title: Computational model of EGFR and IGF1R pathways in lung cancer: a Systems Biology approach for Translational Oncology.
abstract: In this paper we propose a Systems Biology approach to understand the molecular biology of the Epidermal Growth Factor Receptor (EGFR, also known as ErbB1/HER1) and type 1 Insulin-like Growth Factor (IGF1R) pathways in non-small cell lung cancer (NSCLC). This approach, combined with Translational Oncology methodologies, is used to address the experimental evidence of a close relationship among EGFR and IGF1R protein expression, by immunohistochemistry (IHC) and gene amplification, by in situ hybridization (FISH) and the corresponding ability to develop a more aggressive behavior. We develop a detailed in silico model, based on ordinary differential equations, of the pathways and study the dynamic implications of receptor alterations on the time behavior of the MAPK cascade down to ERK, which in turn governs proliferation and cell migration. In addition, an extensive sensitivity analysis of the proposed model is carried out and a simplified model is proposed which allows us to infer a similar relationship among EGFR and IGF1R activities and disease outcome.
authors.affiliation: Department of Electronic and Information Engineering, Perugia University, Italy. fortunato.bianconi@diei.unipg.it
authors.forename: Fortunato
authors.initials: F
authors.lastname: Bianconi
authors.forename: Elisa
authors.initials: E
authors.lastname: Baldelli
authors.forename: Vienna
authors.initials: V
authors.lastname: Ludovini
authors.forename: Lucio
authors.initials: L
authors.lastname: Crinò
authors.forename: Antonella
authors.initials: A
authors.lastname: Flacco
authors.forename: Paolo
authors.initials: P
authors.lastname: Valigi
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism*; D003198:Computer Simulation; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D015398:Signal Transduction; D049490:Systems Biology / Q000379:methods*; D057170:Translational Research, Biomedical / Q000379:methods
chemical_list: D007334:Insulin-Like Growth Factor I; D066246:ErbB Receptors