Cancer spatial evolution in a changing microenvironment
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Abstract
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.
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2017. Cancer spatial evolution in a changing microenvironment. PeerJ Preprints 5:e3052v1 https://doi.org/10.7287/peerj.preprints.3052v1Author comment
Poster presentation for the Evolutionary systems biology of cells symposium of SMBE 2017.
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Competing Interests
The authors declare that they have no competing interests.
Author Contributions
Xiaowei Jiang conceived and designed the experiments, performed the experiments, analyzed the data, contributed reagents/materials/analysis tools, wrote the paper, prepared figures and/or tables, reviewed drafts of the paper.
Ian PM Tomlinson reviewed drafts of the paper, was awarded the advanced ERC grant (EVOCAN-340560).
Data Deposition
The following information was supplied regarding data availability:
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Funding
This work is funded by an ERC advanced grant (EVOCAN-340560). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.