Grant: Project Grant - Priority Announcement: Pediatric Cancer Research

Osteosarcoma is the most common bone cancer and disproportionately affects children, adolescents and young adults. The use of surgery and high dose chemotherapy has brought osteosarcoma mortality down to 30%. When an osteosarcoma is found in other parts of the body such as the lungs or the liver, this means that the cancer has spread from its location in a bone, to a new site and formed a so called metastasis. People that have metastases already at the time of diagnosis have a very low odds to beat their disease. Similarly, patients who do not respond well to initial chemotherapy treatment may die of this of this cancer even if their disease is not initially metastatic. This cancer is characterized by extensive genetic alterations where large portions of the genome are shuffled from their original position, and in the process many genes are lost or gained. Our labs discovered that a significant portion of osteosarcoma cases also have alterations in how genes function beyond the simple loss or gain of genetic material, this is a process called epigenetic regulation. In this proposal we aim to understand the mechanism by which epigenetic alterations contribute to osteosarcoma development and resistance to treatment. We will use models based on human cells and mouse models to perturb epigenetic mechanisms and understand their effect on osteosarcoma tumors.