Micro-environmental Regulators of Ewing sarcoma Metastasis
This project focuses on Ewing’s Sarcoma, a cancer of the bone or soft tissue that predominately affects adolescents. Although patients with localized disease are often cured, the prognosis for patients with metastatic disease is dismal, with survival estimates as low as 10%. We do not yet understand why some Ewing’s Sarcoma cells metastasize, and patient outcomes will not improve until we fill this critical knowledge gap.
As tumors grow, they are deprived of oxygen and nutrients. We have found that Ewing’s cells are more aggressive in this deprived state. We will investigate how these changes in Ewing’s cells occur. In addition, we will test how traditional chemotherapy invokes changes in cell behavior that could encourage metastatic spread. Finally, we will investigate how the Wnt pathway (a cell signaling pathway active in normal bone development) may change the ability of Ewing’s cells to metastasize. We propose that both stress responses and the Wnt pathway are key factors that lead to Ewing’s Sarcoma metastasis. The long-term goal of this project is to unveil novel mechanisms to prevent and treat metastatic Ewing’s Sarcoma.