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Cancer associated fibroblasts and alectinib switch the evolutionary games that non-small cell lung cancer plays

Artem Kaznatcheev, Jeffrey Peacock, David Basanta, Andriy Marusyk, Jacob G. Scott
doi: https://doi.org/10.1101/179259
Artem Kaznatcheev
1Department of Computer Science, University of Oxford, Oxford, UK
2Department of Translational Hematology & Oncology Research, Cleveland Clinic, Cleveland, OH, USA
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Jeffrey Peacock
3Department of Radiation Oncology, Moffitt Cancer Center, Tampa, FL, USA
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David Basanta
4Department of Integrated Mathematical Oncology, Moffitt Cancer Center, Tampa, FL, USA
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Andriy Marusyk
5Department of Cancer Imaging and Metabolism, Moffitt Cancer Center, Tampa, FL, USA
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Jacob G. Scott
2Department of Translational Hematology & Oncology Research, Cleveland Clinic, Cleveland, OH, USA
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Abstract

Tumors are heterogeneous, evolving ecosystems [1, 2], composed of sub-populations of neoplastic cells that follow distinct strategies for survival and propagation [3]. The success of a strategy defining any single neoplastic sub-population is dependent on the distribution of other strategies, and on various components of the tumour microenvironment like cancer associated fibroblasts (CAFs) [4]. The rules mapping the population’s strategy distribution to the fitness of individual strategies can be represented as an evolutionary game [5–12]. In four different environments, we measure the games between treatment naive (Alectinib therapy sensitive) cells and a derivative line in which resistance was previously evolved [13]. We find that the games are not only qualitatively different between different environments, but that targeted therapy and the presence of CAFs qualitatively switch the type of game being played. This provides the first empirical confirmation for the theoretical postulate of evolutionary game theory (EGT) in mathematical oncology that we can treat not just the player, but also the game. Although we concentrate on measuring games played by cancer cells, the measurement methodology we develop can be used to advance the study of games in other microscopic systems.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted August 21, 2017.
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Cancer associated fibroblasts and alectinib switch the evolutionary games that non-small cell lung cancer plays
Artem Kaznatcheev, Jeffrey Peacock, David Basanta, Andriy Marusyk, Jacob G. Scott
bioRxiv 179259; doi: https://doi.org/10.1101/179259
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Cancer associated fibroblasts and alectinib switch the evolutionary games that non-small cell lung cancer plays
Artem Kaznatcheev, Jeffrey Peacock, David Basanta, Andriy Marusyk, Jacob G. Scott
bioRxiv 179259; doi: https://doi.org/10.1101/179259

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