An in silico hybrid continuum-/agent-based procedure to modelling cancer development: Interrogating the interplay amongst glioma invasion, vascularity and necrosis

This paper develops a three-dimensionalin silicohybrid model of cancer, which describes the multi-variate phenotypic behaviour of tumour and host cells. The model encompasses the role of cell migration and adhesion, the influence of the extracellular matrix, the effects of oxygen and nutrient availability, and the signalling triggered by chemical cues and growth factors. The proposedin silicohybrid modelling framework combines successfully the advantages of continuum-based and discrete methods, namely the finite element and agent-based method respectively. The framework is thus used to realistically model cancer mechano-biology in amultiscale fashion while maintaining the resolution power of each method in a computationally cost-effective manner. The model is tailored to simulate glioma progression, and is subsequently used to interrogate thebalance between the host cells and small sized gliomas, while the go-or-grow phenotype characteristic inglioblastomas is also investigated. Also, cell–cell and cell–matrix interactions are examined with respect to theireffect in (macroscopic) tumour growth, brain tissue perfusion and tumour necrosis. Finally, we use thein silico framework to assess differences between low-grade and high-grade glioma growth, demonstrating significant differences in the distribution of cancer as well as host cells, in accordance with reported experimental findings.