Osteosarcoma (OS) is the most common primary bone cancer. Cancer metastasis is the leading cause of cancer related deaths. A key factor in the metastatic process is the presence of proteolytic enzymes that contribute to the development of a vascular network, degrade the extracellular matrix, and increase the cell’s ability to invade. Our lab is specifically interested in a family of proteolytic enzymes called Cathepsins. Primarily, we are interested in Cathepsins L and K. In addition, to their roles in metastasis, recent studies have demonstrated that Cathepsins also play a role in cancel cell resistance to chemotherapy. This project will evaluate the role of cathepsin inhibition on the development and reversal of drug resistance in vitro. We believe that decreasing CTSL/CTSK will increase the efficacy of current chemotherapeutics and improve overall survival for OS patients.