Cancer is a multifactorial disease in which cell types lost their capability to regulate growth, proliferation, and cell death pathways, causing the uncontrolled proliferation of tumor cells. Cell death pathway is supported by the operation of the p53–Mdm2-negative feedback loop that has a central role to prevent the development of tumor cells. Under severe DNA damage, this loop takes the control of the apoptotic pathway and activates Bax, which, in turn, activates the caspase cascade to produce the death of the injured cell. However, events like Mdm2 overexpression or the suppression of caspase-9 gene can block the transmission of the death signal to the caspase cascade allowing the survival of the mutated cell. In this chapter, a mathematical model that explores the effect of Mdm2 overexpression and the suppression of caspase-9 on the control of death by the p53–Mdm2 loop is presented. From the model, two strategies for tumor cell survival are indentified, showing how mutations that affect the death pathway allow the survival of transformed cells. The model suggests that the combination of different simultaneous treatments against these mutations can be a suitable strategy against cancer.
Part of the book: Evolution of Ionizing Radiation Research