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Effects of an anti‐VEGF administration on whole‐body VEGF distribution assessed by a molecularly‐detailed pharmacokinetic model: a cancer study
Author(s) -
Stefanini Marianne O,
Wu Florence TH,
Mac Gabhann Feilim,
Popel Aleksander S
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.592.22
Subject(s) - vegf receptors , vascular endothelial growth factor , angiogenesis , pharmacokinetics , medicine , bevacizumab , cancer , distribution (mathematics) , pharmacology , vascular permeability , cancer research , cytokine , secretion , chemotherapy , mathematical analysis , mathematics
Vascular endothelial growth factor (VEGF), a potent cytokine stimulating angiogenesis, has been reported to be overexpressed in cancer making it a good target for anti‐angiogenic treatment. We constructed a molecularly‐detailed in silico model composed of three compartments (blood plus healthy and diseased tissues). Our model provides insights on the VEGF distribution in each compartment and serves to investigate the possible origins of the plasma VEGF increase observed in cancer patients. We also use this model to predict the effects of anti‐VEGF treatment through different modes of injection (slow infusion, metronomic therapy) on the VEGF profile in each compartment. We find that: 1) an increase of VEGF secretion by the tumor and/or an increase in vascular permeability of VEGF in tumor cannot solely explain the several‐fold plasma VEGF increase observed in cancer patients; 2) the introduction of an anti‐VEGF agent leads to a new pseudo‐steady‐state plasma VEGF level when administered in a metronomic fashion. These findings provide new insights and can be applied to optimizing anti‐angiogenic therapies targeting VEGF.