Bianconi2012 - EGFR and IGF1R pathway in lung cancer

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Short description
Bianconi2012 - EGFR and IGF1R pathway in lung cancer

EGFR and IGF1R pathways play a key role in various human cancers and are crucial for tumour transformation and survival of malignant cells. High EGFR and IGF1R expression and activity has been associated with multiple aspects of cancer progression including tumourigenesis, metastasis, resistance to chemotherapeutics and other molecularly targeted drugs. Here, the biological relationship between the proteins involved in EGFR and IGF1R pathways and the downstream MAPK and PIK3 networks has been modelled to study the time behaviour of the overall system, and the functional interdependencies among the receptors, the proteins and kinases involved.

This model is described in the article:

Bianconi F, Baldelli E, Ludovini V, Crinò L, Flacco A, Valigi P.
Biotechnol Adv. 2012 Jan-Feb;30(1):142-53.

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.

To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Format
SBML (L2V4)
Related Publication
  • Computational model of EGFR and IGF1R pathways in lung cancer: a Systems Biology approach for Translational Oncology.
  • Bianconi F, Baldelli E, Ludovini V, Crinò L, Flacco A, Valigi P
  • Biotechnology advances , 0/ 2012 , Volume 30 , pages: 142-153
  • Department of Electronic and Information Engineering, Perugia University, Italy. fortunato.bianconi@diei.unipg.it
  • 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.
Contributors
Fortunato Bianconi

Metadata information

is
BioModels Database MODEL1209230000
BioModels Database BIOMD0000000427
isDescribedBy
PubMed 21620944
hasTaxon
Taxonomy Homo sapiens
hasProperty
Mathematical Modelling Ontology Ordinary differential equation model
hasVersion
Human Disease Ontology non-small cell lung carcinoma
Curation status
Curated
Original model(s)
http://sourceforge.net/projects/bianconi2012egf/
Name Description Size Actions

Model files

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  • Model originally submitted by : Fortunato Bianconi
  • Submitted: Sep 23, 2012 11:34:38 AM
  • Last Modified: May 23, 2017 11:30:00 AM
Revisions
  • Version: 2 public model Download this version
    • Submitted on: May 23, 2017 11:30:00 AM
    • Submitted by: Fortunato Bianconi
    • With comment: Current version of Bianconi2012 - EGFR and IGF1R pathway in lung cancer
  • Version: 1 public model Download this version
    • Submitted on: Sep 23, 2012 11:34:38 AM
    • Submitted by: Fortunato Bianconi
    • With comment: Original import of EGFR_IGF1R
Curator's comment:
(added: 19 Nov 2012, 13:24:06, updated: 19 Nov 2012, 13:24:06)
The model reproduce figure 2a of the reference publication, by setting EGFR_active = 8000 and IGFR_active = 650. The initial concentrations for reproducing figure 2b and 2c can be obtained from the matlab file of model, which accompanies the reference publication. The model was simulated using Copasi v4.8 (Build 35). The plot was generated using Gnuplot.