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Kinetic modelling of the role of the aldehyde dehydrogenase enzyme and the breast cancer resistance protein in drug resistance and transport

Atari, M. I., Chappell, M. J., Errington, Rachel Jane ORCID: https://orcid.org/0000-0002-8016-4376, Smith, Paul James and Evans, N. D. 2011. Kinetic modelling of the role of the aldehyde dehydrogenase enzyme and the breast cancer resistance protein in drug resistance and transport. Computer Methods and Programs in Biomedicine 104 (2) , pp. 93-103. 10.1016/j.cmpb.2010.06.008

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Abstract

A compartmental model for the in vitro uptake kinetics of the anti-cancer agent topotecan (TPT) has been extended from a previously published model. The extended model describes the drug activity and delivery of the pharmacologically active form to the DNA target as well as the catalysis of the aldehyde dehydrogenase (ALDH) enzyme and the elimination of drug from the cytoplasm via the efflux pump. Verification of the proposed model is achieved using scanning-laser microscopy data from live human breast cancer cells. Before estimating the unknown model parameters from the experimental in vitro data it is essential to determine parameter uniqueness (or otherwise) from this imposed output structure. This is formally performed as a structural identifiability analysis, which demonstrates that all of the unknown model parameters are uniquely determined by the output structure corresponding to the experiment.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
R Medicine > RM Therapeutics. Pharmacology
Uncontrolled Keywords: Efflux pump; Drug kinetics; Topotecan; Aldehyde dehydrogenase; Structural identifiability; Parameter estimation
Publisher: Elsevier
ISSN: 0169-2607
Last Modified: 21 Oct 2022 09:38
URI: https://orca.cardiff.ac.uk/id/eprint/37120

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