Emergence of Cytotoxic Resistance in Cancer Cell Populations: Single-cell Mechanisms and Population-level Consequences
Tommaso Lorenzi, Rebecca H Chisholm, Alexander Lorz, Annette K Larsen, Luis Neves de Almeida, Alexandre Escargueil, Jean Clairambault, T Simos (ed.), C Tsitouras (ed.)
PROCEEDINGS OF THE INTERNATIONAL CONFERENCE ON NUMERICAL ANALYSIS AND APPLIED MATHEMATICS 2015 (ICNAAM-2015) | AMER INST PHYSICS | Published : 2016
We formulate an individual-based model and a population model of phenotypic evolution, under cytotoxic drugs, in a cancer cell population structured by the expression levels of survival-potential and proliferation-potential. We apply these models to a recently studied experimental system. Our results suggest that mechanisms based on fundamental laws of biology can reversibly push an actively-proliferating, and drug-sensitive, cell population to transition into a weakly-proliferative and drug-tolerant state, which will eventually facilitate the emergence of more potent, proliferating and drug-tolerant cells.