Sensitivity analysis of cancer-killing virus models to improve therapeutic outcomes

Oncolytic viruses (OVs) are promising anti-tumour therapeutics that specifically infect and destroy cancer cells. Great effort is allocated to OVs in clinical trials, and to research in Canada and aboard that can further improve their therapeutic potential. To enhance the potential of OV-based cancer treatments, Drs. Kaern and Diallo use computational biology methods to identify potential strategies that can increase the cancer-specificity of OV and allow them to evade anti-viral defences. This approach analyzes mathematical models of interactions between viruses, normal and cancerous tissues, and immunity systems. This project focuses on identifying interactions that can be targeted by drugs to sensitize cancer cells to OV infection while leaving normal cells intact. This goal will be reached by conducting what in mathematics is known as a sensitivity analysis, which quantifies how much a model output (e.g., the rate of cell death) is affected by variation in model parameters (e.g., infection rates). The idea is that the parameters that are the most sensitive to variation are also the parameters that should be targeted to achieve optimal outcomes. We anticipate that the parameters identified by the proposed analysis will represent biological processes that can be targeted by therapeutic means. As cancer is the leading cause of death in the Canadian population, Dr. Diallo is committed to explore the feasibility of subsequent experiment testing of the model predictions. Even if no viable therapeutic strategy is identified, the proposed research will improve the understanding of the cause-effects relationships within an experimentally validated model of OV dynamics. As demonstrated in past collaborative work published by Drs. Kaern and Diallo in Nature Communications, these relationships have significant and direct implications for the design of novel OVs and for understanding how therapeutic outcomes can improve by combining OVs and drug treatment.