Combination therapeutics of Nilotinib and radiation in Acute Lymphoblastic Leukemia as an effective method against drug resistance

Abstract

In this work we combine in vitro experimentation with mathematical modeling to study the combined effect of the tyrosine kinase inhibitor nilotinib and ionizing radiation on acute lymphoblastic leukemia cells. We develop a mathematical model for the cell response to this combined therapy. This mathematical model is parameterized via cell viability experiments conducted at a variety of different levels of nilotinib concentration and radiation exposure. We use this parameterized mathematical model to predict cell viability at new levels of nilotinib concentration. These predictions are then compared with new sets of cell viability experiments. We then investigate the structure of optimal radiation dosing schedules under our mathematical model. Finally, the model is expanded to incorporate an additional toxicity constraint on healthy lymphoblast cells, further characterizing optimized treatment protocols.