ArticleNPJ systems biology and applications2019
Mechanistically detailed systems biology modeling of the HGF/Met pathway in hepatocellular carcinoma.
Article in NPJ systems biology and applications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 29 citations in OpenAlex.
- Systems Biology of the Cancer Cell.Annual review of biomedical engineering · 2025Review
- Combining mechanistic quantitative systems pharmacology modeling and patient-derived organoid testing in MET-aberrant non-small cell lung cancer for high-throughput combination efficacy analysis and personalized treatment design.Frontiers in pharmacology · 2025Article
- The MET Oncogene Network of Interacting Cell Surface Proteins.International journal of molecular sciences · 2024Review
- Combining Multikinase Tyrosine Kinase Inhibitors Targeting the Vascular Endothelial Growth Factor and Cluster of Differentiation 47 Signaling Pathways Is Predicted to Increase the Efficacy of Antiangiogenic Combination Therapies.ACS pharmacology & translational science · 2023Article
- Core cysteine residues in the Plasminogen-Apple-Nematode (PAN) domain are critical for HGF/c-MET signaling.Communications biology · 2022Article
- Systems biology of angiogenesis signaling: Computational models and omics.WIREs mechanisms of disease · 2022Review
- Deciphering signal transduction networks in the liver by mechanistic mathematical modelling.The Biochemical journal · 2022Article
- Tumor Microenvironment of Hepatocellular Carcinoma: Challenges and Opportunities for New Treatment Options.International journal of molecular sciences · 2022Review
- A text-based computational framework for patient -specific modeling for classification of cancers.iScience · 2022Article
- c-Met-integrin cooperation: Mechanisms, tumorigenic effects, and therapeutic relevance.Frontiers in cell and developmental biology · 2022Review
- A systems biology model of junctional localization and downstream signaling of the Ang-Tie signaling pathway.NPJ systems biology and applications · 2021Article
- Generation of osimertinib-resistant cells from epidermal growth factor receptor L858R/T790M mutant non-small cell lung carcinoma cell line.Journal of the Chinese Medical Association : JCMA · 2021Article
- Article
- Charting the Fragmented Landscape of Drug Synergy.Trends in pharmacological sciences · 2020Review
- Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.