Speaker: James Greene

Clarkson University
Potsdam, NY


Title: Induced drug resistance in cancer: modeling and control


Abstract: Drug resistance in cancer chemotherapy is a major cause of treatment failure. The origins of resistance are complex: the resistant phenotype may be present before treatment is initiated (pre-existing), or may be acquired during the course of therapy. Pre-existing resistance is thought to be driven primarily by genetic alterations, but acquired resistance is more complex: does the resistant subpopulation arise spontaneously (genetically or via phenotype-switching), or is it induced by the drug itself? Such questions are difficult to answer, but the consequences may be profound in a clinical setting. In this talk, we present recent work, both mathematical and experimental, on understanding the origins of drug resistance, with special emphasis placed on the more prominent role induced resistance appears to be playing in recent literature. Minimal mathematical models are introduced, and are used to demonstrate that the ability of a drug to promote resistance may have a significant impact on optimal therapy design. Current work towards integrating such models with experimental data is also discussed, including notions of both structural and practical identifiability, and further questions relating to the scheduling of multiple chemotherapies are posed.