title: Predictive mathematical models of cancer signalling pathways.
abstract: Complex intracellular signalling networks integrate extracellular signals and convert them into cellular responses. In cancer cells, the tightly regulated and fine-tuned dynamics of information processing in signalling networks is altered, leading to uncontrolled cell proliferation, survival and migration. Systems biology combines mathematical modelling with comprehensive, quantitative, time-resolved data and is most advanced in addressing dynamic properties of intracellular signalling networks. Here, we introduce different modelling approaches and their application to medical systems biology, focusing on the identifiability of parameters in ordinary differential equation models and their importance in network modelling to predict cellular decisions. Two related examples are given, which include processing of ligand-encoded information and dual feedback regulation in erythropoietin (Epo) receptor signalling. Finally, we review the current understanding of how systems biology could foster the development of new treatment strategies in the context of lung cancer and anaemia.
authors.affiliation: Systems Biology of Signal Transduction, DKFZ-ZMBH Alliance, German Cancer Research Center, Heidelberg, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Bachmann
authors.forename: A
authors.initials: A
authors.lastname: Raue
authors.forename: M
authors.initials: M
authors.lastname: Schilling
authors.forename: V
authors.initials: V
authors.lastname: Becker
authors.forename: J
authors.initials: J
authors.lastname: Timmer
authors.forename: U
authors.initials: U
authors.lastname: Klingmüller
mesh_terms: D000740:Anemia / Q000139:chemically induced / Q000188:drug therapy; D000970:Antineoplastic Agents / Q000009:adverse effects; D002470:Cell Survival / Q000502:physiology; D016207:Cytokines / Q000378:metabolism; D004921:Erythropoietin / Q000009:adverse effects / Q000378:metabolism; D005544:Forecasting; D006801:Humans; D016013:Likelihood Functions; D008175:Lung Neoplasms / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D008433:Mathematics; D008954:Models, Biological; D017467:Receptors, Erythropoietin / Q000037:antagonists & inhibitors / Q000502:physiology*; D011994:Recombinant Proteins; D012307:Risk Factors; D015398:Signal Transduction / Q000502:physiology*; D049490:Systems Biology / Q000379:methods*; D014157:Transcription Factors / Q000502:physiology
chemical_list: D000970:Antineoplastic Agents; D016207:Cytokines; D017467:Receptors, Erythropoietin; D011994:Recombinant Proteins; D014157:Transcription Factors; D004921:Erythropoietin