  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.
