Modelling the effects of cell-cycle heterogeneity on the response of a solid tumour to chemotherapy: biological insights from a hybrid multiscale cellular automaton model

Journal of Theoretical Biology
Gibin G PowathilMark A J Chaplain

Abstract

The therapeutic control of a solid tumour depends critically on the responses of the individual cells that constitute the entire tumour mass. A particular cell's spatial location within the tumour and intracellular interactions, including the evolution of the cell-cycle within each cell, has an impact on their decision to grow and divide. They are also influenced by external signals from other cells as well as oxygen and nutrient concentrations. Hence, it is important to take these into account when modelling tumour growth and the response to various treatment regimes ('cell-kill therapies'), including chemotherapy. In order to address this multiscale nature of solid tumour growth and its response to treatment, we propose a hybrid, individual-based approach that analyses spatio-temporal dynamics at the level of cells, linking individual cell behaviour with the macroscopic behaviour of cell organisation and the microenvironment. The individual tumour cells are modelled by using a cellular automaton (CA) approach, where each cell has its own internal cell-cycle, modelled using a system of ODEs. The internal cell-cycle dynamics determine the growth strategy in the CA model, making it more predictive and biologically relevant. It a...Continue Reading

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Related Concepts

Metabolic Process, Cellular
In Silico
Tumor Cells, Uncertain Whether Benign or Malignant
Biochemical Pathway
Antineoplastic Agents
Dioxygen
PLK1 gene
VHL protein, human
Extracellular
Angiogenic Process

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