13080 Background: Soft tissue sarcomas are malignant tumors that can develop from a variety of tissues. There is a lack of targeted therapies directed specifically against sarcomas with surgery, radiation, and chemotherapy being the standard of care. By employing multiple strategies, new targets that may advance sarcoma therapy can be identified. Methods: Profiling of secreted cytokines that may drive tumor growth was performed on cell lines representing osteosarcomas, liposarcomas, fibrosarcomas, and rhabdomysarcomas. Of 27 cytokines analyzed from cultured media, the following were most highly expressed: IL-6, IL-8, IL-12p40, SDF-1, and MCP-1. Results: Results were compared against gene expression data from publicly available oligonucleotide microarrays derived from human tumors. Ewing’s sarcoma and rhabdomysarcoma samples confirmed higher expression levels of VEGF. Further analysis of array data from 16 classes of sarcomas and 181 tumors indicated that IL-7 was more predominantly expressed than IL-6 and IL-8. To evaluate efficacy of novel agents, xenograft models were established using human cell lines A673 rhabdomyosarcoma and SW872 liposarcoma. Tumor growth and response to therapy was characterized. Paclitaxel (75 mg/kg, days 7, 9, 11) delayed tumor growth for about one week following treatment in both models, however only SW872 liposarcoma tumors responded after dosing with anti-angiogenic agent, Avastin (5 mg/kg, days 4, 7, 11, 14, 17, and 21). Conclusions: In addition to killing cancer cells, destabilization of the vasculature/stroma may be beneficial. Immunohistochemical (IHC) analysis was performed on sarcoma tumors from the clinic. CD31 and SMA staining identified vasculature and stromal regions. Subsequent to identification of novel targets specific to sarcomas, IHC methods can further define localization of antigens between various tumor components. A variety of techniques are being utilized in order to recognize new targets in sarcomas. Cell-based assays and preclinical models are incorporated into the drug development pathway to evaluate novel drugs. Analysis of differential gene expression between tumor types and amongst sarcoma subtypes will be essential in identifying which patient population will gain the greatest benefits from targeted therapies. [Table: see text]