Since cancer is a complex phenomenon that incorporates events occurring on different length and time scales, therefore multiscale models are needed if we hope to adequately address cancer specific questions. In this paper we present three different multiscale individual-cell-based models, each motivated by cancer-related problems emerging from each of the spatial scales: extracellular, cellular or subcellular, but also incorporating relevant information from other levels. We apply these hybrid models to investigate the influence of the microenvironement on tumour invasion, cell-cell collaboration and competition leading to the initiation and growth of epithelial tumours, and to evolution of cell phenotypes/genotypes arising in tumours growing in different oxygen concentrations. We also discuss how these models relate to one another and can be used to bridge biological scales relevant to cancer.

Mathematical models of tumour spheroids, proposed since the early seventies, have been generally formulated in terms of a single diffusive nutrient which is critical for cell replication and cell viability. Only recently, attempts have been made to incorporate in the models the cell energy metabolism, by considering the interplay between glucose, oxygen and lactate (or pH). By assuming glucose and lactate as the only fuel substrates, we propose a simple model for the cell ATP production which takes into account the main reactions that occur in the glycolytic and the oxidative pathway. Under the assumption that cell death occurs when ATP production falls below a critical level, we have studied the free boundary problem for the concentration of glucose, lactate and oxygen inside the spheroid viable rim. We show that the existence of a necrotic core is guaranteed for a sufficiently large size of the spheroid.

Despite recent advances, treatment of patients with aggressive Non-Hodgkin's lymphoma (NHL2) has yet to be optimally designed. Notwithstanding the contribution of molecular treatments, intensification of chemotherapeutic regimens may still be beneficial. Hoping to aid in the design of intensified chemotherapy, we put forward a mathematical and computational model that analyses the effect of Doxorubicin on NHL over a wide range of patho-physiological conditions. The model represents tumour growth both in diffusion-limited settings, that is, in small avascular tumours and tumour cords, and in perfusion-limited settings, e.g. in well-vascularized tumours. Model simulations indicated the presence of a critical regimen intensity below which treatment will fall short of tumour elimination. Taking this critical intensity into account, we compared two regimen intensification strategies: Dose escalation and regimen densification, i.e. reducing the inter-dosing interval. In the diffusion-limited setting, dose escalation was somewhat more efficient than regimen densification. In the perfusion-limited setting, both intensification strategies yielded similar results. The present study coupled with a realistic myelotoxicity model may add insight on the optimisation of NHL intensified chemotherapy design.

A model of tumor growth in a spatial environment is analyzed. The model includes proliferating and quiescent compartments of tumor cells indexed by successively mutated cell phenotypes of increasingly proliferative aggressiveness. The model incorporates spatial dependence due to both random motility and directed movement haptotaxis. The model structures tumor cells by both cell age and cell size. The model consists of a system of nonlinear partial differential equations for the compartments of tumor cells, extracellular matrix, matrix degradative enzyme, and oxygen. The existence, uniqueness, positivity, regularity, and growth characteristics of the solutions are investigated.

In this paper we propose a mathematical model to describe the evolution of leukemia in the bone marrow. The model is based on a reaction-diffusion system of equations in a porous medium. We show the existence of two stationary solutions, one of them corresponds to the normal case and another one to the pathological case. The leukemic state appears as a result of a bifurcation when the normal state loses its stability. The critical conditions of leukemia development are determined by the proliferation rate of leukemic cells and by their capacity to diffuse. The analytical results are confirmed and illustrated by numerical simulations.

We study the mathematical properties of a general model of cell division structured with several internal variables. We begin with a simpler and specific model with two variables, we solve the eigenvalue problem with strong or weak assumptions, and deduce from it the long-time convergence. The main difficulty comes from natural degeneracy of birth terms that we overcome with a regularization technique. We then extend the results to the case with several parameters and recall the link between this simplified model and the one presented in [6]; an application to the non-linear problem is also given, leading to robust subpolynomial growth of the total population.

A mathematical model of the tumour growth along a blood vessel is proposed. The model employs the mixture theory approach to describe a tissue which consists of cells, extracellular matrix and liquid. The growing tumour tissue is supposed to be surrounded by the host tissue. Tumours where complete oxydation of glucose prevails are considered. Special attention is paid to consistent description of oxygen consumption and growth processes based on the energy balance. A finite difference numerical method is proposed. The level set method is used to track an interface between the tissues. The simulations show localization of the tumour within a limited distance from the vessels and constant expansion velocity along the vessels.