Created on 25th June 2017
Cancer development as an ecological and evolutionary process is poorly understood, which includes early cancer evolution, malignancy and metastasis. It was hypothesised that the tumour microenvironment (TME) plays a critical role in this process. Unfortunately, in most cancer modelling studies the TME is ignored or considered static and different cancers are often studied in isolation. There is a lack of a general theory of cancer adaptive evolution (CAE). Here I establish a genetic and phenotypic model of cancer three-dimensional (3D) spatial evolution in a changing TME. With 3D individual-based simulations I show how cancer cells adapt to diverse changing TME conditions and selection intensities. I am able to capture key histological characteristics of various cancer forms including complex dynamics of spatial-temporal heterogeneity of subclonal fitness and subclonal mixing, ball-like and non-ball-like subclonal structures. Moreover, I identify key evolutionary and phylogenetic patterns of CAE under various combinations of phenotypic, genetic, population genetic and changing TME conditions. I show classical drivers, mini drivers, Darwinian and neutral/nearly neutral evolution and cost of complexity. I demonstrate the importance of ecology in CAE. I show that there are fundamental differences in the mode of CAE when the TME is changing, which is the limiting factor of CAE. Finally, I discuss important implications for cancer evolution theories and cancer personalised medicine.Show more
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