Pharmacodynamic assessment of AKT and SRC inhibitors in primary human sarcoma xenograft models

The poor outcome of patients with advanced sarcomas underscores the rationale supporting novel therapeutic strategies.  Combination treatment with dasatinib and triciribine effectively blocks growth of sarcoma cell lines through inhibition of SRC and AKT pathways, respectively.  We will determine the activity of these drugs against a set of xenografted tumors obtained from sarcoma patients and analyze pharmacodynamic markers of response using a quantitative multiplex assay platform in vivo.  The studies that would be supported by this application are expected to provide a foundation to support rational clinical trial design for these agents to maximize their therapeutic potential in sarcoma.