Vascular Normalization by Vascular Endothelial Growth Factor Receptor 2 Blockade Induces a Pressure Gradient Across the Vasculature and Improves Drug Penetration in Tumors

• Published in: Cancer research (Chicago, Ill.) Vol. 64; no. 11; pp. 3731 - 3736
• Main Authors: Tong, Ricky T., Boucher, Yves, Kozin, Sergey V., Winkler, Frank, Hicklin, Daniel J., Jain, Rakesh K.
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.06.2004
• Subjects: Animals; Antibodies - immunology; Antibodies - pharmacology; Antineoplastic agents; Biological and medical sciences; Capillary Permeability - drug effects; Cell Line, Tumor; Humans; Hydrostatic Pressure; Medical sciences; Mice; Mice, SCID; Neoplasms - blood supply; Neoplasms - drug therapy; Neovascularization, Pathologic - metabolism; Neovascularization, Pathologic - therapy; Pharmacology. Drug treatments; Serum Albumin, Bovine - pharmacokinetics; Tumors; Vascular Endothelial Growth Factor Receptor-2 - antagonists & inhibitors; Vascular Endothelial Growth Factor Receptor-2 - immunology; Drug; Gradient; Penetration; Blood vessel; Circulatory system; Malignant tumor; Vascular endothelial growth factor receptor 2; Pressure

Elevated interstitial fluid pressure, a hallmark of solid tumors, can compromise the delivery of therapeutics to tumors. Here we show that blocking vascular endothelial growth factor (VEGF) signaling by DC101 (a VEGF-receptor-2 antibody) decreases interstitial fluid pressure, not by restoring lympha...