Mathematical and computational models of drug transport in tumours
Groh, C.M. Hubbard, M.E. Jones, P.F. Periasamy, Nagarajan Sleeman, B.D. Smye, S.W. Twelves, Christopher J. Phillips, Roger M.
Groh, C.M.
Hubbard, M.E.
Jones, P.F.
Periasamy, Nagarajan
Sleeman, B.D.
Smye, S.W.
Twelves, Christopher J.
Phillips, Roger M.
Publication Date
2014-05-06
End of Embargo
Supervisor
Rights
Peer-Reviewed
Yes
Open Access status
closedAccess
Accepted for publication
2014-02-20
Institution
Department
Awarded
Embargo end date
Collections
Additional title
Abstract
The ability to predict how far a drug will penetrate into the tumour microenvironment
within its pharmacokinetic (PK) lifespan would provide
valuable information about therapeutic response. As the PK profile is directly
related to the route and schedule of drug administration, an in silico tool
that can predict the drug administration schedule that results in optimal
drug delivery to tumours would streamline clinical trial design. This paper
investigates the application of mathematical and computational modelling
techniques to help improve our understanding of the fundamental mechanisms
underlying drug delivery, and compares the performance of a simple
model with more complex approaches. Three models of drug transport are
developed, all based on the same drug binding model and parametrized by
bespoke in vitro experiments. Their predictions, compared for a ‘tumour
cord’ geometry, are qualitatively and quantitatively similar. We assess the
effect of varying the PK profile of the supplied drug, and the binding affinity
of the drug to tumour cells, on the concentration of drug reaching cells and the
accumulated exposure of cells to drug at arbitrary distances from a supplying
blood vessel. This is a contribution towards developing a useful drug transport
modelling tool for informing strategies for the treatment of tumour
cells which are ‘pharmacokinetically resistant’ to chemotherapeutic strategies.
Version
No full-text in the repository
Citation
Groh CM, Hubbard ME, Jones PF et al (2014) Mathematical and computational models
of drug transport in tumours. Journal of the Royal Society Interface. 11(94)
Link to publisher’s version
Link to published version
Link to Version of Record
Type
Article