Analysis of targeted biological therapies in a genetically engineered mouse model of sarcoma

The development of effective drugs in the treatment of sarcomas is limited by the lack of reliable animal models of sarcomas. This is especially true for drugs that target not only tumor cells but also the interaction between tumor cells and their host microenvironment. Bevacizumab and sunitinib are promising new biological agents that inhibit tumor angiogenesis (or new blood vessel formation) and tumor growth. We recently described an inducible, genetically engineered mouse model of sarcoma where intramuscular delivery of an adenovirus expressing Cre recombinase into mice with conditional mutations in K-ras and p53 results in high-grade sarcomas of the extremity in over 90% of mice. These sarcomas closely resemble human sarcomas based on genetic and histological analysis, and these sarcomas preferentially metastasize to the lung. This study proposes to use this newly developed mouse model of sarcoma (1) to analyze the effects of bevacizumab and sunitinib developed mouse model of sarcoma (2) to analyze the effects of bevacizumab and sunitinib in inhibiting sarcoma growth and metastasis and (3) to identify mechanisms of resistance.