Developing Tumor Specific Therapy

The therapeutic implications of sarcoma-specific gene fusion events are tremendous, since each fusion is a potential target for tumor-specific therapies. A tumor-specific cytotoxic T-cell response can be induced by peptides derived from the fusion point of the SYT-SSX chimeric protein in synovial sarcoma that may function in vitro as a neoantigen.40 Other forms of tumor-specific immunotherapies are under development. STI571 (Gleevec) is a potent, relatively selective inhibitor for the BCR-ABL tyrosine kinase of chronic myelogenous leukemia. STI571 is being successfully used to treat gastrointestinal stromal tumors with KIT mutational activation,41 and it has been shown to reduce the growth of COL1A1-PDGFB-transformed animal cells as well as primary cultures of DFSP tumor cells in vitro and in vivo.6,42 These successes have opened the door to the design of tumor-specific drugs targeting the fusion proteins present in soft tissue sarcomas. Furthermore, specific fusion transcripts also may be targeted through the RNA interference mechanism43 or by other gene therapy approaches.44,45

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