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| Pancreatic cancers contain significant amounts of stromal tissue that contributes to poor penetration of both metabolites and drug particles. As a result these tumors are hypoxic and standard therapeutic compounds show much lower efficacy in vivo then in laboratory experiments. To test optimal administration schedules of a novel class of drugs that are activated in the tumor hypoxic regions (HAPs, hypoxia-activated pro-drugs), as well as strategies to make the tumors more sensitive to these drugs, we developed a mechanistic computational model carefully parameterized with experimental data. This interdisciplinary approach has been used to investigate complex interplay between HAPs and tumor microenvironmental heterogeneity. We will present a current state of the computational model integrated with experimental data and calibrated to pancreatic tumor xenografts that aim on providing an analytical tool in designing drug properties and drug administration schedules that will optimize drug penetration into the tumor tissue and enhance their therapeutic efficacy. |
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