biostudies-literatureZhang XYNCI NIH HHSNIGMS NIH HHSe92https://www.ebi.ac.uk/biostudies/studies/S-EPMC3910016biostudies-literatureUnknown3A 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 aCPT: pharmacometrics & systems pharmacologyA General Network Pharmacodynamic Model-Based Design Pipeline for Customized Cancer Therapy Applied to the VEGFR Pathway.PMC3910016P50 GM071558R01 CA127963R01 CA072937Zhang XYBirtwistle MRGallo JMfalseA General Network Pharmacodynamic Model-Based Design Pipeline for Customized Cancer Therapy Applied to the VEGFR Pathway.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 a2014-01-01T00:00:00Z2014 Jan2025-05-18T11:15:59.009Z2025-05-18T11:15:59.009ZS-EPMC39100162442959310.1038/psp.2013.65