title: Vascular normalization as a therapeutic strategy for malignant and nonmalignant disease.
abstract: Pathological angiogenesis-driven by an imbalance of pro- and antiangiogenic signaling-is a hallmark of many diseases, both malignant and benign. Unlike in the healthy adult in which angiogenesis is tightly regulated, such diseases are characterized by uncontrolled new vessel formation, resulting in a microvascular network characterized by vessel immaturity, with profound structural and functional abnormalities. The consequence of these abnormalities is further modification of the microenvironment, often serving to fuel disease progression and attenuate response to conventional therapies. In this article, we present the "vascular normalization" hypothesis, which states that antiangiogenic therapy, by restoring the balance between pro- and antiangiogenic signaling, can induce a more structurally and functionally normal vasculature in a variety of diseases. We present the preclinical and clinical evidence supporting this concept and discuss how it has contributed to successful treatment of both solid tumors and several benign conditions.
authors.affiliation: Edwin Steele Laboratory for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. jain@steele.mgh.harvard.edu
authors.forename: Shom
authors.initials: S
authors.lastname: Goel
authors.forename: Andus Hon-Kit
authors.initials: AH
authors.lastname: Wong
authors.forename: Rakesh K
authors.initials: RK
authors.lastname: Jain
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D042702:Angiopoietin-2 / Q000502:physiology; D003603:Cytotoxins / Q000008:administration & dosage; D018450:Disease Progression; D006801:Humans; D008268:Macular Degeneration / Q000188:drug therapy; D055806:Microvessels / Q000502:physiology; D009369:Neoplasms / Q000503:physiopathology* / Q000628:therapy*; D018919:Neovascularization, Physiologic; D009464:Neuroma, Acoustic / Q000188:drug therapy; D058226:Plaque, Atherosclerotic / Q000188:drug therapy; D011565:Psoriasis / Q000188:drug therapy; D013683:Telangiectasia, Hereditary Hemorrhagic / Q000188:drug therapy; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000502:physiology
chemical_list: D020533:Angiogenesis Inhibitors; D042702:Angiopoietin-2; D003603:Cytotoxins; D042461:Vascular Endothelial Growth Factor A