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

  • Authors:

  • M. I. Atari;M. J. Chappell;R. J. Errington;P. J. Smith;N. D. Evans

  • Affiliations:

  • School of Engineering, University of Warwick, Coventry CV4 7AL, UK;School of Engineering, University of Warwick, Coventry CV4 7AL, UK;Department of Medical Biochemistry and Immunology, University of Wales College of Medicine, Cardiff University, Cardiff CF14 4XN, UK;Department of Pathology, University of Wales College of Medicine, Cardiff University, Cardiff CF14 4XN, UK;School of Engineering, University of Warwick, Coventry CV4 7AL, UK

  • Venue:
  • Computer Methods and Programs in Biomedicine
  • Year:
  • 2011

Quantified Score

Hi-index 0.00

Visualization

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.