title: A cellular automaton model for tumor dormancy: emergence of a proliferative switch.
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.
authors.affiliation: Department of Chemistry, Princeton University, Princeton, New Jersey, United States of America; Physical Science in Oncology Center, Princeton University, Princeton, New Jersey, United States of America.
authors.forename: Duyu
authors.initials: D
authors.lastname: Chen
authors.affiliation: Physical Science in Oncology Center, Princeton University, Princeton, New Jersey, United States of America; Materials Science and Engineering, Arizona State University, Tempe, Arizona, United States of America.
authors.forename: Yang
authors.initials: Y
authors.lastname: Jiao
authors.affiliation: Department of Chemistry, Princeton University, Princeton, New Jersey, United States of America; Physical Science in Oncology Center, Princeton University, Princeton, New Jersey, United States of America; Department of Physics, Princeton University, Princeton, New Jersey, United States of America; Program in Applied and Computational Mathematics, Princeton University, Princeton, New Jersey, United States of America; Princeton Institute for the Science and Technology of Materials, Princeton University, Princeton, New Jersey, United States of America.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Torquato
mesh_terms: D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D008954:Models, Biological; D009369:Neoplasms / Q000098:blood supply / Q000276:immunology / Q000473:pathology*; D009389:Neovascularization, Pathologic; D059016:Tumor Microenvironment