title: Innovations therapy: mammalian target of rapamycin (mTOR) inhibitors for the treatment of neuroendocrine tumors.
abstract: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare neoplasms that require a multidisciplinary approach for an optimal management. The lack of effectiveness of traditional DNA-damaging agents has led to the exploration of new targeted drugs in order to exploit phenotypical features of GEP-NET therapy. However, due to the orphan setting of these tumors, deeper characterization of molecular features and pathways that characterize cell growth, apoptosis, angiogenesis, and invasion are lacking, particularly genetic mutations or epigenetic alterations that generate oncogenic dependency or even addiction. The PI3K-AKT-mTOR pathway has been implicated as having a crucial role in GEP-NETs not only due to the overexpression of several growth factors and their receptors that finally activate this axis but also hereditary syndromes with constitutive activation of the mTOR pathway with high incidence of GEP-NETs. In this article, we aim to review the recent development of the main molecules that target mTOR complex and have showed promising activity in the treatment of GEPNETs.
authors.affiliation: Medical Oncology Department, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain. jacapdevila@vhebron.net
authors.forename: Jaume
authors.initials: J
authors.lastname: Capdevila
authors.forename: Ramón
authors.initials: R
authors.lastname: Salazar
authors.forename: Irene
authors.initials: I
authors.lastname: Halperín
authors.forename: Albert
authors.initials: A
authors.lastname: Abad
authors.forename: James C
authors.initials: JC
authors.lastname: Yao
mesh_terms: D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006801:Humans; D018358:Neuroendocrine Tumors / Q000188:drug therapy*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D058570:TOR Serine-Threonine Kinases