ArticleOncotarget2017
MDM2 antagonists synergize with PI3K/mTOR inhibition in well-differentiated/dedifferentiated liposarcomas.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 36 citations in OpenAlex.
- Review
- Oncogenic Functions of Alternatively SplicedInternational journal of molecular sciences · 2024Article
- Genetic, Epigenetic and Transcriptome Alterations in Liposarcoma for Target Therapy Selection.Cancers · 2024Review
- MDM2 inhibitor APG-115 synergizes with ABT-199 to induce cell apoptosis in chronic lymphocytic leukemia.Frontiers in pharmacology · 2024Article
- The Molecular Biology of Soft Tissue Sarcomas: Current Knowledge and Future Perspectives.Cancers · 2022Review
- Low-grade osteosarcoma is predominant in gnathic osteosarcomas: A report of seven cases of osteosarcoma of the jaw.Clinical and experimental dental research · 2021Article
- Update on genomic and molecular landscapes of well-differentiated liposarcoma and dedifferentiated liposarcoma.Molecular biology reports · 2021Review
- MDM2/X Inhibitors as Radiosensitizers for Glioblastoma Targeted Therapy.Frontiers in oncology · 2021Review
- Review
- Novel Therapeutic Insights in Dedifferentiated Liposarcoma: A Role for FGFR and MDM2 Dual Targeting.Cancers · 2020Article
- Article
- Triptolide prevents bone loss via suppressing osteoclastogenesis through inhibiting PI3K-AKT-NFATc1 pathway.Journal of cellular and molecular medicine · 2020Article
- Proteomics Analysis for Identification of Potential Cell Signaling Pathways and Protein Targets of Actions of Atractylodin and β-Eudesmol Against Cholangiocarcinoma.Asian Pacific journal of cancer prevention : APJCP · 2020Article
- Helping the Released Guardian: Drug Combinations for Supporting the Anticancer Activity of HDM2 (MDM2) Antagonists.Cancers · 2019Review
- Article
- mTOR Inhibitors in Advanced Biliary Tract Cancers.International journal of molecular sciences · 2019Review
- Animal models of well-differentiated/dedifferentiated liposarcoma: utility and limitations.OncoTargets and therapy · 2019Review
- MDM2-Recruiting PROTAC Offers Superior, Synergistic Antiproliferative Activity via Simultaneous Degradation of BRD4 and Stabilization of p53.Cancer research · 2019Article
- Prolonged Idasanutlin (RG7388) Treatment Leads to the Generation of p53-Mutated Cells.Cancers · 2018Article
- CDK4 inhibition diminishes p53 activation by MDM2 antagonists.Cell death & disease · 2018Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundWell-differentiated/dedifferentiated liposarcoma (WDLPS/DDLPS) are characterized by a consistent amplification of the MDM2 gene. The PI3K/AKT/mTOR pathway has been suggested to play also an important role in their tumorigenesis. Our goal was to determine whether combined MDM2 and PI3K/AKT/mTOR targeting is associated with higher anti-tumor activity than single agent alone in preclinical models of WDLPS/DDLPS.
methodsWDLPS/DDLPS cells were exposed to RG7388 (MDM2 antagonist) and BEZ235 (PI3K/mTOR dual inhibitor) after which apoptosis and signaling/survival pathway perturbations were monitored by flow cytometry and Western blot analysis. Xenograft mouse models were used to assess tumor growth and animal survival. Western blotting, histopathology, and tumor volume evolution were used for the assessment of treatment efficacy.
resultsThe PI3K/AKT/mTOR was upregulated in up to 81% of the human WDLPS/DDLPS samples analysed. Treatment with RG7388 and BEZ235 resulted in a greater tumor activity than either drug alone with a significant difference in terms of cell viability after 72h of treatment with RG-73888 alone, BEZ235 alone and a combination of both agents. Consistent with these observations, we found a significant increase in apoptosis with the combination
conclusionsOur results represent the first in vivo evidence of synergy between MDM2 and PI3K/AKT/mTOR antagonists and represent a strong rationale to evaluate the therapeutic potential of such a combination in WDLPS/DDLPS.
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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.