Cancer is known as one of the leading causes of death in the world with difficult diagnose at early stages, poor prognosis and high mortality. Animal-based experiments and clinical trials have always been the main approach for cancer research, albeit they may have limitations and ethical issues. Mathematicalmodeling as an efficient method is used to predict results, optimize experimental design and reduce animal use. Our work focuses on the phenomenological simulation of cancer progression and therapies at the cell scale level.@en

Cell migration, known as an orchestrated movement of cells, is crucially important for wound healing, tumor growth, immune response as well as other biomedical processes. This paper presents a cell-based model to describe cell migration in non-isotropic fibrin networks around pancreatic tumor islets. This migration is determined by the mechanical strain energy density as well as cytokines-driven chemotaxis. Cell displacement is modeled by solving a large system of ordinary stochastic differential equations where the stochastic parts result from random walk. The stochastic differential equations are solved by the use of the classical Euler–Maruyama method. In this paper, the influence of anisotropic stromal extracellular matrix in pancreatic tumor islets on T-lymphocytes migration in different immune systems is investigated. As a result, tumor peripheral stromal extracellular matrix impedes the immune response of T-lymphocytes through changing direction of their migration.@en

Oncolytic virotherapy is known as a new treatment to employ less virulent viruses to specifically target and damage cancer cells. This work presents a cellular automata model of oncolytic virotherapy with an application to pancreatic cancer. The fundamental biomedical processes (like cell proliferation, mutation, apoptosis) are modeled by the use of probabilistic principles. The migration of injected viruses (as therapy) is modeled by diffusion through the tissue. The resulting diffusion–reaction equation with smoothed point viral sources is discretized by the finite difference method and integrated by the IMEX approach. Furthermore, Monte Carlo simulations are done to quantitatively evaluate the correlations between various input parameters and numerical results. As we expected, our model is able to simulate the pancreatic cancer growth at early stages, which is calibrated with experimental results. In addition, the model can be used to predict and evaluate the therapeutic effect of oncolytic virotherapy.@en

Cell migration plays an essential role in cancer metastasis. In cancer invasion through confined spaces, cells must undergo extensive deformation, which is a capability related to their metastatic potentials. Here, we simulate the deformation of the cell and nucleus during invasion through a dense, physiological microenvironment by developing a phenomenological computational model. In our work, cells are attracted by a generic emitting source (e.g., a chemokine or stiffness signal), which is treated by using Green’s Fundamental solutions. We use an IMEX integration method where the linear parts and the nonlinear parts are treated by using an Euler backward scheme and an Euler forward method, respectively. We develop the numerical model for an obstacle-induced deformation in 2D or/and 3D. Considering the uncertainty in cell mobility, stochastic processes are incorporated and uncertainties in the input variables are evaluated using Monte Carlo simulations. This quantitative study aims at estimating the likelihood for invasion and the length of the time interval in which the cell invades the tissue through an obstacle. Subsequently, the two-dimensional cell deformation model is applied to simplified cancer metastasis processes to serve as a model for in vivo or in vitro biomedical experiments.@en

More than eighty percent of pancreatic cancer involves ductal adenocarcinoma with an abundant desmoplastic extracellular matrix surrounding the solid tumor entity. This aberrant tumor microenvironment facilitates a strong resistance of pancreatic cancer to medication. Although various therapeutic strategies have been reported to be effective in mice with pancreatic cancer, they still need to be tested quantitatively in wider animal-based experiments before being applied as therapies. To aid the design of experiments, we develop a cell-based mathematical model to describe cancer progression under therapy with a specific application to pancreatic cancer. The displacement of cells is simulated by solving a large system of stochastic differential equations with the Euler–Maruyama method. We consider treatment with the PEGylated drug PEGPH20 that breaks down hyaluronan in desmoplastic stroma followed by administration of the chemotherapy drug gemcitabine to inhibit the proliferation of cancer cells. Modeling the effects of PEGPH20 + gemcitabine concentrations is based on Green’s fundamental solutions of the reaction–diffusion equation. Moreover, Monte Carlo simulations are performed to quantitatively investigate uncertainties in the input parameters as well as predictions for the likelihood of success of cancer therapy. Our simplified model is able to simulate cancer progression and evaluate treatments to inhibit the progression of cancer.@en

This paper presents a review of the role of mathematical modeling in investigating cancer progression, focusing on five models developed in our group. A brief overview of computational modeling progress is presented, followed by introduction of several mathematical formalisms (e.g., stochastic differential equations), numerical methods (e.g., finite element method, Green's functions, and combinations of time integration), and Monte Carlo simulations, which are currently used to quantify the underlying biomedical mechanisms, to approximate the results and to evaluate the impact of the input variables. Next, we provide specific examples of the computational models that we developed aimed at predicting the dynamics of the initiation and progression of cancer. Our simulation results show qualitative consistency with references and/or available experimental observations. Finally, perspectives are drawn on the possibilities of mathematical modeling for the prospects of cancer understanding and treatment therapies.@en

During metastasis of cancer, cell migration plays a crucial role, which is normally accompanied by morphological evolution. To simulate cell deformation, we develop a phenomenological, computational model involving deformation of a cell as well as its nucleus. The migration of a single cell is orchestrated by a generic signal (e.g. a chemokine or a stiffness stimulus), the microvascular flow and stochastic processes, which are dealt with by using Green’s Fundamental solutions, Poisseuille flow and a vector Wiener process, respectively. Moreover, due to the uncertainties in the input variables, Monte Carlo simulations are carried out to evaluate the correlations between various parameters and quantitatively predict the likelihood of vessel transmigration of one cell during cancer metastasis. @en

Mathematical modeling sheds light on cancer research. In addition to reducing animal-based experiments, mathematical modeling is able to provide predictions and prevalidate hypotheses quantitatively. In this work, two different agent-based frameworks regarding cancer modeling are summarised. In contrast, cell-based models focus on the behavior of every single cell and presents the interaction of cells on a small scale, whereas, cellular automata models are used to simulate the interaction of cells with their microenvironment on a large tissue scale.@en