title: New vascular disrupting agents in upper gastrointestinal malignancies.
abstract: Antivascular approaches aim to cause rapid and catastrophic shutdown in the vascular function of the tumour, leading to extensive tumour cell death. Tumour vascular disrupting agents (VDAs) are a new class of cancer therapies that target the existing vasculature of tumours, taking advantage of the relative instability of tumour vasculature and its supporting structures. Treatment with VDAs induces a rapid collapse and regression of tumour vessels, with a consequent deprivation of blood and oxygen which leads to ischemic or hemorrhagic necrosis of the tumour. In this review, an overview of the most recently developed vascular disrupting agents is reported, focusing on the biological effects exerted by these compounds on endothelial cells and tumour vasculature, potentially effective in the treatment of several malignancies including upper gastrointestinal tumours. In particular, we have focused on the antimitotic agent combretastatin and its numerous synthetic analogues such as combretastatin A-4-phosphate, OXI4503, and AVE8062, and on the colchicine analogue ZD6126.
authors.forename: A E
authors.initials: AE
authors.lastname: Quatrale
authors.forename: L
authors.initials: L
authors.lastname: Porcelli
authors.forename: A
authors.initials: A
authors.lastname: Gnoni
authors.forename: G
authors.initials: G
authors.lastname: Numico
authors.forename: A
authors.initials: A
authors.lastname: Paradiso
authors.affiliation: Clinical and Preclinical Pharmacology Laboratory, National Cancer Research Centre - Istituto Tumori Giovanni Paolo II Viale O. Flacco, 65 70125 Bari, Italy. a.azzariti@oncologico.bari.it.
authors.forename: A
authors.initials: A
authors.lastname: Azzariti
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001632:Bibenzyls / Q000627:therapeutic use*; D011756:Diphosphates / Q000627:therapeutic use; D005770:Gastrointestinal Neoplasms / Q000098:blood supply* / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000473:pathology; D009943:Organophosphorus Compounds / Q000627:therapeutic use; D012694:Serine / Q000031:analogs & derivatives / Q000627:therapeutic use; D013267:Stilbenes / Q000627:therapeutic use; D041742:Upper Gastrointestinal Tract / Q000098:blood supply* / Q000187:drug effects / Q000473:pathology*
chemical_list: D020533:Angiogenesis Inhibitors; D001632:Bibenzyls; D011756:Diphosphates; C455219:N-acetylcochinol-O-phosphate; D009943:Organophosphorus Compounds; C465018:Oxi 4503; D013267:Stilbenes; D012694:Serine; C040105:combretastatin; C400245:AC 7700