Using systemic modeling and Bayesian calibration to investigate the role of the tumor microenvironment on chemoresistance

Using a novel modeling approach based on the so-called environmental stress level (ESL), we develop a mathematical model to describe systematically the collective influence of oxygen concentration and stiffness of the extracellular matrix on the response of tumor cells to a combined chemotherapeutic treatment. We perform Bayesian calibrations of the resulting model using particle filters, with in vitro experimental data for different hepatocellular carcinoma cell lines. The calibration results support the validity of our mathematical model. Furthermore, they shed light on individual as well as synergistic effects of hypoxia and tissue stiffness on tumor cell dynamics under chemotherapy.