The four variables,
hypoxia, acidity, high
glutathione (GSH) concentration and fast reducing rate (redox) are distinct and varied characteristics of solid
tumors compared to normal tissue. These parameters are among the most significant factors underlying the metabolism and physiology of solid
tumors, regardless of their type or origin. Low
oxygen tension contributes to both inhibition of
cancer cell proliferation and therapeutic resistance of
tumors; low extracellular pH, the reverse of normal cells, mainly enhances
tumor invasion; and dysregulated GSH and redox potential within
cancer cells favor their proliferation. In fact,
cancer cells under these microenvironmental conditions appreciably alter
tumor response to cytotoxic anti-
cancer treatments. Recent experiments measured the in vivo longitudinal data of these four parameters with
tumor development and the corresponding presence and absence of
tumor macrophage HIF-1α or HIF-2α in a mouse model of
breast cancer. In the current paper, we present a mathematical model-based system of (ordinary and partial) differential equations to monitor
tumor growth and susceptibility to standard
chemotherapy with
oxygen level, pH, and intracellular GSH concentration. We first show that our model simulations agree with the corresponding experiments, and then we use our model to suggest treatments of
tumors by altering these four parameters in tumor microenvironment. For example, the model qualitatively predicts that GSH depletion can raise the level of
reactive oxygen species (ROS) above a toxic threshold and result in inhibition of
tumor growth.