title: Relevance of angiogenesis in neuroendocrine tumors.
abstract: While traditional cytotoxic drugs have shown limited efficacy in neuroendocrine tumors (NETs), their biological features have been characterized and can be exploited therapeutically. Their most prominent trait is an extraordinary vascularization in low-grade NETs and an hypoxia-dependent angiogenesis in high-grade NETs, which is associated to a significant expression of many proangiogenic molecules. Therefore, several antiangiogenic compounds have been tested in these malignancies, and among these, sunitinib has demonstrated activity in pancreatic NET patients by dually targeting the VEGFR and PDGFR pathways. In spite of these efficacious clinical results, apparent resistance to antiangiogenic therapies has been described in NET animal models and in clinical trials. Therefore, overcoming antiangiogenic resistance is a crucial step in the subsequent development of antiangiogenic therapies. Several strategies have been postulated to fight resistance, but preclinical studies and clinical trials will investigate and address these therapeutic approaches in the coming years in order to overcome resistance to antiangiogenic therapies in NETs.
authors.affiliation: Hereditary Cancer Program, Catalan Institute of Oncology-IDIBELL, Barcelona, Spain.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Teulé
authors.forename: Oriol
authors.initials: O
authors.lastname: Casanovas
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D006801:Humans; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000473:pathology; D018358:Neuroendocrine Tumors / Q000098:blood supply* / Q000188:drug therapy; D010190:Pancreatic Neoplasms / Q000098:blood supply* / Q000188:drug therapy
chemical_list: D020533:Angiogenesis Inhibitors