Mathematical Models of Cancer Cell Plasticity.

Quantitative modelling is increasingly important in cancer research, helping to integrate myriad diverse experimental data into coherent pictures of the disease and able to discriminate between competing hypotheses or suggest specific experimental lines of enquiry and new approaches to therapy. Here, we review a diverse set of mathematical models of cancer cell plasticity (a process in which, through genetic and epigenetic changes, cancer cells survive in hostile environments and migrate to more favourable environments, respectively), tumour growth, and invasion. Quantitative models can help to elucidate the complex biological mechanisms of cancer cell plasticity. In this review, we discuss models of plasticity, tumour progression, and metastasis under three broadly conceived mathematical modelling techniques: discrete, continuum, and hybrid, each with advantages and disadvantages. An emerging theme from the predictions of many of these models is that cell escape from the tumour microenvironment (TME) is encouraged by a combination of physiological stress locally (e.g., hypoxia), external stresses (e.g., the presence of immune cells), and interactions with the extracellular matrix. We also discuss the value of mathematical modelling for understanding cancer more generally.