title: Clinical review: Current scientific rationale for the use of somatostatin analogs and mTOR inhibitors in neuroendocrine tumor therapy.
abstract: BACKGROUND
  Among the innovative molecules used to manage neuroendocrine tumors, there is growing interest in combining the somatostatin analogs octreotide or pasireotide (SOM230) and everolimus (RAD001), an inhibitor that targets the protein kinase mammalian target of rapamycin (mTOR).
  
  
  METHODS
  The aims of this review were to describe the signaling pathways targeted independently by somatostatin analogs and everolimus and to summarize the scientific rationale for the potential additive or synergistic antitumor effects of combined therapy.
  
  
  RESULTS
  The somatostatin analogs (octreotide and lanreotide) have potent inhibitory effects on hypersecretion, thereby alleviating the symptoms associated with neuroendocrine tumors. Furthermore, the antitumor potential of octreotide is now well documented. Pasireotide, a somatostatin analog, has the advantage of targeting a wider range of somatostatin receptors (subtypes 1, 2, 3, and 5) than the analogs previously used in clinical practice (which preferentially target subtype 2) and thus has a broader spectrum of activity. Everolimus is a rapamycin analog that inhibits mTOR, but it is more soluble than rapamycin and can be administered orally. mTOR is a protein kinase involved in many signaling pathways, primarily those initiated by tyrosine kinase receptors. Sustained mTOR activity leads to the induction of cell growth, proliferation, and cell survival. Everolimus therefore has obvious potential in cancer therapy.
  
  
  CONCLUSIONS
  The combination of somatostatin analogs and everolimus in therapeutic trials offers a promising treatment option for neuroendocrine tumors.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche 1037, Cancer Research Center of Toulouse, 1 avenue Jean Poulhès, BP 84225, 31432 Toulouse Cedex 4, France. corinne.bousquet@inserm.fr
authors.forename: Corinne
authors.initials: C
authors.lastname: Bousquet
authors.forename: Charline
authors.initials: C
authors.lastname: Lasfargues
authors.forename: Mounira
authors.initials: M
authors.lastname: Chalabi
authors.forename: Siham Moatassim
authors.initials: SM
authors.lastname: Billah
authors.forename: Christiane
authors.initials: C
authors.lastname: Susini
authors.forename: Delphine
authors.initials: D
authors.lastname: Vezzosi
authors.forename: Philippe
authors.initials: P
authors.lastname: Caron
authors.forename: Stéphane
authors.initials: S
authors.lastname: Pyronnet
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D000068338:Everolimus; D006801:Humans; D018358:Neuroendocrine Tumors / Q000188:drug therapy* / Q000378:metabolism; D015282:Octreotide / Q000627:therapeutic use*; D010456:Peptides, Cyclic / 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; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D000903:Antibiotics, Antineoplastic; D018931:Antineoplastic Agents, Hormonal; D010456:Peptides, Cyclic; C060347:lanreotide; D013004:Somatostatin; D000068338:Everolimus; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D015282:Octreotide; D020123:Sirolimus