Multiscale Modelling of Colorectal Cancer
Existing models for tumour growth generally do not focus on any particular kind of cancer and concentrate on a single time and length scale. Moreover, as discussed above, existing modelling approaches to crypt dynamics and colorectal cancer are very simple, they also focus on a single level of organisation, and they are often useful for the particular purposes they were designed for only. Alternatively, we are building a multiscale model (Figure 5) for colorectal cancer that covers all levels of organisation from molecule to tissue. At the subcellular level, deterministic continuum models are used to describe biochemical networks involving Wnt signalling and cell cycle control. Spatially-dependent gene expression patterns and environmental conditions define the behaviour of the components of a cellular automaton model and, in particular, how they proliferate, migrate, differentiate and die. Finally, at the tissue level, the crypt's behaviour is determined by the integration of all the individual cell events with macroscale biomechanics and dynamics.
The advantages of a multiscale approach to colorectal cancer include the possibility to:
- Use experimental data concerning different levels of organisation.
- Investigate interactions between phenomena occurring at different levels.
- Test drugs on the system as a whole.
Figure 5: Schematic of the interactions and feed-back loops occurring between the different levels of organisation. Tissue components are represented in yellow, cellular components in green and subcellular components in blue. Each cell division implies a certain chance of replicative errors and, thereby, of permanent DNA damage. This chance is increased by the effect of external factors with carcinogenic potential.
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