Mathematical modeling and sensitivity analysis of hypoxia-activated drugs
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arXiv
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| Hauptverfasser: | , , , , |
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| Format: | Preprint |
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2025
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| _version_ | 1866909822335582208 |
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| author | Coclite, Alessandro Eccher, Riccardo Montanelli Possenti, Luca Vitullo, Piermario Zunino, Paolo |
| author_facet | Coclite, Alessandro Eccher, Riccardo Montanelli Possenti, Luca Vitullo, Piermario Zunino, Paolo |
| contents | 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 through a one-way coupling of the multiscale and mixed/dimensional models with a reduced 0D model for the drug metabolism. The global sensitivity analysis is then used to identify key parameters influencing drug activation and therapeutic outcome. This approach enables efficient simulation and supports the design of optimized hypoxia-targeted therapies. |
| format | Preprint |
| id |
arxiv_https___arxiv_org_abs_2507_15642 |
| institution | arXiv |
| publishDate | 2025 |
| record_format | arxiv |
| spellingShingle | Mathematical modeling and sensitivity analysis of hypoxia-activated drugs Coclite, Alessandro Eccher, Riccardo Montanelli Possenti, Luca Vitullo, Piermario Zunino, Paolo Numerical Analysis 92C50, 92C45, 35Q92, 35R20, 65M60 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 through a one-way coupling of the multiscale and mixed/dimensional models with a reduced 0D model for the drug metabolism. The global sensitivity analysis is then used to identify key parameters influencing drug activation and therapeutic outcome. This approach enables efficient simulation and supports the design of optimized hypoxia-targeted therapies. |
| title | Mathematical modeling and sensitivity analysis of hypoxia-activated drugs |
| topic | Numerical Analysis 92C50, 92C45, 35Q92, 35R20, 65M60 |
| url | https://arxiv.org/abs/2507.15642 |