A multi-scale agent-based model for avascular tumour growth

In this paper, we have developed a multi-scale, lattice-free, agent based model of avascular tumour growth in epithelial tissue. The model integrates different events to identify the underlying diversity within intracellular, cellular, and extracellular layer dynamics. The model considers every cell as an agent. A cellular agent may proliferate, spawns two identical daughter agents, or it may be transformed into other phenotypes during its life time depending on its internal proteins' activity as well as its external microenvironment. In this context, a simplified age-structured cell cycle model is adopted from the existing literature. The model considers that the intracellular events are regulated by p27 gene expression. In this model, p27 protein controls the overall tumour growth dynamics. Moreover, p27 is controlled by the external oxygen and nutrients that are modelled with the reaction-diffusion equations. The model also considers several biophysical forces which directly effect on the tumour growth dynamics. This modelling framework offers biologically realistic outcomes and also covers important criteria of the hallmarks of cancer which include oxygen and nutrient consumptions, micro-environmental heterogeneity, tumour cell proliferation by avoiding growth suppressor signals, replication of tumour cells at an abnormally faster rate, and resistance of apoptosis. The avascular tumour growth model is validated with immunohistochemistry and histopathology data. The outcome of the proposed model is very close to the range of the patient data, which concludes that the model is capable enough to mimic these complex biophysical phenomena.