Partnerships : EWS - FLI 1 Protein Interactions R ate Key Pathways of Ewing ' s Sarcoma

wnloade eted therapy for cancer, which is specifically directed toward the cancer without any potential for outside of controlling the tumor, is a gold standard for treatment. Ewing's sarcoma contains the tial target EWS-FLI1, as a result of a pathognomonic chromosomal translocation. The EWS-FLI1 protein includes the EWS domain, a potent transcriptional activator alongside the highly conserved ts DNA-binding domain. Because of the combination of these domains, the EWS-FLI1 fusion procts as an aberrant transcription factor whose expression results in cellular transformation. EWS-FLI1 ons by binding to normal cellular protein partners in transcription and splicing, similar to how a would corrupt normal cellular machinery for virion production. Therefore, understanding the n-protein interactions of EWS-FLI1 and the pathways that are regulated by these partnerships will both oncogenesis and therapeutics. This review describes the known protein partners and inform transcriptional targets of EWS-FLI1, while proposing strategies for exploiting these partnerships with targeted therapy. Clin Cancer Res; 16(16); 4077–83. ©2010 AACR.