title: Targeting angiopoietin-2 signaling in cancer therapy.
abstract: BACKGROUND
  Over the past decade, several anti-angiogenic strategies have been devised to target a wide spectrum of malignancies. The most widely utilized approach involves abrogation of vascular endothelial growth factor receptor signaling through either consumption of ligand (i.e., with the monoclonal antibody bevacizumab) or through direct inhibition of the receptor tyrosine kinase domain (i.e., with small molecules such as sunitinib or sorafenib). While these agents do appear to delay cancer progression in the clinic, they are not curative approaches.
  
  
  METHODS
  A novel anti-angiogenic strategy involves inhibition of signaling along the Ang/Tie-2 axis, a pathway critical for mediating endothelial and perivascular cell interactions. While several agents (i.e., AMG-386 and regorafenib) have reached late stages of clinical development, others (i.e., ARRY614 and CEP-11981) are in their relative infancy. Herein, we will outline the clinical trajectory of wide spectrum Ang/Tie-2 inhibitors, with attention to data evaluating combinations with cytotoxic therapy or other targeted agents.
  
  
  CONCLUSIONS
  Provided that these approaches to not drastically augment toxicity, they may represent the ideal path for further development of this class of agents.
authors.affiliation: City of Hope Comprehensive Cancer Center, Department of Medical Oncology & Experimental Therapeutics, 1500 East Duarte Road, Duarte, CA 91010, USA.
authors.forename: Zeynep
authors.initials: Z
authors.lastname: Eroglu
authors.forename: Cy A
authors.initials: CA
authors.lastname: Stein
authors.forename: Sumanta K
authors.initials: SK
authors.lastname: Pal
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D042702:Angiopoietin-2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods*; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000517:prevention & control*; D011485:Protein Binding; D042787:Receptor, TIE-2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D020533:Angiogenesis Inhibitors; D042702:Angiopoietin-2; D000911:Antibodies, Monoclonal; D011993:Recombinant Fusion Proteins; D042787:Receptor, TIE-2; C551398:trebananib