Tumor microvasculature and microenvironment: targets for anti-angiogenesis and normalization.

By Dai Fukumura, Rakesh K. Jain. Microvascular Research, 2007

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Regorafenib (BAY 73‐4506): A new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity (2011, neutral): “The reduced total tumor blood volume may be explained by a decrease in the number of microvessels and by a transient normalization of the tumor blood vessels.(39) This is supported by the observation of a decrease in tumor microvasculature in vivo after 5 days of oral dosing with regorafenib (Figs.”
Vascular Endothelial Growth Factor (VEGF) and Its Receptor (VEGFR) Signaling in Angiogenesis: A Crucial Target for Anti- and Pro-Angiogenic Therapies. (2011, background): “Another hypothesis regarding the efficacy of the anti-VEGF antibody and anti-VEGFR tyrosine kinase inhibitor on tumor growth in patients is termed “vascular normalization,” whereby the absorption of VEGF-A induces a transiently normalized vascular structure, more stabilized and well covered with per”
Gemcitabine plus bevacizumab compared with gemcitabine plus placebo in patients with advanced pancreatic cancer: phase III trial of the Cancer and Leukemia Group B (CALGB 80303). (2010, background): “By normalizing tumor vasculature, VEGF inhibitors may enhance drug delivery, thereby increasing chemotherapy activity.(27) Gemcitabine may be the most active agent for pancreatic cancer, but it is only modestly effective.”