Funded by the Constellation Gold Network Distributors in honor of the Dick Vitale Fund
Alveolar rhabdomyosarcoma (ARMS) is an aggressive cancer of the muscle that occurs in young children and teenagers. Despite years of attempts to improve chemotherapy regimens, survival of patients with ARMS remains poor. This is especially true for patients who have advanced disease at the time of diagnosis. ARMS tumors typically possess a single and defining genetic mutation. A break in one specific chromosome will fuse with another chromosome, creating a fusion gene. These fusion genes can control hundreds or even thousands of other genes and transform a normal cell into a cancer cell. My project focuses on the PAX3-FOXO1 fusion. This fusion causes the most severe form of ARMS. However, there are no therapies that target PAX3-FOXO1 directly. Our goal is to understand how PAX3-FOXO1 transforms a normal cell into a cancer cell so that we can find new and precise therapies. To study this, we use zebrafish as a disease model because they are genetically similar to humans. We will integrate the human PAX3-FOXO1 fusion gene into the zebrafish genome to determine the steps required for ARMS tumor formation. For example, often normal development is hijacked by cancer genes. Our studies will determine if and how this happens in ARMS. Directly comparing zebrafish and human ARMS will pinpoint the most important drivers of disease and likely find new options for more targeted and specific therapies.