Targeting the p53 Pathway in Ewing Sarcoma. (9th December 2010)

• Record Type: Journal Article
• Authors: Neilsen, Paul M.; Pishas, Kathleen I.; Callen, David F.; Thomas, David M.
• Other Names: Gronchi Alessandro Academic Editor.
• Is Part Of: Sarcoma. Volume 2011(2011)
• Publication Date: 2010-12-09
• Subjects: Sarcoma -- Periodicals; 616.994
• DOI: 10.1155/2011/746939
• Languages: English
• ISSNs: 1357-714X

Abstract

Abstract : The p53 tumour suppressor plays a pivotal role in the prevention of oncogenic transformation. Cancers frequently evade the potent antitumour surveillance mechanisms of p53 through mutation of the TP53 gene, with approximately 50% of all human malignancies expressing dysfunctional, mutated p53 proteins. Interestingly, genetic lesions in the TP53 gene are only observed in 10% of Ewing Sarcomas, with the majority of these sarcomas expressing a functional wild-type p53. In addition, the p53 downstream signaling pathways and DNA-damage cell cycle checkpoints remain functionally intact in these sarcomas. This paper summarizes recent insights into the functional capabilities and regulation of p53 in Ewing Sarcoma, with a particular focus on the cross-talk between p53 and the EWS-FLI1 gene rearrangement frequently associated with this disease. The development of several activators of p53 is discussed, with recent evidence demonstrating the potential of small molecule p53 activators as a promising systemic therapeutic approach for the treatment of Ewing Sarcomas with wild-type p53.