Tumor Angiogenesis in Different Organ Environments: Implications for Anti-VEGF Therapy for Soft Tissue Sarcomas
Anti-angiogenic agents targeting vascular endothelial growth factor (VEGF) and other angiogenic pathways are a major focus of clinical drug development for cancers including soft tissue sarcomas (STS). An underlying premise of these trials is that VEGF inhibition will have equal efficacy in all sites of tumor growth and against all types of endothelial cells. This proposal seeks to develop an angiogenic profile of STS growing in different organs and tissues and to determine if inhibition of VEGF signaling will have varying effects on tumor angiogenesis in different sites. In Specific Aim 1, expression of VEGF and other angiogenesis-related genes in STS will be assessed by ELISA and genechip microarrays. Specific Aim 2 will study the effect of VEGF inhibition using RNA interference (RNAi) and soluble VEGFR-1 (sVEGFR-1) on mouse models of STS growth in different sites. Taken together, the proposed studies should clarify the role that VEGF and other angiogenic factors play in tumor angiogenesis in different environments and provide insight into the future use of antiVEGF therapies in STS.