title: Multi-level model for the investigation of oncoantigen-driven vaccination effect.
abstract: BACKGROUND
  Cancer stem cell theory suggests that cancers are derived by a population of cells named Cancer Stem Cells (CSCs) that are involved in the growth and in the progression of tumors, and lead to a hierarchical structure characterized by differentiated cell population. This cell heterogeneity affects the choice of cancer therapies, since many current cancer treatments have limited or no impact at all on CSC population, while they reveal a positive effect on the differentiated cell populations.
  
  
  RESULTS
  In this paper we investigated the effect of vaccination on a cancer hierarchical structure through a multi-level model representing both population and molecular aspects. The population level is modeled by a system of Ordinary Differential Equations (ODEs) describing the cancer population's dynamics. The molecular level is modeled using the Petri Net (PN) formalism to detail part of the proliferation pathway. Moreover, we propose a new methodology which exploits the temporal behavior derived from the molecular level to parameterize the ODE system modeling populations. Using this multi-level model we studied the ErbB2-driven vaccination effect in breast cancer.
  
  
  CONCLUSIONS
  We propose a multi-level model that describes the inter-dependencies between population and genetic levels, and that can be efficiently used to estimate the efficacy of drug and vaccine therapies in cancer models, given the availability of molecular data on the cancer driving force.
authors.affiliation: Computer Science Department, University of Turin, Corso Svizzera 185, Torino, Italy. fcordero@di.unito.it
authors.forename: Francesca
authors.initials: F
authors.lastname: Cordero
authors.forename: Marco
authors.initials: M
authors.lastname: Beccuti
authors.forename: Chiara
authors.initials: C
authors.lastname: Fornari
authors.forename: Stefania
authors.initials: S
authors.lastname: Lanzardo
authors.forename: Laura
authors.initials: L
authors.lastname: Conti
authors.forename: Federica
authors.initials: F
authors.lastname: Cavallo
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Balbo
authors.forename: Raffaele
authors.initials: R
authors.lastname: Calogero
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D006801:Humans; D051379:Mice; D008954:Models, Biological; D009369:Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology* / Q000628:therapy*; D014411:Neoplastic Stem Cells / Q000473:pathology; D018719:Erb-b2 Receptor Tyrosine Kinases
chemical_list: D019496:Cancer Vaccines; D018719:Erb-b2 Receptor Tyrosine Kinases