Grant: Doctoral Research Award: Canada Graduate Scholarships

Ewing Sarcoma (ES) is a rare, highly aggressive cancer that occurs in soft tissue and bone that primarily affects children and young adults. When ES has spread to other organs, the survival rate is about 20%, showing a need to develop better treatments to combat this aggressive disease. A class of drug called PARP inhibitors was predicted to be effective against ES, however, it was unsuccessful in clinical trials. Studies have shown that better outcomes can be reached by combining PARP inhibitors with another drug called HDAC inhibitors. Combining two different drugs, however, raises concerns about compatibility in the body which may result in toxicities for the patient. We are developing a drug that inhibits both PARP and HDAC at once to mitigate the side effects that traditional combination treatments would have. We currently use cell models and animal studies to study ES. However, cell models lack important elements that affect tumor growth and treatment response. Animal studies are controversial and may not accurately represent how treatments work in patients. With 3-D bioprinting, we can create a model that better represents the environment of human bone. Our initial model successfully grows ES cells and we will compare this model to existing tests to study how tumors respond to treatment. Preliminary results show that a drug from the kt-3000 series is ten times more effective than existing drugs in cell models. The drug causes cells to stop dividing and increases DNA damage, causing cancer cells to die. It also reduces cell growth in the lungs, a primary site of metastases for ES. We also need to understand how the drug affects cells and ensure it binds specifically to the right proteins. We are improving the drug's properties to enter it into clinical trials. Successful development of the bioprinted bone model will provide a better model for drug development and a novel drug will provide an improved treatment option for patients with aggressive disease.