Mathematical modeling of radioresistance and radioleukemogenesis

Abstract

In this thesis we study the effects of ionizing radiation exposure on the apparent development of radioresistant cancer cells (part 1) and the development of leukemia (part 2). In part 1 we present our research on recent findings that cancer cells possibly develop a form of radioresistance during radiotherapy. Based on mathematical modeling and experiments, we conclude that, although cancer cells seem to develop a form of radioresistance in experiments, it is unlikely that this is actually the case. Thus, the previously observed supposed radioresistance phenomenon will probably not influence the efficacy of radiotherapy.

In part 2 of this thesis, we study the relationship between radiation dose and acute myeloid leukemia (AML) incidence. All individuals are constantly exposed to very low doses of ionizing radiation and the effect of these doses on the cancer incidence is unknown/uncertain. Hence, it is important to utilize a model to relate the radiation dose to a risk of developing cancer. Because a linear dose-risk model is typically utilized, it is possible that the true cancer risk is overestimated at very low doses if the true dose-risk relationship is nonlinear. We have developed a mechanistic AML model to quantify the possible relationship between radiation dose and AML incidence. We found that, although the use of a linear model results in an overestimation of the modeled nonlinear low-dose AML incidence, it is possible to correct for this overestimation. Our mathematical modeling work illustrates how one can translate biological knowledge of a disease into a mathematical model.