title: Cell death and life in cancer: mathematical modeling of cell fate decisions.
abstract: 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.
authors.affiliation: U900 INSERM/Institut Curie/Ecole de Mines, Institut Curie, 26 rue d'Ulm, Paris 75005, France. andrei.zinovyev@curie.fr
authors.forename: Andrei
authors.initials: A
authors.lastname: Zinovyev
authors.forename: Simon
authors.initials: S
authors.lastname: Fourquet
authors.forename: Laurent
authors.initials: L
authors.lastname: Tournier
authors.forename: Laurence
authors.initials: L
authors.lastname: Calzone
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Barillot
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D003198:Computer Simulation; D053263:Gene Regulatory Networks / Q000235:genetics / Q000502:physiology; D006801:Humans; D008954:Models, Biological; D009154:Mutation; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009336:Necrosis; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*
chemical_list: D051017:Apoptosis Regulatory Proteins; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate