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Systems BiologybioRxiv
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Assessment of patient-specific efficacy of chemo- and targeted-therapies: a micropharmacology approach

Aleksandra M. KarolakiD, Branton Huffstutler, Zain Ahmad KhaniD, Katarzyna Anna RejniakiD

Abstract

Both targeted and standard chemotherapy drugs are subject to various intratumoral barriers that impede their effectiveness. The tortuous vasculature, dense and fibrous extracellular matrix, irregular cellular architecture, and nonuniform expression of cell membrane receptors hinder drug molecule transport and perturb its cellular uptake. In addition, tumor microenvironments undergo dynamic spatio-temporal changes during tumor progression and treatment, which can also obstruct drug efficacy. To examine these aspects of drug delivery on a cell-to-tissue scale (single-cell pharmacology), we developed the microPKPD models and coupled them with patient-specific data to test personalized treatments.

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