCO precision oncology · 2024Article
- Understanding the complexity of p53 in a new era of tumor suppression.Cancer cell · 2024Review
- Pleomorphic Liposarcoma Unraveled: Investigating Histopathological and Immunohistochemical Markers for Tailored Diagnosis and Therapeutic Innovations.Medicina (Kaunas, Lithuania) · 2024Review
- Anticancer therapeutic strategies for targeting mutant p53-Y220C.Journal of biomedical research · 2024Article
- Translating p53-based therapies for cancer into the clinic.Nature reviews. Cancer · 2024Review
- Small-molecule MMRi36 induces apoptosis in p53-mutant lymphomas by targeting MDM2/MDM4/XIAP for degradation.Frontiers in oncology · 2024Article
- Primary dedifferentiated liposarcoma of the gallbladder: a case report and literature review.Frontiers in surgery · 2024Article
1 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
14 authors at 9 institutions in 3 countries.
Funding
Abstract
In tumours that harbour wild-type p53, p53 protein function is frequently disabled by the mouse double minute 2 protein (MDM2, or HDM2 in humans). Multiple HDM2 antagonists are currently in clinical development. Preclinical data indicate that TP53 mutations are a possible mechanism of acquired resistance to HDM2 inhibition; however, this resistance mechanism has not been reported in patients. Utilizing liquid biopsies, here we demonstrate that TP53 mutations appear in circulating cell-free DNA obtained from patients with de-differentiated liposarcoma being treated with an inhibitor of the HDM2-p53 interaction (SAR405838). TP53 mutation burden increases over time and correlates with change in tumour size, likely representing selection of TP53 mutant clones resistant to HDM2 inhibition. These results provide the first clinical demonstration of the emergence of TP53 mutations in response to an HDM2 antagonist and have significant implications for the clinical development of this class of molecules.
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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.