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A Cellular Automaton Model for Tumor Dormancy: Emergence of a Proliferative Switch

Author(s): Chen, Duyu; Jiao, Yang; Torquato, Salvatore

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Abstract: Malignant cancers that lead to fatal outcomes for patients may remain dormant for very long periods of time. Although individual mechanisms such as cellular dormancy, angiogenic dormancy and immunosurveillance have been proposed, a comprehensive understanding of cancer dormancy and the ‘‘switch’’ from a dormant to a proliferative state still needs to be strengthened from both a basic and clinical point of view. Computational modeling enables one to explore a variety of scenarios for possible but realistic microscopic dormancy mechanisms and their predicted outcomes. The aim of this paper is to devise such a predictive computational model of dormancy with an emergent ‘‘switch’’ behavior. Specifically, we generalize a previous cellular automaton (CA) model for proliferative growth of solid tumor that now incorporates a variety of cell-level tumor-host interactions and different mechanisms for tumor dormancy, for example the effects of the immune system. Our new CA rules induce a natural ‘‘competition’’ between the tumor and tumor suppression factors in the microenvironment. This competition either results in a ‘‘stalemate’’ for a period of time in which the tumor either eventually wins (spontaneously emerges) or is eradicated; or it leads to a situation in which the tumor is eradicated before such a ‘‘stalemate’’ could ever develop. We also predict that if the number of actively dividing cells within the proliferative rim of the tumor reaches a critical, yet low level, the dormant tumor has a high probability to resume rapid growth. Our findings may shed light on the fundamental understanding of cancer dormancy.
Publication Date: 16-Oct-2014
Electronic Publication Date: 16-Oct-2014
Citation: Chen, Duyu, Jiao, Yang, Torquato, Salvatore. (2014). A Cellular Automaton Model for Tumor Dormancy: Emergence of a Proliferative Switch. PLoS ONE, 9 (10), e109934 - e109934. doi:10.1371/journal.pone.0109934
DOI: doi:10.1371/journal.pone.0109934
EISSN: 1932-6203
Pages: 9:10, e109934-1 - e109934-10
Type of Material: Journal Article
Journal/Proceeding Title: PLoS ONE
Version: Final published version. This is an open access article.



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