Presented by Rob Noble, visiting from ETH Zurich

Abstract

Improvements in cancer prevention, prognosis and treatment can come from understanding how spatial structure shapes evolutionary dynamics. The first part of my talk will concern adaptive therapy, which aims to control tumour burden by maintaining therapy-sensitive cells to exploit their competition with resistant cells. I will present new empirical and mathematical modelling results that illuminate how tumour spatial structure amplifies the fitness penalty of resistant cells, whose relative fitness is a critical determinant of the predicted clinical benefit of adaptive therapy. In the second part, I will take a more general look at how spatial structure determines the mode of tumour evolution. Progressing from the Eden growth model to spatial versions of the Moran process, I will characterize how tissue architecture (cell-cell competition and cell migration) influences the potential for subclonal population growth, the prevalence of clonal sweeps, and the resulting pattern of intratumour heterogeneity. These insights help explain the multiformity of tumour evolution and contribute to establishing a theoretical foundation for predictive oncology.