ArticleCPT: pharmacometrics & systems pharmacology2014
A General Network Pharmacodynamic Model-Based Design Pipeline for Customized Cancer Therapy Applied to the VEGFR Pathway.
Article in CPT: pharmacometrics & systems pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 34 citations in OpenAlex.
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- Regulation of CSF and Brain Tissue Sodium Levels by the Blood-CSF and Blood-Brain Barriers During Migraine.Frontiers in computational neuroscience · 2020Article
- Applications of Quantitative Systems Pharmacology in Model-Informed Drug Discovery: Perspective on Impact and Opportunities.CPT: pharmacometrics & systems pharmacology · 2019Article
- Mathematical model of hypoxia and tumor signaling interplay reveals the importance of hypoxia and cell-to-cell variability in tumor growth inhibition.BMC bioinformatics · 2019Article
- Translational Quantitative Systems Pharmacology in Drug Development: from Current Landscape to Good Practices.The AAPS journal · 2019Review
- Pharmacodynamic Models of Differential Bortezomib Signaling Across Several Cell Lines of Multiple Myeloma.CPT: pharmacometrics & systems pharmacology · 2019Article
- Multi-Scale Network Model Supported by Proteomics for Analysis of Combined Gemcitabine and Birinapant Effects in Pancreatic Cancer Cells.CPT: pharmacometrics & systems pharmacology · 2018Article
- Multiscale systems pharmacological analysis of everolimus action in hepatocellular carcinoma.Journal of pharmacokinetics and pharmacodynamics · 2018Article
- How to mathematically optimize drug regimens using optimal control.Journal of pharmacokinetics and pharmacodynamics · 2018Article
- Integrating Transcriptomic Data with Mechanistic Systems Pharmacology Models for Virtual Drug Combination Trials.ACS chemical neuroscience · 2018Article
- Computer Simulation of TSP1 Inhibition of VEGF-Akt-eNOS: An Angiogenesis Triple Threat.Frontiers in physiology · 2018Article
- QSP Toolbox: Computational Implementation of Integrated Workflow Components for Deploying Multi-Scale Mechanistic Models.The AAPS journal · 2017Article
- Computational investigation of sphingosine kinase 1 (SphK1) and calcium dependent ERK1/2 activation downstream of VEGFR2 in endothelial cells.PLoS computational biology · 2017Article
- Precision or Personalized Medicine for Cancer Chemotherapy: Is there a Role for Herbal Medicine.Molecules (Basel, Switzerland) · 2016Review
- CNS Anticancer Drug Discovery and Development Conference White Paper.Neuro-oncology · 2015Article
- Molecular mechanism matters: Benefits of mechanistic computational models for drug development.Pharmacological research · 2015Review
- Systems biology of the microvasculature.Integrative biology : quantitative biosciences from nano to macro · 2015Review
- Sobol Sensitivity Analysis: A Tool to Guide the Development and Evaluation of Systems Pharmacology Models.CPT: pharmacometrics & systems pharmacology · 2015Article
- Systems pharmacology approaches for optimization of antiangiogenic therapies: challenges and opportunities.Frontiers in pharmacology · 2015Article
- Quantitative insight in utilizing circulating angiogenic factors as biomarkers for antiangiogenic therapy: systems pharmacology approach.CPT: pharmacometrics & systems pharmacology · 2014Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
A unified approach to optimize multidrug chemotherapy using a pharmacokinetic (PK)/enhanced pharmacodynamic model was developed using the vascular endothelial growth factor receptor (VEGFR) signaling system. The base VEGFR network model, characterized by ligand-receptor interactions, enzyme recruitment (Grb2-Sos, phospholipase C γ (PLCγ), and phosphoinositide-3 kinase (PI3K)), and downstream mitogen-activated protein kinase and Akt cascade activation, was linked to a sunitinib (VEGFR inhibitor) PK model and underwent Sobol sensitivity analysis that revealed potential sunitinib-enhancing mechanisms. Drugs targeting these mechanisms (a VEGF inhibitor, a PI3K inhibitor, a PLCγ inhibitor, and a mitogen-activated protein kinase inhibitor) and sunitinib were input to optimization-based control analyses to design multidrug regimens that maintained 80% pERK and pAkt inhibition for 28 days while minimizing drug dose. The resultant combination regimens contained both continuous and discontinuous schedules, mostly at low doses, and were altered by oncogenic mutations. This pipeline of computational analyses demonstrates how model-based methods can capture the complexities of drug action, tailor cancer chemotherapy, and empower personalized medicine.
Identifiers
What OpenQuestion holds
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 OpenQuestion graph.