A new MOX Report entitled “Mathematical modeling and sensitivity analysis of hypoxia-activated drugs” by Coclite, A; Montanelli Eccher, R.; Possenti, L.; Vitullo, P.; Zunino, P. has appeared in the MOX Report Collection.
Check it out here: https://www.mate.polimi.it/biblioteca/add/qmox/61-2025.pdf
Abstract: Hypoxia-activated prodrugs offer a promising strategy for targeting oxygen-deficient regions in solid tumors, which are often resistant to conventional therapies. However, modeling their behavior is challenging because of the complex interplay between oxygen availability, drug activation, and cell survival. In this work, we develop a multiscale and mixed-dimensional model that couples spatially resolved drug and oxygen transport with pharmacokinetics and pharmacodynamics to simulate the cellular response. The model integrates blood flow, oxygen diffusion, and consumption, drug delivery, and metabolism. To reduce computational cost, we mitigate the global nonlinearity by coupling the multiscale and mixed-dimensional models one-way with a reduced 0D model for drug metabolization. The global sensitivity analysis is then used to identify key parameters influencing drug activation and therapeutic outcome. This approach enables efficient simul! ation and supports the design of optimized therapies targeting hypoxia.
