Grant: Banting Postdoctoral Fellowship Program

Cancer is the leading cause of death in Canada. About 1 in 2 Canadians will be diagnosed with cancer, and 1 in 4 will die from the disease. Despite major progress in our understanding of cancer biology, more than 80% of patients suffering from lung, pancreatic, esophageal and liver cancer still die within 5 years of diagnosis. Oncolytic viruses are cancer-killing therapeutics that selectively infect and kill cancer cells, while leaving healthy cells unharmed. Although clinical trials testing these therapies have shown promising results over the last 25 years, only 30 percent of patients show objective responses to these therapies and resistance is common. These observations have led some to suggest that oncolytic viruses should be combined with other anti-cancer treatments to improve outcomes. Our research group and others have recently discovered that the Hippo signaling pathway plays important roles in multiple cancer hallmarks such as cell proliferation, angiogenesis, the immune checkpoint, and metastasis. These features make the Hippo pathway an attractive candidate for targeting during cancer treatments. This project aims to, for the first time, combine oncolytic viruses and pharmacological targeting of the Hippo signaling pathway. Since the Hippo pathway affects many of the processes that contribute to the efficacy of oncolytic viruses (e.g. immune cell behaviour, angiogenesis), there is a rationale for combining these two modalities of treatment. This combination therapy will likely increase treatment efficiency and dramatically reduce the chance of resistance. In this project, I will use patient-derived tumor cells to measure the efficiency of this combined therapeutic. In doing so, we hope to test a new therapeutic strategy for successful cancer treatment.