Kamran Kaveh

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  Short Talk: Evolutionary Dynamics of Tumour Heterogeneity and Plasticity
  Kamran Kaveh

  Ubiquitous proliferation scheme of stem cells let them not only to replenish their own population but also nourish the population of non-stem tumour cells in a hierarchal form and create strong epigenetic heterogeneity in tumours. Cancer stem cells are believed to have strong plastic phenotypic property tuned by microenvironment which can affect their selection dynamics. We construct a general Moran type model to include differentiation and plasticity for cancer stem cell selection. We present analytical and simulation results for fixation probability and time to fixation in such a model. We apply our model to niche succession and clonal conversion in colorectal cancer both in the presence and absence of primary plasticity between stem cells in the niche and their early progenitors. We also address the effect of microenvironment by introducing a spatial model which incorporates variations in fitness parameters as well as geometry of the the organ. Our finding shows that the fixation probability is a strong function of plasticity rate and differentiation probabilities inside stem cell niche. We compare our findings with observations of Vermeulen et al (Science 2013) on stem cell dynamics of intestinal tumour initiation.