"Antimyeloangiogenic" therapy for cancer by inhibiting PlGF.
Inhibition of tumor angiogenesis emerged as valuable strategy to treat cancer and has revolutionized the face of clinical oncology by prolonging the life of numerous cancer patients. However, the duration of this response is rather short and tumors rapidly evade treatment, leaving antiangiogenic treatment thus far unable to cure cancer. Hence, novel targets are needed to diversify antiangiogenic treatments and to overcome resistance. Recent data support the concept that tumor infiltration by bone marrow-derived myeloid cells confers resistance to current antiangiogenic drugs targeting primarily vascular endothelial growth factor (VEGF). In this review, we will summarize (pre)clinical data on the role of PlGF and its receptor VEGFR-1 in promoting angiogenesis and inflammation, and the "antimyeloangiogenic" activity of an antibody against PlGF (alphaPlGF), which may help to overcome resistance against VEGF(R)Is. Because of these promising results, a humanized alphaPlGF antibody (TB403) is currently evaluated in different phase I clinical trials in cancer patients.
Loges
Sonja
S
Vesalius Research Center (VRC), VIB, Katholieke Universiteit Leuven, Leuven, Belgium.
Schmidt
Thomas
T
Carmeliet
Peter
P
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology*; D006801:Humans; D008954:Models, Biological; D022423:Myeloid Cells / Q000187:drug effects* / Q000378:metabolism; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D000906:Antibodies; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D042461:Vascular Endothelial Growth Factor A; D000072483:Placenta Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1