Speaker
Description
Elevated interstitial fluid pressure (IFP) and abnormal tumor vasculature limit the delivery of therapeutic agents to solid tumors. Although anti-angiogenic therapy can transiently normalize tumor vasculature and improve transport, the impact of treatment scheduling on IFP dynamics and drug delivery remains poorly understood. In this study, we develop a spatiotemporal multiphysics model that explicitly couples vascular normalization with interstitial transport to quantify how treatment scheduling modulates tumor transport barriers. The framework enables systematic comparison of intermittent, metronomic, and hybrid dosing strategies. It is formulated as a system of coupled nonlinear partial differential equations describing tumor growth, angiogenesis, interstitial fluid flow, and drug transport. Simulation results reveal that treatment scheduling strongly regulates tumor IFP and drug distribution, even when the cumulative drug dose is fixed. All regimens induce vascular normalization and reduce average tumor IFP by 51–57%, consistent with reported in vivo observations, with the largest reduction under metronomic therapy. When combined with intermittent chemotherapy, this strategy produces the highest intratumoral drug accumulation (AUC = 1.15) and the most uniform spatial distribution. These results highlight the strong dependence of drug transport on dosing frequency and administration timing, and provide a quantitative framework for optimizing combination therapy schedules.
