title: Molecular targeted therapy in enteropancreatic neuroendocrine tumors: from biology to clinical practice.
abstract: Advanced enteropancreatic (EP) neuroendocrine tumors (NETs) can be treated with several different therapies, including chemotherapy, biotherapy, and locoregional treatments. Over the last few decades, impressive progress has been made in the biotherapy field. Three main druggable molecular targets have been studied and developed in terms of therapy: somatostatin receptor (sstr), mammalian target of rapamycin (mTOR), and angiogenic factors. In particular, research has moved from the old somatostatin analogs (SSAs), such as octreotide (OCT) and lanreotide (LAN), specifically binding to the sstr-2, to the newer pasireotide (PAS), which presents a wider sstr spectrum. Over the last ten years, several molecular targeted agents (MTAs) have been studied in phase II trials, and very few of them have reached phase III. The mTOR inhibitor everolimus and the multitargeted inhibitor sunitinib have been approved for clinical use by the FDA and EMA in advanced well/moderately-differentiated (WD, MD) progressive pancreatic neuroendocrine tumors (PNETs), on the basis of the positive results of two international large randomized phase III trials vs. placebo. Bevacizumab has been studied in a large US phase III trial vs. interferon (IFN)-alfa2b, and results are pending. In this review, the biological and clinical aspects of MTAs introduced into clinical practice or which are currently in an advanced phase of clinical investigation are addressed.
authors.forename: N
authors.initials: N
authors.lastname: Fazio
authors.forename: A
authors.initials: A
authors.lastname: Scarpa
authors.affiliation: Unit of Gastrointestinal and Neuroendocrine Tumor, European Institute of Oncology, Via Ripamonti 435 20141 Milan, Italy. nicola.fazio@ieo.it.
authors.forename: M
authors.initials: M
authors.lastname: Falconi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods*; D054258:Neural Plate / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D018358:Neuroendocrine Tumors / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents