976: Investigating the Role of STAT3 Activation in Canine Osteosarcoma
Grant Status: Closed
The purpose of this research was to characterize the role of STAT3 in canine osteosarcoma to assess whether this protein represents a novel target for future therapeutic intervention. Dr. London's research team has made significant progress over the 2 year project, defining STAT3 as important for the growth and survival of osteosarcoma cells and identifying small molecule inhibitors capable of blocking STAT3 function. More recently they have been investigating the potential utility of a derivative of the spice curcumin that blocks STAT3. This derivative, FLLL32, was engineered from curcumin by the Medicinal Chemistry group at OSU to be more potent and more specific for targeting of STAT3 than curcumin. Work with this exciting new product is ongoing. Lastly, they have begun to identify factors that may be responsible for the observed activation of STAT3 in osteosarcoma and this will likely provide a broader range of future targets for therapeutic intervention. The overriding goal of this work was to eventually bring STAT3 inhibitors into clinical trials of dogs with osteosarcoma.
Fossey, S. L., Bear, M. D., Kisseberth, W. C., Pennell, M., & London, C. A. (2011). Oncostatin M promotes STAT3 activation, VEGF production, and invasion in osteosarcoma cell lines. BMC Cancer, 11(1). https://doi.org/10.1186/1471-2407-11-125
Fossey, S. L., Bear, M. D., Lin, J., Li, C., Schwartz, E. B., Li, P.-K., … London, C. A. (2011). The novel curcumin analog FLLL32 decreases STAT3 DNA binding activity and expression, and induces apoptosis in osteosarcoma cell lines. BMC Cancer, 11(1). https://doi.org/10.1186/1471-2407-11-112
Fossey, S. L., Liao, A. T., McCleese, J. K., Bear, M. D., Lin, J., Li, P.-K., … London, C. A. (2009). Characterization of STAT3 activation and expression in canine and human osteosarcoma. BMC Cancer, 9(1). https://doi.org/10.1186/1471-2407-9-81
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