Dataset Information

Jafarnejad2019 - Mechanistically detailed systems biology modeling of the HGF/Met pathway in hepatocellular carcinoma

ABSTRACT: 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.

SUBMITTER: Ahmad Zyoud

PROVIDER: MODEL2003200001 | BioModels | 2020-03-20

REPOSITORIES: BioModels

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			Action	DRS
	MODEL2003200001?filename=Jafarnejad2019.2.cps	Other
	MODEL2003200001?filename=Jafarnejad2019.2.xml	Xml

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Mechanistically detailed systems biology modeling of the HGF/Met pathway in hepatocellular carcinoma.

Jafarnejad Mohammad M Sové Richard J RJ Danilova Ludmila L Mirando Adam C AC Zhang Yu Y Yarchoan Mark M Tran Phuoc T PT Pandey Niranjan B NB Fertig Elana J EJ Popel Aleksander S AS

NPJ systems biology and applications 20190816

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 ...[more]

PMID: 31452933

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