Table of Contents
ISRN Oncology
Volume 2012, Article ID 247657, 13 pages
http://dx.doi.org/10.5402/2012/247657
Review Article

Ewing's Sarcoma: Development of RNA Interference-Based Therapy for Advanced Disease

1Gradalis, Inc., Dallas, TX 75201, USA
2Mary Crowley Cancer Research Centers, Dallas, TX 75201, USA
3Texas Oncology, PA, Dallas, TX 75251, USA
4Medical City Dallas Hospital, Dallas, TX 75230, USA

Received 27 October 2011; Accepted 4 December 2011

Academic Editors: B. Fang, F. Kuhnel, and M. Stracke

Copyright © 2012 Olivia Simmons 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

Ewing's sarcoma tumors are associated with chromosomal translocation between the EWS gene and the ETS transcription factor gene. These unique target sequences provide opportunity for RNA interference(i)-based therapy. A summary of RNAi mechanism and therapeutically designed products including siRNA, shRNA and bi-shRNA are described. Comparison is made between each of these approaches. Systemic RNAi-based therapy, however, requires protected delivery to the Ewing's sarcoma tumor site for activity. Delivery systems which have been most effective in preclinical and clinical testing are reviewed, followed by preclinical assessment of various silencing strategies with demonstration of effectiveness to EWS/FLI-1 target sequences. It is concluded that RNAi-based therapeutics may have testable and achievable activity in management of Ewing's sarcoma.