title: Advances in the systemic treatment of neuroendocrine tumors in the era of molecular therapy.
abstract: Neuroendocrine tumors (NETs) are heterogeneous in underlying tumor biology and clinical presentations. They are generally classified according to their degree of differentiation and sites of origin. Moreover, NETs are further characterized by their secreted bioactive neuroamine. The treatment paradigm used to be surgical intervention in early disease and mostly palliative nature in the metastatic setting. With an increase in the understanding of the molecular signaling pathways involved in tumor growth, there are various emerging treatment options for patients with advanced NETs. Somatostatin analogs have both anti-tumor effects as well as symptom palliation associated with the secreted neuropeptides. Peptide-radio-receptor treatment (PRRT) using radio-labeled peptides which binds to somatostatin receptor is a useful anti-tumor treatment but limited by general availability. Sunitinib, a multi-targeted tyrosine kinase inhibitor, has recently been shown to improve the survival of pancreatic NETs patients. Similarly, the use of an mTOR inhibitor--everolimus, either alone or in combination with somatostatin analogs have demonstrated encouraging efficacy in treating advanced NETs. The success of these two agents in pancreatic NETS supports the notion that targeting angiogenesis and/or PI3K/AKT/mTOR pathway is an important strategy for making therapeutic advances in this disease. There are now many ongoing trials in exploring the role of other novel agents in treating patients with pancreatic NETs or carcinoid. The major plaguing problem in this era is the differential response to biological agents amongst NETs of different anatomical origins. Pancreatic NETs are generally more responsive to both chemotherapy and targeted agents than NETs of other sites. Thus, the development of potential predictive and prognostic biomarkers to tailor various molecular therapies to different NETs populations is a major unmet need.
authors.affiliation: Department of Medicine, Queen Mary Hospital, Hong Kong SAR, China.
authors.forename: Roland
authors.initials: R
authors.lastname: Leung
authors.forename: Brian
authors.initials: B
authors.lastname: Lang
authors.forename: Hilda
authors.initials: H
authors.lastname: Wong
authors.forename: Joanne
authors.initials: J
authors.lastname: Chiu
authors.forename: Wan K
authors.initials: WK
authors.lastname: Yat
authors.forename: Tony
authors.initials: T
authors.lastname: Shek
authors.forename: Woo Y
authors.initials: WY
authors.lastname: Cho
authors.forename: Lo C
authors.initials: LC
authors.lastname: Yau
authors.forename: Thomas
authors.initials: T
authors.lastname: Yau
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018278:Carcinoma, Neuroendocrine / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D000068338:Everolimus; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D058990:Molecular Targeted Therapy; D018358:Neuroendocrine Tumors / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D011758:Pyrroles / Q000627:therapeutic use; D019275:Radiopharmaceuticals / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000031:analogs & derivatives / Q000627:therapeutic use; D013004:Somatostatin / Q000031:analogs & derivatives / Q000627:therapeutic use; D000077210:Sunitinib; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D000068338:Everolimus; D007211:Indoles; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D011758:Pyrroles; D019275:Radiopharmaceuticals; D020123:Sirolimus; D013004:Somatostatin; D000077210:Sunitinib; D058570:TOR Serine-Threonine Kinases; C546842:MTOR protein, human