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Testing clinical therapeutic angiogenesis using basic fibroblast growth factor (FGF‐2)
Author(s) -
Aviles Ronnier J,
Annex Brian H,
Lederman Robert J
Publication year - 2003
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0705493
Subject(s) - therapeutic angiogenesis , angiogenesis , fibroblast growth factor , medicine , neovascularization , clinical trial , basic fibroblast growth factor , extracellular matrix , coronary artery disease , cancer research , growth factor , pharmacology , immunology , oncology , receptor , biology , microbiology and biotechnology
Therapeutic angiogenesis represents an attempt to relieve inadequate blood flow by the directed growth and proliferation of blood vessels. Neovascularization is a complex process involving multiple growth factors, receptors, extracellular matrix glycoproteins, intracellular and extracellular signaling pathways, and local and bone‐marrow‐derived constituent cells, all responding to a symphonic arrangement of temporal and spatial cues. In cardiovascular disease, patients with refractory angina and lower extremity intermittent claudication seem most amenable to early tests of therapeutic angiogenesis. Monotherapy with the recombinant protein basic fibroblast growth factor (FGF‐2) has been tested in six human trials. These have shown provisional safety, and two have provided ‘proof of concept’ for the strategy of therapeutic angiogenesis. One large randomized phase II trial failed to show significant efficacy in coronary artery disease. Another showed significant efficacy in peripheral artery disease, although the magnitude of benefit was disappointing at the dose tested. This overview details the suitable clinical trial design and further steps toward the clinical development of FGF‐2. British Journal of Pharmacology (2003) 140 , 637–646. doi: 10.1038/sj.bjp.0705493

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