ArticlePediatric blood & cancer2015
Inhibition of MDM2 by RG7388 confers hypersensitivity to X-radiation in xenograft models of childhood sarcoma.
Article in Pediatric blood & cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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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.
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Who cites it
19 citing papers in PubMed, 26 citations in OpenAlex.
- Targeting E3 ubiquitin ligases: Mechanistic breakthroughs and novel clinical translation pathways for tumor radioimmunotherapy.Molecular cancer · 2026Review
- Advancements in MDM2 inhibition: Clinical and pre-clinical investigations of combination therapeutic regimens.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2023Review
- Translational Implications for Radiosensitizing Strategies in Rhabdomyosarcoma.International journal of molecular sciences · 2022Review
- Regulation of TORC1 by MAPK Signaling Determines Sensitivity and Acquired Resistance to Trametinib in Pediatric BRAFV600E Brain Tumor Models.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- Phase I study of daily and weekly regimens of the orally administered MDM2 antagonist idasanutlin in patients with advanced tumors.Investigational new drugs · 2021Article
- Clinical and Preclinical Outcomes of Combining Targeted Therapy With Radiotherapy.Frontiers in oncology · 2021Review
- Review
- The role of ubiquitination in tumorigenesis and targeted drug discovery.Signal transduction and targeted therapy · 2020Review
- Molecular characteristics and therapeutic vulnerabilities across paediatric solid tumours.Nature reviews. Cancer · 2019Review
- Evaluation of entinostat alone and in combination with standard-of-care cytotoxic agents against rhabdomyosarcoma xenograft models.Pediatric blood & cancer · 2019Article
- Helping the Released Guardian: Drug Combinations for Supporting the Anticancer Activity of HDM2 (MDM2) Antagonists.Cancers · 2019Review
- Preclinical evaluation of the first intravenous small molecule MDM2 antagonist alone and in combination with temozolomide in neuroblastoma.International journal of cancer · 2019Article
- Prolonged Idasanutlin (RG7388) Treatment Leads to the Generation of p53-Mutated Cells.Cancers · 2018Article
- Radiotherapy increases plasma levels of tumoral cell-free DNA in non-small cell lung cancer patients.Oncotarget · 2018Article
- p53 Nongenotoxic Activation and mTORC1 Inhibition Lead to Effective Combination for Neuroblastoma Therapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Article
- Reviving the guardian of the genome: Small molecule activators of p53.Pharmacology & therapeutics · 2017Review
- Initial Testing (Stage 1) of MK-8242-A Novel MDM2 Inhibitor-by the Pediatric Preclinical Testing Program.Pediatric blood & cancer · 2016Article
- Preclinical Efficacy of the MDM2 Inhibitor RG7112 in MDM2-Amplified and TP53 Wild-type Glioblastomas.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Article
- Reactivation of p53 via MDM2 inhibition.Cell death & disease · 2015Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundCurative therapy for childhood sarcoma presents challenges when complete resection is not possible. Ionizing radiation (XRT) is used as a standard modality at diagnosis or recurrence for childhood sarcoma; however, local recurrence is still problematic. Most childhood sarcomas are TP53 wild type at diagnosis, although approximately 5-10% have MDM2 amplification or overexpression. PROCEDURES: The MDM2 inhibitor, RG7388, was examined alone or in combination with XRT (20Gy given in 2 Gy daily fractions) to immune-deficient mice bearing Rh18 (embryonal) or a total of 30 Gy in 2 Gy fractions to mice bearing Rh30 (alveolar) rhabdomyosarcoma xenografts. RG7388 was administered by oral gavage using two schedules (daily ×5; schedule 1 or once weekly; schedule 2). TP53-responsive gene products (p21, PUMA, DDB2, and MIC1) as well as markers of apoptosis were analyzed.
resultsRG7388 showed no significant single agent antitumor activity. Twenty Grays XRT induced complete regressions (CR) of Rh18 with 100 percent tumor regrowth by week 7, but no tumor regrowth at 20 weeks when combined with RG7388. RG7388 enhanced time to recurrence combined with XRT in Rh30 xenografts compared to 30 Gy XRT alone. RG7388 did not enhance XRT-induced local skin toxicity. Combination treatments induced TP53 responsive genes more rapidly and to a greater magnitude than single agent treatments.
conclusionsRG7388 enhanced the activity of XRT in both rhabdomyosarcoma models without increasing local XRT-induced skin toxicity. Changes in TP53-responsive genes were consistent with the synergistic activity of RG7388 and XRT in the Rh18 model.
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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.