Over the past decade or so, there have been a large number of modelling approaches aimed
at elucidating the most important mechanisms affecting the formation of new capillaries
from parent blood vessels — a process known as angiogenesis. Most studies have focussed
upon the way in which capillary sprouts are initiated and migrate in response to
diffusible chemical stimuli supplied by hypoxic stromal cells and leukocytes in the
contexts of solid tumour growth and wound healing. However, relatively few studies have
examined the important role played by blood perfusion during angiogenesis and fewer still
have explored the ways in which a dynamically evolving vascular bed architecture can
affect the distribution of flow within it. From the perspective of solid tumour growth
and, perhaps more importantly, its treatment (e.g. chemotherapy), it would clearly be of
some benefit to understand this coupling between vascular structure and perfusion more
fully. This paper focuses on the implications of such a coupling upon chemotherapeutic,
anti-angiogenic, and anti-vascular treatments.
In an extension to previous work by the authors, the issue of pericyte recruitment during
vessel maturation is considered in order to study the effects of different anti-vascular
and anti-angiogenic therapies from a more rigorous modelling standpoint. Pericytes are a
prime target for new vascular disrupting agents (VDAs) currently in clinical trials.
However, different compounds attack different components of the vascular network and the
implications of targeting only certain elements of the capillary bed are not immediately
clear. In light of these uncertainties, the effects of anti-angiogenic and anti-vascular
drugs are re-examined by using an extended model that includes an interdependency between
vessel remodelling potential and local pericyte density. Two- and three-dimensional
simulation results are presented and suggest that it may be possible to identify a
VDA-specific “plasticity window” (a time period corresponding to low pericyte density),
within which a given VDA would be most effective.