Selecting a differential equation cell cycle model for simulating leukemia treatment
File(s)
Author(s)
Type
Journal Article
Abstract
This manuscript studies three differential equation models of the leukemia cell cycle: a population balance model (PBM) using intracellular protein expression levels as state variables representing phase progress; a delay differential equation model (DDE) with temporal phase durations as delays; and an ordinary differential equation model (ODE) of inter-phase progression. In each type of model, global sensitivity analysis determines the most significant parameters while parameter estimation fits experimental data. In order to compare models based purely on the output of their structural properties, an expected behavior was defined, and each model was coupled to a pharmacokinetic/pharmacodynamic model of chemotherapy delivery. Results suggest that the particular cell cycle model chosen highly affects the simulated treatment outcome, given the same steady state kinetic parameters and drug dosage/scheduling. The manuscript shows how cell cycle models should be selected according to the complexity, sensitivity and parameter availability of the application envisioned.
Date Issued
2015-07-17
Date Acceptance
2015-07-17
Citation
Industrial & Engineering Chemistry Research, 2015, 54 (36), pp.8847-8859
ISSN
1520-5045
Publisher
ACS Publications
Start Page
8847
End Page
8859
Journal / Book Title
Industrial & Engineering Chemistry Research
Volume
54
Issue
36
Copyright Statement
© 2015 American Chemical Society. This document is the Accepted Manuscript version of a Published Work that appeared in final form in Industrial & Engineering Chemistry Research, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://dx.doi.org/10.1021/acs.iecr.5b01150
Publication Status
Published
Article Number
150717023650007