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- W2223710040 abstract "The tumor suppressor protein p53 is a transcription factor which plays a crucial role in maintaining genomic stability through the regulation of a vast repertoire of downstream target genes involved in cellular processes, such as cell cycle arrest, apoptosis, senescence, differentiation and DNA repair. Under normal cellular conditions, p53 is tightly regulated by its critical negative regulator MDM2, an E3 ligase which targets p53 for ubiquitin-mediated degradation. p14ARF is a tumor suppressor protein and the negative regulator of MDM2. Together, p53, MDM2 and p14ARF form an autoregulatory loop frequently inactivated in many human cancers. MDM2-p53 antagonists are small-molecule inhibitors designed to disrupt the interaction between p53 and MDM2 thereby nongenotoxically activating p53 in tumors with wild-type p53. Several MDM2-p53 antagonists are undergoing early clinical evaluation in adults and are anticipated to enter pediatric trials in the near future. In contrast to several other cancers, neuroblastoma is a predominantly p53 wild-type tumor; however, p53 pathway inactivation through MDM2 amplification and p14ARF aberrations have been reported. Nongenotoxic activation of wild-type p53 using MDM2-p53 antagonists alone and in combination with other agents offers a novel therapeutic strategy for patients with neuroblastoma to potentially improve survival and/or reduce the toxicity associated with current chemotherapy regimens." @default.
- W2223710040 created "2016-06-24" @default.
- W2223710040 creator A5050562133 @default.
- W2223710040 creator A5053438302 @default.
- W2223710040 date "2015-01-01" @default.
- W2223710040 modified "2023-09-28" @default.
- W2223710040 title "Neuroblastoma and the p53 Pathway" @default.
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- W2223710040 doi "https://doi.org/10.1159/000382087" @default.
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