Targeting Beta-Catenin Mediated Activity in Metastatic Osteosarcoma

Baylor College of Medicine, Houston, TX

Metastatic disease, which is when the cancer has spread throughout the body, is responsible for about 90% of all cancer-related deaths. For children afflicted with metastatic osteosarcoma, the most common bone tumor in the pediatric population, it often means a very aggressive cancer that is associated with an extremely poor outcome. Unfortunately, one reason for this unacceptable outcome is due to our lack of understanding the biology of the metastatic state and identifying better treatment options.

Recently our laboratory has created a new mouse model of metastatic osteosarcoma (OS) that mimics the human tumor development and progression. Using the tumors from this model, we have been able to analyze genes and determine pathways that are functioning abnormally, including the identification of key alterations within metastatic tumors in a key pathway in the cell known as the Wnt cascade.

Our proposal will continue to investigate the exact role of Wnt signaling during metastatic development, or evolution, through both innovative pre-clinical models as well as functional and therapeutic studies. Furthermore, using these models we will test a new therapeutic agent designed to target this pathway that one day can be brought to the clinical care of these patients. Therefore, by gaining a better understanding of the detailed role of Wnt signaling during metastatic development, we will elucidate novel molecular aberrations and further identification of novel therapies.