Antiangiogenic therapy: creating a unique "window" of opportunity.
Antiangiogenic therapy for solid tumors clearly destroys tumor vasculature and reduces tumor growth. As an unexpected bonus, drugs that neutralize VEGF signaling generate a "normalization window" for tumor vasculature. This occurs via the recruitment of pericytes to the tumor vasculature, an effect associated with the transient stabilization of vessels and improved oxygen delivery to hypoxic zones. The normalization process is mediated by angiopoietin-1 and matrix metalloproteinases and creates a window of opportunity for improved sensitivity to ionizing radiation and the delivery of chemotherapeutic drugs.
Lin
Michelle I
MI
Yale University School of Medicine, Vascular Cell Signaling and Therapeutics Program, Boyer Center for Molecular Medicine, 295 Congress Avenue, New Haven, CT 06536, USA.
Sessa
William C
WC
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D042683:Angiopoietin-1 / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001485:Basement Membrane / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D001808:Blood Vessels / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D002465:Cell Movement / Q000187:drug effects / Q000528:radiation effects; D017364:Collagenases / Q000378:metabolism; D003131:Combined Modality Therapy / Q000379:methods; D005720:Gamma Rays / Q000627:therapeutic use; D005910:Glioma / Q000188:drug therapy / Q000378:metabolism / Q000532:radiotherapy; D006801:Humans; D051379:Mice; D008954:Models, Biological; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000532:radiotherapy; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000378:metabolism / Q000532:radiotherapy; D020286:Pericytes / Q000187:drug effects / Q000528:radiation effects; D042787:Receptor, TIE-2 / Q000037:antagonists & inhibitors; D013997:Time Factors; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors* / Q000276:immunology; D023041:Xenograft Model Antitumor Assays
D020533:Angiogenesis Inhibitors; D042683:Angiopoietin-1; D000911:Antibodies, Monoclonal; D042787:Receptor, TIE-2; D040301:Vascular Endothelial Growth Factor Receptor-2; D017364:Collagenases