Jafarnejad2019 - Mechanistically detailed systems biology modeling of the HGF/Met pathway in hepatocellular carcinoma
Model Identifier
MODEL2003200001
Short description
Hepatocyte growth factor (HGF) signaling through its receptor Met has been implicated in hepatocellular carcinoma tumorigenesis and progression. Met interaction with integrins is shown to modulate the downstream signaling to Akt and ERK (extracellular-regulated kinase). In this study, we developed a mechanistically detailed systems biology model of HGF/Met signaling pathway that incorporated specific interactions with integrins to investigate the efficacy of integrin-binding peptide, AXT050, as monotherapy and in combination with other therapeutics targeting this pathway. Here we report that the modeled dynamics of the response to AXT050 revealed that receptor trafficking is sufficient to explain the effect of Met-integrin interactions on HGF signaling. Furthermore, the model predicted patient-specific synergy and antagonism of efficacy and potency for combination of AXT050 with sorafenib, cabozantinib, and rilotumumab. Overall, the model provides a valuable framework for studying the efficacy of drugs targeting receptor tyrosine kinase interaction with integrins, and identification of synergistic drug combinations for the patients. Model is encoded by Johannes and submitted to BioModels by Ahmad Zyoud.
Format
SBML
(L2V4)
Related Publication
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Mechanistically detailed systems biology modeling of the HGF/Met pathway in hepatocellular carcinoma.
- Jafarnejad M, Sové RJ, Danilova L, Mirando AC, Zhang Y, Yarchoan M, Tran PT, Pandey NB, Fertig EJ, Popel AS
- NPJ systems biology and applications , 1/ 2019 , Volume 5 , pages: 29 , PubMed ID: 31452933
- 1Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD USA.
- Hepatocyte growth factor (HGF) signaling through its receptor Met has been implicated in hepatocellular carcinoma tumorigenesis and progression. Met interaction with integrins is shown to modulate the downstream signaling to Akt and ERK (extracellular-regulated kinase). In this study, we developed a mechanistically detailed systems biology model of HGF/Met signaling pathway that incorporated specific interactions with integrins to investigate the efficacy of integrin-binding peptide, AXT050, as monotherapy and in combination with other therapeutics targeting this pathway. Here we report that the modeled dynamics of the response to AXT050 revealed that receptor trafficking is sufficient to explain the effect of Met-integrin interactions on HGF signaling. Furthermore, the model predicted patient-specific synergy and antagonism of efficacy and potency for combination of AXT050 with sorafenib, cabozantinib, and rilotumumab. Overall, the model provides a valuable framework for studying the efficacy of drugs targeting receptor tyrosine kinase interaction with integrins, and identification of synergistic drug combinations for the patients.
Contributors
Submitter of the first revision: Ahmad Zyoud
Submitter of this revision: Ahmad Zyoud
Modellers: Ahmad Zyoud
Submitter of this revision: Ahmad Zyoud
Modellers: Ahmad Zyoud
Metadata information
isDescribedBy (1 statement)
hasTaxon (1 statement)
hasProperty (3 statements)
occursIn (1 statement)
hasTaxon (1 statement)
hasProperty (3 statements)
Mathematical Modelling Ontology
Ordinary differential equation model
NCIt Hepatocellular Carcinoma
NCIt Hepatocyte Growth Factor
NCIt Hepatocellular Carcinoma
NCIt Hepatocyte Growth Factor
occursIn (1 statement)
Curation status
Non-curated
Modelling approach(es)
Tags
Connected external resources
SBGN view in Newt Editor
| Name | Description | Size | Actions |
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Model files |
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| Jafarnejad2019.2.xml | SBML L2V4 Jafarnejad2019 - Mechanistically detailed systems biology modeling of the HGF/Met pathway in hepatocellular carcinoma_Original | 219.45 KB | Preview | Download |
Additional files |
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| Jafarnejad2019.2.cps | COPASI version 4.27 (Build 217) Jafarnejad2019 - Mechanistically detailed systems biology modeling of the HGF/Met pathway in hepatocellular carcinoma_Original | 397.23 KB | Preview | Download |
- Model originally submitted by : Ahmad Zyoud
- Submitted: Mar 20, 2020 5:47:14 AM
- Last Modified: Mar 20, 2020 5:47:14 AM
Revisions
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Version: 1
- Submitted on: Mar 20, 2020 5:47:14 AM
- Submitted by: Ahmad Zyoud
- With comment: Import of Jafarnejad2019 - Mechanistically detailed systems biology modeling of the HGF/Met pathway in hepatocellular carcinoma