Groh, Christian M., Hubbard, Matthew E., Jones, Pamela F., Loadman, Paul M., Periasamy, Raj, Sleeman, Brain D., Smye, Steven W., Twelves, Chris J. and Phillips, Roger M. (2014) Mathematical and computational models of drug transport in tumours. Interface: Journal of the Royal Society, 11 (94). p. 1173. ISSN 1742-5662

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 direc- tly 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 mechan- isms 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 trans- port modelling tool for informing strategies for the treatment of tumour cells which are ‘pharmacokinetically resistant’ to chemotherapeutic strategies.

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