Can active beta-catenin (ABC) be used as a marker to predict osteosarcoma progression to aggressive/metastatic disease?
Impact and Significance: Osteosarcoma (OS), a type of primary bone cancer, has a high incidence rate in children and adolescents. Spreading (Metastasis) of tumor cells to distant sites (mostly lungs) and poor response to current treatments are major causes for poor survival in patients. There is a real need to develop new strategies for early detection and effective treatment to improve survival. Currently, there are no reliable prognostic marker to determine aggressive disease/likelihood of tumor metastasis. Identifying markers for aggressive disease would facilitate risk stratification. We are studying the role of a protein called β-catenin, specifically its active form, Active Beta-Catenin (ABC) in OS progression. β-catenin is known to be important in bone development. Previous Research: Results from our lab show that ABC levels increases as OS progresses to a more aggressive/ metastatic disease. Objective: Investigate whether ABC plays a role in OS progression and can be used as a prognostic marker for aggressive disease. Aim 1: Does ABC play a role in promoting aggressive/metastatic OS? This aim will inform whether ABC is functionally involved in regulating OS progression. Aim 2: Can ABC be used as a prognostic marker for metastatic OS? In this aim we will use pediatric tumor samples to validate whether ABC can be used as a prognostic marker of OS progression. This will facilitate risk stratification of OS that is aggressive/metastatic in nature. Aim 3: How does ABC promotes OS progression? This aim will help us understand the mechanism by which ABC regulates OS progression. This will inform the identification of molecular targets that can be used for the development of novel drugs/therapeutic strategies to limit OS progression.