Morgan Craig (University of Montreal)
Tuesday November 26, 12-1pm
McIntyre Medical Building, Room 1034
"Quantitative approaches addressing intratumour heterogeneity and its impact on therapeutic outcomes"
Abstract: Typically, two primary forms of intratumour heterogeneity (ITH) are studied, intrinsic and acquired, both affecting the cause and the progression of disease. Indeed, the dramatic range of genetic and phenotypic diversity that is conferred during tumour evolution, comprising both passenger and driver mutations, is an underlying driver of acquired resistance that can significantly impact therapeutic responses and sensitivities to new, more targeted agents. However, other factors influencing ITH warrant investigation as they can play a major role in determining treatment efficacy and overall outcomes.
In this talk, I will discuss how ITH in terms of phenotypic and proliferative heterogeneity impacts on therapeutic responses. The first part will focus on Cooperative Adaptation to Therapy (CAT) in heterogenous non-small cell lung cancer. CAT is a phenomenon where drug-sensitive cancer cells with different genetic and phenotypic features within a 3-dimensional heterogeneous tumour induce non-mutational resistance in their neighbouring cells under pressure of cancer therapy. Using an in silico clinical trial approach, I will then discuss how to leverage cell cycle heterogeneity in late-stage melanoma to individualize and optimize combination oncolytic virus immunotherapy protocols to improve patient outcomes. These two recent studies highlight our work to understand pathophysiological mechanisms and patterns to rationally improve therapeutic strategies and provide clinically-actionable treatment designs.