Grant: Doctoral Research Award: Canada Graduate Scholarships

Synovial sarcoma is an aggressive soft tissue cancer primarily affecting adolescents and young adults and has a 5-year survival rate of 15% with disseminated disease. Synovial sarcoma is caused by a specific mutation-fusion of the SS18 gene to the SSX gene-producing a new protein, SS18SSX. Understanding the effects of SS18SSX is key to uncovering the underlying pathogenesis of synovial sarcoma and developing better therapies. By genetically engineering mouse connective tissue stem cells to produce SS18SSX, we created a novel mouse model to study synovial sarcoma that closely recapitulates the disease seen in humans. All mutant mice develop synovial sarcoma at 15 to 16 weeks of age, demonstrating the reproducibility and the strong effects of this mutation. As we can detect and analyze mouse cells throughout the course of tumor development, this model can reveal vulnerabilities based on the signals this cancer relies on to form, grow, and spread. Our model and previous literature have identified Wnt signaling as one key pathway activated by SS18SSX. Wnt signaling allows cells to proliferate, invade surrounding tissue, and metastasize by disrupting the bonds that normally connect cells to other cells. Thus, we will investigate how using drugs to block Wnt signaling affects the ability of SS18SSX to drive cancer progression. We will treat mice with drugs which have passed phase one clinical trials for safety and efficacy to inhibit Wnt and look for changes in tumor growth, invasiveness, metastatic spread, and mouse survival. With these investigations, we can evaluate the feasibility of treating synovial sarcoma with drug inhibitors of Wnt, gain a better understanding of cancer development, and inform the development of new and effective therapies.