Models of Resistance in State-Structured Cancer Populations
Neuroblastoma is a pediatric brain cancer of variable clinical presentation. The causes behind the initiation, progression, and ultimate resistance of this cancer is unknown, though it is recognized that two cellular phenotypes underpin its deadliness: adrenergic (ADRN) and mesenchymal (MES). How these phenotypes influence the eco-evolutionary dynamics of neuroblastoma cell populations (especially under therapy) remains a mystery. This is due to the confusion surrounding whether the ADRN and MES phenotypes represent different cell types (species) or cell states (stages in the life cycle of a single species). This distinction is critical in understanding and ultimately treating neuroblastoma. In this talk, we will introduce theoretical methods to model the eco-evolutionary dynamics in state-structured neuroblastoma populations and use these models to tease apart cell type vs. cell state hypotheses. We will then expand and generalize this framework to continuous-structured models and discuss implications for cancer and bacterial resistance more generally.