Mathematical and computational models of drug transport in tumours

C. M. Groh, M. E. Hubbard, P. F. Jones, P. M. Loadman, N. Periasamy, B. D. Sleeman, S. W. Smye, C. J. Twelves, R. M. Phillips

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

The ability to predict how far a drug will penetrate into the tumour micro-environment 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.

Original languageEnglish
Article number20131173
Number of pages14
JournalJournal of the Royal Society Interface
Volume11
Issue number94
Early online date12 Mar 2014
DOIs
Publication statusPublished - 6 May 2014
Externally publishedYes

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Tumors
Theoretical Models
Pharmacokinetics
Pharmaceutical Preparations
Neoplasms
Drug delivery
Drug Administration Schedule
Cells
Blood vessels
Drug Administration Routes
Drug Design
Geometry
Computer Simulation
Blood Vessels
Clinical Trials
Experiments
Therapeutics

Cite this

Groh, C. M., Hubbard, M. E., Jones, P. F., Loadman, P. M., Periasamy, N., Sleeman, B. D., ... Phillips, R. M. (2014). Mathematical and computational models of drug transport in tumours. Journal of the Royal Society Interface, 11(94), [20131173]. https://doi.org/10.1098/rsif.2013.1173
Groh, C. M. ; Hubbard, M. E. ; Jones, P. F. ; Loadman, P. M. ; Periasamy, N. ; Sleeman, B. D. ; Smye, S. W. ; Twelves, C. J. ; Phillips, R. M. / Mathematical and computational models of drug transport in tumours. In: Journal of the Royal Society Interface. 2014 ; Vol. 11, No. 94.
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Groh, CM, Hubbard, ME, Jones, PF, Loadman, PM, Periasamy, N, Sleeman, BD, Smye, SW, Twelves, CJ & Phillips, RM 2014, 'Mathematical and computational models of drug transport in tumours', Journal of the Royal Society Interface, vol. 11, no. 94, 20131173. https://doi.org/10.1098/rsif.2013.1173

Mathematical and computational models of drug transport in tumours. / Groh, C. M.; Hubbard, M. E.; Jones, P. F.; Loadman, P. M.; Periasamy, N.; Sleeman, B. D.; Smye, S. W.; Twelves, C. J.; Phillips, R. M.

In: Journal of the Royal Society Interface, Vol. 11, No. 94, 20131173, 06.05.2014.

Research output: Contribution to journalArticle

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Groh CM, Hubbard ME, Jones PF, Loadman PM, Periasamy N, Sleeman BD et al. Mathematical and computational models of drug transport in tumours. Journal of the Royal Society Interface. 2014 May 6;11(94). 20131173. https://doi.org/10.1098/rsif.2013.1173