title: Dynamic computational model suggests that cellular citizenship is fundamental for selective tumor apoptosis.
abstract: Computational models in the field of cancer research have focused primarily on estimates of biological events based on laboratory generated data. We introduce a novel in-silico technology that takes us to the next level of prediction models and facilitates innovative solutions through the mathematical system. The model's building blocks are cells defined phenotypically as normal or tumor, with biological processes translated into equations describing the life protocols of the cells in a quantitative and stochastic manner. The essentials of communication in a society composed of normal and tumor cells are explored to reveal "protocols" for selective tumor eradication. Results consistently identify "citizenship properties" among cells that are essential for the induction of healing processes in a healthy system invaded by cancer. These properties act via inter-cellular communication protocols that can be optimized to induce tumor eradication along with system recovery. Within the computational systems, the protocols universally succeed in removing a wide variety of tumors defined by proliferation rates, initial volumes, and apoptosis resistant phenotypes; they show high adaptability for biological details and allow incorporation of population heterogeneity. These protocols work as long as at least 32% of cells obey extra-cellular commands and at least 28% of cancer cells report their deaths. This low percentage implies that the protocols are resilient to the suboptimal situations often seen in biological systems. We conclude that our in-silico model is a powerful tool to investigate, to propose, and to exercise logical anti-cancer solutions. Functional results should be confirmed in a biological system and molecular findings should be loaded into the computational model for the next level of directed experiments.
authors.affiliation: Department of Computer Science, University of Massachusetts Amherst, Amherst, Massachusetts, United States of America.
authors.forename: Megan
authors.initials: M
authors.lastname: Olsen
authors.forename: Nava
authors.initials: N
authors.lastname: Siegelmann-Danieli
authors.forename: Hava T
authors.initials: HT
authors.lastname: Siegelmann
mesh_terms: D017209:Apoptosis; D003198:Computer Simulation; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000473:pathology*; D013269:Stochastic Processes