Computational and Mathematical Methods in Medicine
Volume 7 (2006), Issue 2-3, Pages 85-119
doi:10.1080/10273660600968994

Multiscale Modelling of Tumour Growth and Therapy: The Influence of Vessel Normalisation on Chemotherapy

Tomás Alarcón,1 Markus R. Owen,2 Helen M. Byrne,2 and Philip K. Maini3

1Bioinformatics Unit, Department of Computer Science, University College London, Gower Street, London WC1E 6BT, UK
2School of Mathematical Sciences, Centre for Mathematical Medicine, University of Nottingham, Nottigham NG7 2RD, UK
3Mathematical Institute, Centre for Mathematical Biology, University of Oxford, 24-29 St Giles', Oxford OX1 3LB, UK

Received 11 June 2006; Accepted 14 July 2006

Copyright © 2006 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Following the poor clinical results of antiangiogenic drugs, particularly when applied in isolation, tumour biologists and clinicians are now turning to combinations of therapies in order to obtain better results. One of these involves vessel normalisation strategies. In this paper, we investigate the effects on tumour growth of combinations of antiangiogenic and standard cytotoxic drugs, taking into account vessel normalisation. An existing multiscale framework is extended to include new elements such as tumour-induced vessel dematuration. Detailed simulations of our multiscale framework allow us to suggest one possible mechanism for the observed vessel normalisation-induced improvement in the efficacy of cytotoxic drugs: vessel dematuration produces extensive regions occupied by quiescent (oxygen-starved) cells which the cytotoxic drug fails to kill. Vessel normalisation reduces the size of these regions, thereby allowing the chemotherapeutic agent to act on a greater number of cells.