title: Targeting the Angiopoietin-2/Tie-2 axis in conjunction with VEGF signal interference.
abstract: Anti-angiogenic therapies target the tumor vasculature, impairing its development and growth. It was hypothesized over 40 years ago by the late Judah Folkman and Julie Denekamp that depriving a tumor of oxygen and nutrients, by targeting the tumor vasculature, could have therapeutic benefits. Identification of growth factors and signaling pathways important in angiogenesis subsequently led to the development of a series of anti-angiogenic agents that over the past decade have become part of the standard of care in several disease settings. Unfortunately not all patients respond to the currently available anti-angiogenic therapies while others become resistant to these agents following prolonged exposure. Identification of new pathways that may drive angiogenesis led to the development of second-generation anti-angiogenic agents such as those targeting the Ang-2/Tie2 axis. Recently, it has become clear that combination of first and second generation agents targeting the blood vessel network can lead to outcomes superior to those using either agent alone. The present review focuses on the current status of VEGF and Ang-2 targeted agents and the potential utility of using them in combination to impair tumor angiogenesis.
authors.affiliation: Department of Pathology, University of Florida College of Medicine, 1395 Center Drive, Gainesville, FL 32610, USA. Electronic address: nmolnar@ufl.edu.
authors.forename: Nikolett M
authors.initials: NM
authors.lastname: Biel
authors.affiliation: Department of Radiation Oncology, University of Florida College of Medicine, 2000 SW, Archer Road, Gainesville, FL 32610, USA.
authors.forename: Dietmar W
authors.initials: DW
authors.lastname: Siemann
mesh_terms: D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D042702:Angiopoietin-2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D055808:Drug Discovery; D019008:Drug Resistance, Neoplasm; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic; D042787:Receptor, TIE-2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D059016:Tumor Microenvironment; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
chemical_list: C586513:ANGPT2 protein, human; D020533:Angiogenesis Inhibitors; D042702:Angiopoietin-2; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042787:Receptor, TIE-2
keywords: Ang-2 targeting; Angiogenesis; Anti-angiogenic therapy; Combination therapy; VEGF targeting