title: Angiogenic inhibitors in gastric cancers and gastroesophageal junction carcinomas: A critical insight.
abstract: Advanced gastric cancer ranks second as the global leading cause of cancer-related death and improvements in systemic chemotherapy have reached a plateau. Advanced molecular sequencing techniques help identifying patients more likely to respond to targeted agents; nevertheless we are still far from major breakthroughs. Although antiangiogenic drugs have produced notable advances, redundant pathways or mechanisms of resistance may limit their efficacy. Novel compounds have been recently developed to specifically target VEGF receptors, PlGF, FGF, MET, and angiopoietin. Ramucirumab, a monoclonal antibody specifically directed against the VEGFR-2, has emerged as a novel therapeutic opportunity. REGARD and RAINBOW were the first phase III studies to report the value of this strategy in gastric cancer patients, and other ongoing trials are testing novel antiangiogenic compounds. The aim of our review is to present the state-of-the-art of novel antiangiogenic compounds in advanced gastric cancer, underlying the biology, their mechanism of action, and their clinical results.
authors: Department of Medical Oncology, University and General Hospital, Udine, Italy. Electronic address: aprile.giuseppe@aoud.sanita.fvg.it.
authors: Giuseppe
authors: G
authors: Aprile
authors: Department of Medical Oncology, University and General Hospital, Udine, Italy.
authors: Elena
authors: E
authors: Ongaro
authors: Clinical Pharmacology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Italy.
authors: Marzia
authors: M
authors: Del Re
authors: Department of Medical Oncology, University and General Hospital, Udine, Italy.
authors: Stefania Eufemia
authors: SE
authors: Lutrino
authors: Department of Medical Oncology, University and General Hospital, Udine, Italy.
authors: Marta
authors: M
authors: Bonotto
authors: Department of Medical Oncology, University and General Hospital, Udine, Italy.
authors: Laura
authors: L
authors: Ferrari
authors: Department of Medical Oncology, University and General Hospital, Udine, Italy.
authors: Karim
authors: K
authors: Rihawi
authors: Department of Medical Oncology, University and General Hospital, Udine, Italy.
authors: Giovanni Gerardo
authors: GG
authors: Cardellino
authors: Department of Medical Oncology, University and General Hospital, Udine, Italy.
authors: Nicoletta
authors: N
authors: Pella
authors: Clinical Pharmacology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Italy.
authors: Romano
authors: R
authors: Danesi
authors: Department of Medical Oncology, University and General Hospital, Udine, Italy.
authors: Gianpiero
authors: G
authors: Fasola
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D002277:Carcinoma / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004938:Esophageal Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors / Q000378:metabolism; D013274:Stomach Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000096662:Ramucirumab
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D008565:Membrane Proteins; D019859:Proto-Oncogene Proteins c-met; D040301:Vascular Endothelial Growth Factor Receptor-2; D000096662:Ramucirumab; C098069:PIGF protein, human; C000588866:KDR protein, human; C491743:MET protein, human
keywords: Advanced gastric cancer; Angiogenesis; Bevacizumab; Ramucirumab