title: Novel therapeutic approaches and mechanisms in neuroendocrine tumors: the role of targeted agents.
abstract: Low-intermediate grade neuroendocrine tumors (NETs) are usually slow-growing cancers with a clinical course spanning few to several years managed with active surveillance, locoregional treatments, or somatostain analogs. At some point in their natural history, they develop resistance to these treatments and become more aggressive. Chemotherapy offers only limited therapeutic benefit and any evidence is based on small trials or retrospective studies. The significant progress in molecular biology shed light on the significant role of PI3K/Akt/mTOR pathway and angiogenesis in NETs, while the success of everolimus and sunitinib in landmark clinical trials opened new avenues in the discovery of effective treatments. Ongoing and planned pivotal studies testing newer agents targeting other pathways are underway. In addition to providing better treatment options, these drugs also broadened our understanding of the biology of these tumors. Biomarkers are eagerly needed with the scope of personalizing future treatment.
authors.affiliation: Christie Hospital NHS Foundation Trust, Manchester, M204BX, UK.
authors.forename: George
authors.initials: G
authors.lastname: Papaxoinis
authors.affiliation: Oncology Unit, Third Department of Medicine, University of Athens, Sotiria General Hospital, Athens, Greece.
authors.forename: Kostas
authors.initials: K
authors.lastname: Syrigos
authors.affiliation: Cancer Center, Tufts University School of Medicine, Boston, MA 02111, USA.
authors.forename: Muhammad Wasif
authors.initials: MW
authors.lastname: Saif
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002986:Clinical Trials as Topic; D000068338:Everolimus / Q000627:therapeutic use; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D058990:Molecular Targeted Therapy / Q000379:methods*; D060787:Neoplasm Grading; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D018358:Neuroendocrine Tumors / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D049268:Positron-Emission Tomography; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D011758:Pyrroles / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects*; D013004:Somatostatin / Q000031:analogs & derivatives*; D000077210:Sunitinib; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D000068338:Everolimus; D007211:Indoles; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D047428:Protein Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D011758:Pyrroles; D013004:Somatostatin; D000077210:Sunitinib; D058570:TOR Serine-Threonine Kinases; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; C584390:famitinib; C546842:MTOR protein, human; C494929:PTEN protein, human