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Sarcoma
Volume 2011, Article ID 746939, 17 pages
http://dx.doi.org/10.1155/2011/746939
Review Article

Targeting the p53 Pathway in Ewing Sarcoma

1Sarcoma Research Group, Discipline of Medicine, University of Adelaide and Hanson Institute, Frome Road, Adelaide, SA 5000, Australia
2Ian Potter Foundation Centre for Cancer Genomics and Predictive Medicine, Peter MacCallum Cancer Centre, East Melbourne, VIC 3002, Australia

Received 4 July 2010; Accepted 28 October 2010

Academic Editor: Alessandro Gronchi

Copyright © 2011 Paul M. Neilsen et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.