title: Suppression of mTOR pathway in solid tumors: lessons learned from clinical experience in renal cell carcinoma and neuroendocrine tumors and new perspectives.
abstract: The PI3K-AKT-mTOR pathway plays role in the regulation of many cellular processes. Hyperactivation of mTOR signaling has been implicated in human carcinogenesis, representing an attractive target for cancer therapy. Among other cancer subtypes, renal cell carcinoma (RCC) and neuroendocrine tumors are relevant settings in which the deregulation of mTOR pathway is of crucial importance. Different mTOR-inhibitory agents have been developed in recent years. Temsirolimus is approved for advanced RCC; everolimus is registered for the treatment of advanced RCC, pancreatic neuroendocrine tumors and postmenopausal, hormone receptor-positive/HER2-negative, advanced breast cancer. This review is focused on the description of the clinical experience with mTOR-inhibitor agents for the treatment of advanced RCC and neuroendocrine tumors, followed by an excursus on the landscape of the ongoing research in this field.
authors.affiliation: Medical Oncology, Azienda Ospedaliera Universitaria Integrata, University of Verona, Piazzale LA Scuro 10, 37124 Verona, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Ortolani
authors.affiliation: Medical Oncology, Azienda Ospedaliera Universitaria Integrata, University of Verona, Piazzale LA Scuro 10, 37124 Verona, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Ciccarese
authors.affiliation: Medical Oncology, Azienda Ospedaliera Universitaria Integrata, University of Verona, Piazzale LA Scuro 10, 37124 Verona, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Cingarlini
authors.affiliation: Medical Oncology, Azienda Ospedaliera Universitaria Integrata, University of Verona, Piazzale LA Scuro 10, 37124 Verona, Italy.
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Tortora
authors.affiliation: Medical Oncology, Azienda Ospedaliera Universitaria Integrata, University of Verona, Piazzale LA Scuro 10, 37124 Verona, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Massari
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000378:metabolism; D002986:Clinical Trials as Topic; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D000076222:Mechanistic Target of Rapamycin Complex 1; D058990:Molecular Targeted Therapy; D046912:Multiprotein Complexes / Q000037:antagonists & inhibitors / Q000378:metabolism; D018358:Neuroendocrine Tumors / Q000188:drug therapy* / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D046912:Multiprotein Complexes; C546842:MTOR protein, human; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases
keywords: everolimus; mTOR inhibitors; mTOR pathway; neuroendocrine neoplasm; renal cell carcinoma; temsirolimus