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.
Acknowledgements
TA would like to thank the EPSRC for financial support under grant GR/509067.
Notes
This means that, as far as our model is concerned, regions occupied by quiescent cells can be identified with hypoxic regions.
For a discussion of what is meant by the local VEGF concentration of a vessel, see [Citation3].
In fact, this combination is far from optimal as the damage it produces to the host normal tissue is massive. However, in the present study, we ignore this fact as we do not intend to carry out a thorough analysis of therapeutical protocols. Instead, this is a proof of concept exercise as to whether our model is able to capture the essential features observed in experiments.