A hybrid approach to multi-scale modelling of cancer.

In this paper, we review multi-scale models of solid tumour growth and discuss a middle-out framework that tracks individual cells. By focusing on the cellular dynamics of a healthy colorectal crypt and its invasion by mutant, cancerous cells, we compare a cell-centre, a cell-vertex and a continuum model of cell proliferation and movement. All models reproduce the basic features of a healthy crypt: cells proliferate near the crypt base, they migrate upwards and are sloughed off near the top. The models are used to establish conditions under which mutant cells are able to colonize the crypt either by top-down or by bottom-up invasion. While the continuum model is quicker and easier to implement, it can be difficult to relate system parameters to measurable biophysical quantities. Conversely, the greater detail inherent in the multi-scale models means that experimentally derived parameters can be incorporated and, therefore, these models offer greater scope for understanding normal and diseased crypts, for testing and identifying new therapeutic targets and for predicting their impacts