Grant: Operating Grant - PA: Regional Partnership Program - Newfoundland and Labrador

Oncolytic viruses are engineered or naturally occurring viruses that replicate in cancer cells, but not in normal cells. They have become a focus of attention for cancer therapy in recent years as clinical studies have shown them to be quite promising. However, the biochemical mechanisms of their tumor selectivity still remain to be studied. In this proposal, we will investigate how one of the oncogenic cell signaling pathways, Ras/MEK, promotes the replication of certain oncolytic viruses in cancer cells. We believe that the Ras/MEK pathway inhibits function of a cellular protein known as interferon regulatory factor (IRF)-1, which is known to block viral replication, resulting in efficient replication of oncolytic viruses in cancer cells. Our study will provide a novel insight into the molecular mechanisms of viral oncolysis as well as the future development of new oncolytic viruses with improved efficacy and safety.