title: PI3K/Akt/mTOR signaling in medullary thyroid cancer: a promising molecular target for cancer therapy.
abstract: The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway is a central hub for the regulation of cell proliferation, apoptosis, cell cycle, metabolism, and angiogenesis. Several studies have recently suggested that the PI3K/Akt/mTOR signaling pathway is implicated in the pathogenesis and progression of neuroendocrine tumors. Medullary thyroid cancer (MTC) is a neuroendocrine tumor developing from the C cells of the thyroid. Mutations in the RET proto-oncogene are involved in the pathogenesis of several forms of MTC. The deregulation of the PI3K/Akt/mTOR pathway seems to contribute to the tumorigenic activity of RET proto-oncogene mutations. Targeting this pathway through specific inhibitors at simple or multiple sites may represent an attractive potential therapeutic approach for patients with advanced MTCs. The aim of this review is to examine the role of the PI3K/Akt/mTOR pathway in the development and progression of MTC and the new therapeutic options that target this signaling pathway.
authors.affiliation: Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
authors.forename: Gloria Irene
authors.initials: GI
authors.lastname: Manfredi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Dicitore
authors.forename: Germano
authors.initials: G
authors.lastname: Gaudenzi
authors.forename: Michele
authors.initials: M
authors.lastname: Caraglia
authors.forename: Luca
authors.initials: L
authors.lastname: Persani
authors.forename: Giovanni
authors.initials: G
authors.lastname: Vitale
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018278:Carcinoma, Neuroendocrine / Q000188:drug therapy*; D006801:Humans; D000081082:Phosphoinositide-3 Kinase Inhibitors; D000090063:Proto-Oncogene Mas; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D013964:Thyroid Neoplasms / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; C000715470:MAS1 protein, human; D000081082:Phosphoinositide-3 Kinase Inhibitors; D000090063:Proto-Oncogene Mas; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases