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• W2806081657 abstract "In this thesis we develop minimal models of the relationship between motility, growth, and evolution of cancer cells. We utilise simple simulations of a population of individual cells in space to examine how changes in mechanical properties of invasive cells and their surroundings can affect the speed of cell migration. We also find that the growth rate of large lesions depends weakly on the migration speed of escaping cells, and has stronger and more complex dependencies on the rates of other stochastic processes in the model, namely the rate at which cells transition to being motile and the reverse rate at which cells cease to be motile. To examine how the rates of growth and evolution of an ensemble of cancerous lesions depends on their geometry and underlying fitness landscape, we develop an analytical framework in which the spatial structure is coarse grained and the cancer treated as a continuously growing system with stochastic migration events. Both approaches conclude that the whole ensemble can undergo migration-driven exponential growth regardless of the dependence of size on time of individual lesions, and that the relationship between growth rate and rate of migration is determined by the geometrical constraints of individual lesions. We also find that linear fitness landscapes result in faster-than-exponential growth of the ensemble, and we can determine the expected number of driver mutations present in several important cases of the model. Finally, we study data from a clinical study of the effectiveness of a new low-dose combined chemotherapy. This enables us to test some important hypotheses about the growth rate of pancreatic cancers and the speed with which evolution occurs in reality. Despite this, we find that the frequency of resistant mutants is far too high to be explained without resorting to novel mechanisms of cross-resistance to multiple drugs." @default.
• W2806081657 created "2018-06-13" @default.
• W2806081657 creator A5001277069 @default.
• W2806081657 date "2018-07-02" @default.
• W2806081657 modified "2023-09-27" @default.
• W2806081657 title "Minimal models of invasion and clonal selection in cancer" @default.
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