Genetic dissection of tumor angiogenesis: are PlGF and VEGFR-1 novel anti-cancer targets?
Many proliferative diseases, most typically cancer, are driven by uncontrolled blood vessel growth. Genetic studies have been very helpful in unraveling the cellular and molecular players in pathological blood vessel formation and have provided opportunities to reduce tumor growth and metastasis. The fact that tumor vessels and normal blood vessels have distinct properties may help in designing more specific--and therefore safer--anti-angiogenic strategies. Such strategies may interfere with angiogenesis at the cellular or molecular level. Possible molecular targets include angiogenic growth factors and their receptors, proteinases, coagulation factors, junctional/adhesion molecules and extracellular matrix (ECM) components. Some anti-angiogenic drugs, i.e., vascular endothelial growth factor (VEGF) antibodies and VEGF receptor-2 (VEGFR-2) inhibitors, have progressed into clinical cancer trials. While the results of these trials support the potential of anti-angiogenic therapy to treat cancer, they also demonstrate the need for more effective and safer alternatives. Targeting placental growth factor (PlGF) or VEGFR-1 may constitute such an alternative since animal studies have proven their pleiotropic working mechanism and attractive safety profile. Together, these insights may bring anti-angiogenic drugs closer from bench to bedside.
The Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, KULeuven, Campus Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium.
Aernout
A
Luttun
Monica
M
Autiero
Marc
M
Tjwa
Peter
P
Carmeliet
D043925:Angiogenesis Inducing Agents / Q000378:metabolism; D000818:Animals; D001779:Blood Coagulation Factors / Q000378:metabolism; D016503:Drug Delivery Systems; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D042601:Lymphatic Vessels / Q000378:metabolism*; D009369:Neoplasms / Q000098:blood supply*; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000737:chemistry / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*
D043925:Angiogenesis Inducing Agents; D001779:Blood Coagulation Factors; D016326:Extracellular Matrix Proteins; D006133:Growth Substances; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1