University of Minnesota
The aim of this work is to develop descriptive mathematical models for the localization of anti-cancer agents in solid tumor tissue and the subsequent intratumoral drug generation associated with two-step cancer chemotherapy. Equations governing the diffusion of large anti-cancer agents out of the vasculature and into the tumor are derived, analyzed, and numerically simulated. The effects of the tumor vasculature, binding kinetics, and administration schedule on the intratumoral conjugate concentration are investigated and the critical parameters that influence the localization and retention of the agent in the tumor are determined.
The model is then extended to include the dynamics of site specific drug generation. Theoretical analysis and numerical simulation are used to isolate critical parameters for increased drug generation and improved therapeutic index (TI) which measures the overall effectiveness of the targeting strategy.
Finally, the effects of certain barriers to chemotherapeutic treatments including vascular heterogeneity and radially outward convection are studied. Predictions made by the mathematical model can lead to improved treatment protocols for two step cancer chemotherapy.