Potentials for RNAi in sarcoma research and therapy: Ewing's sarcoma as a model.
Existing data identify EWS-FLI1 as indispensable for sustained Ewing's sarcoma growth and as the ideal therapeutic target in this disease. The siRNA may hold great promises as a fusion gene specific agent. RNAi mediated suppression of EWS-FLI1 is likely to result in an altered tumor cell phenotype including changes in chemosensitivity, and a restored differentiation potential. Thus, RNAi may serve as an adjuvant to chemotherapy. As a therapeutic means however, RNAi is hampered by limitations in the delivery of the agent and emergence of resistant clones. In vitro suppression of EWS-FLI1 expression will allow to define the phenotypic characteristics of dormant tumor cells that may give rise to late relapses, enabling improved diagnosis and treatment even of minimal residual disease.
Kovar
Heinrich
H
Children's Cancer Research Institute, St. Anna Kinderspital, Kinderspitalgasse 6, A-1090 Vienna, Austria. heinrich.kovar@ccri.univie.ac.at
Ban
Josef
J
Pospisilova
Sarka
S
D000818:Animals; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008954:Models, Biological; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D051789:Proto-Oncogene Protein c-fli-1; D034622:RNA Interference; D034802:RNA-Binding Protein EWS; D012512:Sarcoma, Ewing / Q000235:genetics / Q000628:therapy*; D014157:Transcription Factors / Q000235:genetics*
C106031:EWS-FLI fusion protein; D015514:Oncogene Proteins, Fusion; D051789:Proto-Oncogene Protein c-fli-1; D034802:RNA-Binding Protein EWS; D014157:Transcription Factors