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

摘要: Elevated interstitial fluid pressure, a hallmark of solid tumors, can compromise the delivery therapeutics to tumors. Here we show that blocking vascular endothelial growth factor (VEGF) signaling by DC101 (a VEGF-receptor-2 antibody) decreases not restoring lymphatic function, but producing morphologically and functionally "normalized" network. We demonstrate normalization process prunes immature vessels improves integrity function remaining vasculature enhancing perivascular cell basement membrane coverage. also induces hydrostatic pressure gradient across wall, which leads deeper penetration molecules into Thus, may contribute improved survival rates in tumor-bearing animals colorectal carcinoma patients treated with an anti-VEGF antibody combination cytotoxic therapies.