Cell Death and Life in Cancer: Mathematical Modeling of Cell Fate Decisions
Tumor development is characterized by a compromised balance between cell life and death decision mechanisms, which are tightly regulated in normal cells. Understanding this process provides insights for developing new treatments for fighting with cancer. We present a study of a mathematical model describing cellular choice between survival and two alternative cell death modalities: apoptosis and necrosis. The model is implemented in discrete modeling formalism and allows to predict probabilities of having a particular cellular phenotype in response to engagement of cell death receptors. Using an original parameter sensitivity analysis developed for discrete dynamic systems, we determine variables that appear to be critical in the cellular fate decision and discuss how they are exploited by existing cancer therapies.
KeywordsFragile Site Cellular Phenotype Logical Rule Priority Class Cell Fate Decision
We would like to acknowledge support by the APO-SYS EU FP7 project. A. Zinovyev, S. Fourquet, L. Calzone and E. Barillot are members of the team “Systems Biology of Cancer”, Equipe labellisee par la Ligue Nationale Contre le Cancer. L. Tournier is member of the Systems Biology team in the laboratory MIG of INRA (French Institute for Agronomical Research). The study was also funded by the Projet Incitatif Collaboratif “Bioinformatics and Biostatistics of Cancer” at Institut Curie.
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