期刊
CLINICAL CANCER RESEARCH
卷 16, 期 16, 页码 4077-4083出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-09-2261
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资金
- Children's Cancer Foundation of Baltimore, Maryland
- Go4theGoal
- Dani's Foundation
- Alex's Lemonade Stand Foundation
- Liddy Shriver Sarcoma Initiative
- Amschwand Sarcoma Foundation
- AFLAC Foundation
- Burroughs Wellcome Clinical Scientist Award in Translational Research
- NIH National Cancer Institute
- Emerging Frontiers
- Direct For Biological Sciences [0849803] Funding Source: National Science Foundation
Targeted therapy for cancer, which is specifically directed toward the cancer without any potential for effects outside of controlling the tumor, is a gold standard for treatment. Ewing's sarcoma contains the potential target EWS-FLI1, as a result of a pathognomonic chromosomal translocation. The EWS-FLI1 fusion protein includes the EWS domain, a potent transcriptional activator alongside the highly conserved FLI1 ets DNA-binding domain. Because of the combination of these domains, the EWS-FLI1 fusion protein acts as an aberrant transcription factor whose expression results in cellular transformation. EWS-FLI1 functions by binding to normal cellular protein partners in transcription and splicing, similar to how a virus would corrupt normal cellular machinery for virion production. Therefore, understanding the protein-protein interactions of EWS-FLI1 and the pathways that are regulated by these partnerships will inform both oncogenesis and therapeutics. This review describes the known protein partners and transcriptional targets of EWS-FLI1, while proposing strategies for exploiting these partnerships with targeted therapy. Clin Cancer Res; 16(16); 4077-83. (C) 2010 AACR.
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