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Pro‐angiogenic and anti‐angiogenic therapies targeting the VEGF‐VEGFR system
Author(s) -
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.592.27
Subject(s) - medicine , vegf receptors , macular degeneration , receptor , cancer research , therapeutic approach , vascular endothelial growth factor , vascular endothelial growth factor a , bioinformatics , biology , disease , ophthalmology
The vascular endothelial growth factors (VEGFs) have become important therapeutic targets in multiple diseases. VEGF antagonists have been approved for use in several cancers and age‐related macular degeneration, to reduce ectopic microvasculature. Gene and protein delivery of VEGF and VEGF agonists have been proposed as therapeutic strategies to increase microcirculatory flow and oxygen delivery for diseases of hypovascularization (notably coronary and peripheral arterial diseases), with mixed results so far. We have developed computational models of VEGF and its receptors, and used them to predict optimal therapeutic targets. Surprisingly, for both pro‐ and anti‐angiogenic therapies, targeting of VEGF receptors ‐ rather than, or in addition to, the ligands ‐ produced better outcomes. In addition, both microenvironment and interpersonal variability significantly impact the efficacy of the therapies in a predictable way, indicating benefits of a combined experimental‐computational approach (personalized medicine). Using these models, we identify therapy‐responsive subgroups and lay out basic principles for therapeutic targeting of a cytokine system. Support provided by: NIH‐R33‐ HL087351 , NIH‐R01‐ HL079653 and NIH‐T32‐HL007284.