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Bianconi2012 - EGFR and IGF1R pathway in lung cancer


ABSTRACT: 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: 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. 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. This model is hosted on BioModels Database and identified by: MODEL1209230000 . To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models . 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.

DISEASE(S): Non-small Cell Lung Carcinoma

SUBMITTER: Fortunato Bianconi  

PROVIDER: BIOMD0000000427 | BioModels | 2012-11-20

REPOSITORIES: BioModels

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Computational model of EGFR and IGF1R pathways in lung cancer: a Systems Biology approach for Translational Oncology.

Bianconi Fortunato F   Baldelli Elisa E   Ludovini Vienna V   Crinò Lucio L   Flacco Antonella A   Valigi Paolo P  

Biotechnology advances 20110518 1


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 hyb  ...[more]

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