Current scientific rationale for the use of somatostatin analogs and mTOR inhibitors in neuroendocrine tumor therapy

Journal of Clinical Endocrinology and Metabolism

Volumn 97, Issue 3, 2012, Pages 727-737

  Bousquet, Corinne ^a   Lasfargues, Charline ^a   Chalabi, Mounira ^a   Billah, Siham Moatassim ^a   Susini, Christiane ^a   Vezzosi, Delphine ^b   Caron, Philippe ^b   Pyronnet, Stéphane ^a  

^a CANCER RESEARCH CENTER OF TOULOUSE   (France)

^b SERVICE DE PNEUMOLOGIE   (France)

Author keywords

[No Author keywords available]

Indexed keywords

ANGIOPEPTIN; CHOLECYSTOKININ; CORTICOTROPIN; EVEROLIMUS; FIBROBLAST GROWTH FACTOR; GASTRIN; GLUCAGON; GROWTH HORMONE; INITIATION FACTOR 4E; INITIATION FACTOR 4E BINDING PROTEIN 1; INITIATION FACTOR 4G; INSULIN; MAMMALIAN TARGET OF RAPAMYCIN; MAMMALIAN TARGET OF RAPAMYCIN INHIBITOR; OCTREOTIDE; PASIREOTIDE; PLACEBO; PROTEIN P70; RAPAMYCIN; SECRETIN; SOMATOSTATIN DERIVATIVE; SOMATOSTATIN RECEPTOR 1; SOMATOSTATIN RECEPTOR 2; SOMATOSTATIN RECEPTOR 3; SOMATOSTATIN RECEPTOR 5; THYROTROPIN; TYROSINE KINASE RECEPTOR; UNINDEXED DRUG; VASCULOTROPIN; VASOACTIVE INTESTINAL POLYPEPTIDE; ANTINEOPLASTIC ANTIBIOTIC; ANTINEOPLASTIC HORMONE AGONISTS AND ANTAGONISTS; CYCLOPEPTIDE; DRUG DERIVATIVE; MTOR PROTEIN, HUMAN; SOMATOSTATIN; TARGET OF RAPAMYCIN KINASE;

ANTIANGIOGENIC ACTIVITY; ANTINEOPLASTIC ACTIVITY; ANTIPROLIFERATIVE ACTIVITY; APHTHOUS ULCER; APOPTOSIS; CANCER INHIBITION; CELL GROWTH; CELL PROLIFERATION; CELL SURVIVAL; DRUG HALF LIFE; DRUG POTENTIATION; DRUG RECEPTOR BINDING; DRUG TARGETING; HORMONE INHIBITION; HUMAN; MONOTHERAPY; NEUROENDOCRINE TUMOR; NONHUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PROTEIN SYNTHESIS INHIBITION; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SIGNAL TRANSDUCTION; STOMATITIS; DRUG EFFECT; METABOLISM;

MAMMALIA;

ANTIBIOTICS, ANTINEOPLASTIC; ANTINEOPLASTIC AGENTS, HORMONAL; HUMANS; NEUROENDOCRINE TUMORS; OCTREOTIDE; PEPTIDES, CYCLIC; SIGNAL TRANSDUCTION; SIROLIMUS; SOMATOSTATIN; TOR SERINE-THREONINE KINASES;

EID: 84858055749     PISSN: 0021972X     EISSN: 19457197     Source Type: Journal    
DOI: 10.1210/jc.2011-2088     Document Type: Review

References (91)

1. Schmid HA 2008 Pasireotide (SOM230): development, mechanism of action and potential applications. Mol Cell Endocrinol 286: 69-74 (Pubitemid 351680237)
2. Ma P, Wang Y, van der Hoek J, Nedelman J, Schran H, Tran LL, Lamberts SW 2005 Pharmacokinetic-pharmacodynamic comparison of a novel multiligand somatostatin analog, SOM230, with octreotide in patients with acromegaly. Clin Pharmacol Ther 78: 69-80 (Pubitemid 40956933)
3. Oberg KE, Reubi JC, Kwekkeboom DJ, Krenning EP 2010 Role of somatostatins in gastroenteropancreatic neuroendocrine tumor development and therapy. Gastroenterology 139:742-753, 753.e1
4. de Herder WW, Hofland LJ, van der Lely AJ, Lamberts SW 2003 Somatostatin receptors in gastroentero-pancreatic neuroendocrine tumours. Endocr Relat Cancer 10:451-458 (Pubitemid 38094881)
5. Schmid HA, Schoeffter P 2004 Functional activity of the multiligand analog SOM230 at human recombinant somatostatin receptor subtypes supports its usefulness in neuroendocrine tumors. Neuroendocrinology 80(Suppl 1):47-50
6. O'Toole D, Saveanu A, Couvelard A, Gunz G, Enjalbert A, Jaquet P, Ruszniewski P, Barlier A 2006 The analysis of quantitative expression of somatostatin and dopamine receptors in gastro-enteropancreatic tumours opens new therapeutic strategies. Eur J Endocrinol 155:849-857
7. Reubi JC 2007 Peptide receptor expression in GEP-NET. Virchows Arch 451(Suppl 1):S47-S50 (Pubitemid 47283376)
8. Asnacios A, Courbon F, Rochaix P, Bauvin E, Cances-Lauwers V, Susini C, Schulz S, Boneu A, Guimbaud R, Buscail L 2008 Indium-111-pentetreotide scintigraphy and somatostatin receptor subtype 2 expression: new prognostic factors for malignant well-differentiated endocrine tumors. J Clin Oncol 26:963-970 (Pubitemid 351398091)
9. Corleto VD, Falconi M, Panzuto F, Milione M, De Luca O, Perri P, Cannizzaro R, Bordi C, Pederzoli P, Scarpa A, Delle Fave G 2009 Somatostatin receptor subtypes 2 and 5 are associated with better survival in well-differentiated endocrine carcinomas. Neuroendocrinology 89:223-230
10. O'Toole D, Ducreux M, Bommelaer G, Wemeau JL, Bouché O, Catus F, Blumberg J, Ruszniewski P 2000 Treatment of carcinoid syndrome: a prospective crossover evaluation of lanreotide versus octreotide in terms of efficacy, patient acceptability, and tolerance. Cancer 88:770-776 (Pubitemid 30091095)
11. Rubin J, Ajani J, Schirmer W, Venook AP, Bukowski R, Pommier R, Saltz L, Dandona P, Anthony L 1999 Octreotide acetate long-acting formulation versus open-label subcutaneous octreotide acetate in malignant carcinoid syndrome. J Clin Oncol 17:600-606 (Pubitemid 29075248)
12. Lamberts SW, de Herder WW, Hofland LJ 2002 Somatostatin analogs in the diagnosis and treatment of cancer. Trends Endocrinol Metab 13:451-457 (Pubitemid 36733940)
13. Bruns C, Lewis I, Briner U, Meno-Tetang G, Weckbecker G 2002 SOM230: a novel somatostatin peptidomimetic with broad somatotropin release inhibiting factor (SRIF) receptor binding and a unique antisecretory profile. Eur J Endocrinol 146:707-716 (Pubitemid 34552506)
14. Petersenn S, Schopohl J, Barkan A, Mohideen P, Colao A, Abs R, Buchelt A, Ho YY, Hu K, Farrall AJ, Melmed S, Biller BM 2010 Pasireotide (SOM230) demonstrates efficacy and safety in patients with acromegaly: a randomized, multicenter, phase II trial. J Clin Endocrinol Metab 95:2781-2789
15. van der Hoek J, de Herder WW, Feelders RA, van der Lely AJ, Uitterlinden P, Boerlin V, Bruns C, Poon KW, Lewis I, Weckbecker G, Krahnke T, Hofland LJ, Lamberts SW 2004 A single-dose comparison of the acute effects between the new somatostatin analog SOM230 and octreotide in acromegalic patients. J Clin Endocrinol Metab 89:638-645 (Pubitemid 38269871)
16. Schmid HA, Silva AP 2005 Short- and long-term effects of octreotide and SOM230 on GH, IGF-I, ACTH, corticosterone and ghrelin in rats. J Endocrinol Invest 28(11 Suppl International):28-35
17. Lesche S, Lehmann D, Nagel F, Schmid HA, Schulz S 2009 Differential effects of octreotide and pasireotide on somatostatin receptor internalization and trafficking in vitro. J Clin Endocrinol Metab 94:654-661
18. Waser B, Cescato R, Tamma ML, Maecke HR, Reubi JC 2010 Absence of somatostatin SST(2) receptor internalization in vivo after intravenous SOM230 application in the AR42J animal tumor model. Eur J Pharmacol 644:257-262
19. Arnold R, Simon B, Wied M 2000 Treatment of neuroendocrine GEP tumours with somatostatin analogues: a review. Digestion 62(Suppl 1):84-91
20. Rinke A, Müller HH, Schade-Brittinger C, Klose KJ, Barth P, Wied M, Mayer C, Aminossadati B, Pape UF, Bläker M, Harder J, Arnold C, Gress T, Arnold R 2009 Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID Study Group. J Clin Oncol 27:4656-4663
21. Cozzi R, Montini M, Attanasio R, Albizzi M, Lasio G, Lodrini S, Doneda P, Cortesi L, Pagani G 2006 Primary treatment of acromegaly with octreotide LAR: a long-term (up to nine years) prospective study of its efficacy in the control of disease activity and tumor shrinkage. J Clin Endocrinol Metab 91:1397-1403
22. Resmini E, Dadati P, Ravetti JL, Zona G, Spaziante R, Saveanu A, Jaquet P, Culler MD, Bianchi F, Rebora A, Minuto F, Ferone D 2007 Rapid pituitary tumor shrinkage with dissociation between antiproliferative and antisecretory effects of a long-acting octreotide in an acromegalic patient. J Clin Endocrinol Metab 92:1592-1599 (Pubitemid 46997156)
23. Casarini AP, Pinto EM, Jallad RS, Giorgi RR, Giannella-Neto D, Bronstein MD 2006 Dissociation between tumor shrinkage and hormonal response during somatostatin analog treatment in an acromegalic patient: preferential expression of somatostatin receptor subtype 3. J Endocrinol Invest 29:826-830 (Pubitemid 44872594)
24. Pyronnet S, Bousquet C, Najib S, Azar R, Laklai H, Susini C 2008 Antitumor effects of somatostatin. Mol Cell Endocrinol 286:230-237
25. Bousquet C, Guillermet-Guibert J, Saint-Laurent N, Archer-Lahlou E, Lopez F, Fanjul M, Ferrand A, Fourmy D, Pichereaux C, Monsarrat B, Pradayrol L, Estève JP, Susini C 2006 Direct binding of p85 to sst2 somatostatin receptor reveals a novel mechanism for inhibiting PI3K pathway. EMBO J 25:3943-3954 (Pubitemid 44338737)
26. Bousquet C, Delesque N, Lopez F, Saint-Laurent N, Estève JP, Bedecs K, Buscail L, Vaysse N, Susini C 1998 sst2 somatostatin receptor mediates negative regulation of insulin receptor signaling through the tyrosine phosphatase SHP-1. J Biol Chem 273:7099-7106 (Pubitemid 28160380)
27. Barbieri F, Pattarozzi A, Gatti M, Porcile C, Bajetto A, Ferrari A, Culler MD, Florio T 2008 Somatostatin receptors 1, 2, and 5 cooperate in the somatostatin inhibition of C6 glioma cell proliferation in vitro via a phosphotyrosine phosphatase-η-dependent inhibition of extracellularly regulated kinase-1/2. Endocrinology 149:4736-4746
28. Lahlou H, Saint-Laurent N, Estève JP, Eychène A, Pradayrol L, Pyronnet S, Susini C 2003 sst2 Somatostatin receptor inhibits cell proliferation through Ras-, Rap1-, and B-Raf-dependent ERK2 activation. J Biol Chem 278:39356-39371 (Pubitemid 37248491)
29. Lahlou H, Fanjul M, Pradayrol L, Susini C, Pyronnet S 2005 Restoration of functional gap junctions through internal ribosome entry site-dependent synthesis of endogenous connexins in density-inhibited cancer cells. Mol Cell Biol 25:4034-4045 (Pubitemid 40617652)
30. Guillermet J, Saint-Laurent N, Rochaix P, Cuvillier O, Levade T, Schally AV, Pradayrol L, Buscail L, Susini C, Bousquet C 2003 Somatostatin receptor subtype 2 sensitizes human pancreatic cancer cells to death ligand-induced apoptosis. Proc Natl Acad Sci USA 100:155-160 (Pubitemid 36078044)
31. Pasquali D, Rossi V, Conzo G, Pannone G, Bufo P, De Bellis A, Renzullo A, Bellastella G, Colao A, Vallone G, Bellastella A, Sinisi AA 2008 Effects of somatostatin analog SOM230 on cell proliferation, apoptosis, and catecholamine levels in cultured pheochromocytoma cells. J Mol Endocrinol 40:263-271 (Pubitemid 351865034)
32. Murray RD, Kim K, Ren SG, Chelly M, Umehara Y, Melmed S 2004 Central and peripheral actions of somatostatin on the growth hormone-IGF-I axis. J Clin Invest 114:349-356 (Pubitemid 39071607)
33. Albini A, Florio T, Giunciuglio D, Masiello L, Carlone S, Corsaro A, Thellung S, Cai T, Noonan DM, Schettini G 1999 Somatostatin controls Kaposi's sarcoma tumor growth through inhibition of angiogenesis. FASEB J 13:647-655 (Pubitemid 29156396)
34. Arena S, Pattarozzi A, Corsaro A, Schettini G, Florio T 2005 Somatostatin receptor subtype-dependent regulation of nitric oxide release: involvement of different intracellular pathways. Mol Endocrinol 19:255-267 (Pubitemid 40065974)
35. Mentlein R, Eichler O, Forstreuter F, Held-Feindt J 2001 Somatostatin inhibits the production of vascular endothelial growth factor in human glioma cells. Int J Cancer 92:545-550 (Pubitemid 32319428)
36. Zatelli MC, Piccin D, Vignali C, Tagliati F, Ambrosio MR, Bondanelli M, Cimino V, Bianchi A, Schmid HA, Scanarini M, Pontecorvi A, De Marinis L, Maira G, degli Uberti EC 2007 Pasireotide, a multiple somatostatin receptor subtypes ligand, reduces cell viability in non-functioning pituitary adenomas by inhibiting vascular endothelial growth factor secretion. Endocr Relat Cancer 14:91-102
37. Cascinu S, Del Ferro E, Ligi M, Staccioli MP, Giordani P, Catalano V, Agostinelli R, Muretto P, Catalano G 2001 Inhibition of vascular endothelial growth factor by octreotide in colorectal cancer patients. Cancer Invest 19:8-12 (Pubitemid 32233796)
38. Laklai H, Laval S, Dumartin L, Rochaix P, Hagedorn M, Bikfalvi A, Le Guellec S, Delisle MB, Schally AV, Susini C, Pyronnet S, Bousquet C 2009 Thrombospondin-1 is a critical effector of oncosuppressive activity of sst2 somatostatin receptor on pancreatic cancer. Proc Natl Acad Sci USA 106:17769-17774
39. Denzler B, Reubi JC 1999 Expression of somatostatin receptors in peritumoral veins of human tumors. Cancer 85:188-198 (Pubitemid 29031374)
40. Watson JC, Balster DA, Gebhardt BM, O'Dorisio TM, O'Dorisio MS, Espenan GD, Drouant GJ, Woltering EA 2001 Growing vascular endothelial cells express somatostatin subtype 2 receptors. Br J Cancer 85:266-272 (Pubitemid 32695750)
41. Adams RL, Adams IP, Lindow SW, Zhong W, Atkin SL 2005 Somatostatin receptors 2 and 5 are preferentially expressed in proliferating endothelium. Br J Cancer 92:1493-1498 (Pubitemid 40705017)
42. Ballou LM, Lin RZ 2008 Rapamycin and mTOR kinase inhibitors. J Chem Biol 1:27-36
43. DeBerardinis RJ, Lum JJ, Hatzivassiliou G, Thompson CB 2008 The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. Cell Metab 7:11-20
44. Loewith R, Jacinto E, Wullschleger S, Lorberg A, Crespo JL, Bonenfant D, Oppliger W, Jenoe P, Hall MN 2002 Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control. Mol Cell 10:457-468 (Pubitemid 35284167)
45. Nojima H, Tokunaga C, Eguchi S, Oshiro N, Hidayat S, Yoshino K, Hara K, Tanaka N, Avruch J, Yonezawa K 2003 The mammalian target of rapamycin (mTOR) partner, raptor, binds the mTOR substrates p70 S6 kinase and 4E-BP1 through their TOR signaling (TOS) motif. J Biol Chem 278:15461-15464 (Pubitemid 36799651)
46. Roberg KJ, Bickel S, Rowley N, Kaiser CA 1997 Control of amino acid permease sorting in the late secretory pathway of Saccharomyces cerevisiae by SEC13, LST4, LST7 and LST8. Genetics 147: 1569-1584 (Pubitemid 27525454)
47. Kaiser CA, Schekman R 1990 Distinct sets of SEC genes govern transport vesicle formation and fusion early in the secretory pathway. Cell 61:723-733
48. Jacinto E, Loewith R, Schmidt A, Lin S, Rüegg MA, Hall A, Hall MN 2004 Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive. Nat Cell Biol 6:1122-1128 (Pubitemid 39468014)
49. Levy S, Avni D, Hariharan N, Perry RP, Meyuhas O 1991 Oligopyrimidine tract at the 5′ end of mammalian ribosomal protein mRNAsis required for their translational control. Proc Natl Acad Sci USA 88:3319-3323 (Pubitemid 21916612)
50. Hamilton TL, Stoneley M, Spriggs KA, Bushell M 2006 TOPs and their regulation. Biochem Soc Trans 34:12-16 (Pubitemid 43235523)
51. Lin TA, Kong X, Haystead TA, Pause A, Belsham G, Sonenberg N, Lawrence Jr JC 1994 PHAS-I as a link between mitogen-activated protein kinase and translation initiation. Science 266:653-656 (Pubitemid 24363524)
52. Svitkin YV, Pause A, Haghighat A, Pyronnet S, Witherell G, Belsham GJ, Sonenberg N 2001 The requirement for eukaryotic initiation factor 4A (elF4A) in translation is in direct proportion to the degree of mRNA 5′ secondary structure. RNA 7:382-394 (Pubitemid 32381914)
53. Pickering BM, Willis AE 2005 The implications of structured 5′ untranslated regions on translation and disease. Semin Cell Dev Biol 16:39-47 (Pubitemid 40126875)
54. Pyronnet S, Sonenberg N 2001 Cell-cycle-dependent translational control. Curr Opin Genet Dev 11:13-18 (Pubitemid 32119272)
55. She QB, Halilovic E, Ye Q, Zhen W, Shirasawa S, Sasazuki T, Solit DB, Rosen N 2010 4E-BP1 is a key effector of the oncogenic activation of the AKT and ERK signaling pathways that integrates their function in tumors. Cancer Cell 18:39-51
56. Petroulakis E, Parsyan A, Dowling RJ, LeBacquer O, Martineau Y, Bidinosti M, Larsson O, Alain T, Rong L, Mamane Y, Paquet M, Furic L, Topisirovic I, Shahbazian D, Livingstone M, Costa-Mattioli M, Teodoro JG, Sonenberg N 2009 p53-dependent translational control of senescence and transformation via 4E-BPs. Cancer Cell 16:439-446
57. Vézina C, Kudelski A, Sehgal SN 1975 Rapamycin (AY-22,989), a new antifungal antibiotic. I: Taxonomy of the producing streptomycete and isolation of the active principle. J Antibiot (Tokyo) 28: 721-726
58. Cafferkey R, Young PR, McLaughlin MM, Bergsma DJ, Koltin Y, Sathe GM, Faucette L, Eng WK, Johnson RK, Livi GP 1993 Dominant missense mutations in a novel yeast protein related to mammalian phosphatidylinositol 3-kinase and VPS34 abrogate rapamycin cytotoxicity. Mol Cell Biol 13:6012-6023 (Pubitemid 23292596)
59. Brown EJ, Albers MW, Shin TB, Ichikawa K, Keith CT, Lane WS, Schreiber SL 1994 A mammalian protein targeted by G1-arresting rapamycin-receptor complex. Nature 369:756-758
60. Sabatini DM, Erdjument-Bromage H, Lui M, Tempst P, Snyder SH 1994 RAFT1: a mammalian protein that binds to FKBP12 in a rapamycin-dependent fashion and is homologous to yeast TORs. Cell 78:35-43 (Pubitemid 24228298)
61. Figlin RA, Brown E, Armstrong AJ, Akerley W, Benson III AB, Burstein HJ, Ettinger DS, Febbo PG, Fury MG, Hudes GR, Kies MS, Kwak EL, Morgan Jr RJ, Mortimer J, Reckamp K, Venook AP, Worden F, Yen Y 2008 NCCN Task Force Report: mTOR inhibition in solid tumors. J Natl Compr Canc Netw 6(Suppl 5):S1-S20
62. Meric-Bernstam F, Gonzalez-Angulo AM 2009 Targeting the mTORsignaling network for cancer therapy. J Clin Oncol 27:2278-2287
63. O'Reilly T, McSheehy PM, Wartmann M, Lassota P, Brandt R, Lane HA 2011 Evaluation of the mTOR inhibitor, everolimus, in combination with cytotoxic antitumor agents using human tumor models in vitro and in vivo. Anticancer Drugs 22:58-78
64. Zeng Z, Sarbassov dos D, Samudio IJ, Yee KW, Munsell MF, Ellen Jackson C, Giles FJ, Sabatini DM, Andreeff M, Konopleva M 2007 Rapamycin derivatives reduce mTORC2 signaling and inhibit AKT activation in AML. Blood 109:3509-3512
65. Houghton PJ 2010 Everolimus. Clin Cancer Res 16:1368-1372
66. Borders EB, Bivona C, Medina PJ 2010 Mammalian target of rapamycin: biological function and target for novel anticancer agents. Am J Health Syst Pharm 67:2095-2106
67. Faivre S, Kroemer G, Raymond E 2006 Current development of mTORinhibitors as anticancer agents. Nat Rev Drug Discov 5:671-688 (Pubitemid 44151605)
68. Jensen RT, Berna MJ, Bingham DB, Norton JA 2008 Inherited pancreatic endocrine tumor syndromes: advances in molecular pathogenesis, diagnosis, management, and controversies. Cancer 113(7 Suppl):1807-1843
69. Missiaglia E, Dalai I, Barbi S, Beghelli S, Falconi M, della Peruta M, Piemonti L, Capurso G, Di Florio A, delle Fave G, Pederzoli P, Croce CM, Scarpa A 2010 Pancreatic endocrine tumors: expression profiling evidences a role for AKT-mTOR pathway. J Clin Oncol 28: 245-255
70. Yao JC, Lombard-Bohas C, Baudin E, Kvols LK, Rougier P, Ruszniewski P, Hoosen S, St Peter J, Haas T, Lebwohl D, Van Cutsem E, Kulke MH, Hobday TJ, O'Dorisio TM, Shah MH, Cadiot G, Luppi G, Posey JA, Wiedenmann B 2010 Daily oral everolimus activity in patients with metastatic pancreatic neuroendocrine tumors after failure of cytotoxic chemotherapy: a phase II trial. J Clin Oncol 28:69-76
71. Yao JC, Phan AT, Chang DZ, Wolff RA, Hess K, Gupta S, Jacobs C, Mares JE, Landgraf AN, Rashid A, Meric-Bernstam F 2008 Efficacy of RAD001 (everolimus) and octreotide LAR in advanced low- to intermediate-grade neuroendocrine tumors: results of a phase II study. J Clin Oncol 26:4311-4318
72. Pavel ME, Hainsworth JD, Baudin E, Peeters M, Hoersch D, Winkler RE, Klimovsky J, Lebwohl D, Jehl V, Wolin EM, Oberg K, Van Cutsem E, Yao JC, for the RADIANT-2 Study Group 25 November 2011 Everolimus plus octreotide long-acting repeatable for the treatment of advanced neuroendocrine tumours associated with carcinoid syndrome (RADIANT-2): a randomized, placebo-controlled, phase 3 study. Lancet doi: 10.1016/S0140-6736(11)61742-X
73. Yao JC, Shah MH, Ito T, Bohas CL, Wolin EM, Van Cutsem E, Hobday TJ, Okusaka T, Capdevila J, de Vries EG, Tomassetti P, Pavel ME, Hoosen S, Haas T, Lincy J, Lebwohl D, Öberg K 2011 Everolimus for advanced pancreatic neuroendocrine tumors.NEngl J Med 364:514-523
74. Oberg KE 9 September 2011 The management of neuroendocrine tumours: current and future medical therapy options. Clin Oncol (R Coll Radiol) doi: 10.1016/j.clon.2011.08.006
75. Druce MR, Kaltsas GA, Fraenkel M, Gross DJ, Grossman AB 2009 Novel and evolving therapies in the treatment of malignant phaeochromocytoma: experience with the mTOR inhibitor everolimus (RAD001). Horm Metab Res 41:697-702
76. Wolpin BM, Hezel AF, Abrams T, Blaszkowsky LS, Meyerhardt JA, Chan JA, Enzinger PC, Allen B, Clark JW, Ryan DP, Fuchs CS 2009 Oral mTOR inhibitor everolimus in patients with gemcitabine-refractory metastatic pancreatic cancer. J Clin Oncol 27:193-198
77. Di Nicolantonio F, Arena S, Tabernero J, Grosso S, Molinari F, Macarulla T, Russo M, Cancelliere C, Zecchin D, Mazzucchelli L, Sasazuki T, Shirasawa S, Geuna M, Frattini M, Baselga J, Gallicchio M, Biffo S, Bardelli A 2010 Deregulation of the PI3K and KRAS signaling pathways in human cancer cells determines their response to everolimus. J Clin Invest 120:2858-2866
78. Wan X, Harkavy B, Shen N, Grohar P, Helman LJ 2007 Rapamycin induces feedback activation of Akt signaling through an IGF-1R-dependent mechanism. Oncogene 26:1932-1940 (Pubitemid 46474636)
79. O'Reilly KE, Rojo F, She QB, Solit D, Mills GB, Smith D, Lane H, Hofmann F, Hicklin DJ, Ludwig DL, Baselga J, Rosen N 2006 mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt. Cancer Res 66:1500-1508 (Pubitemid 43259931)
80. Tabernero J, Rojo F, Calvo E, Burris H, Judson I, Hazell K, Martinelli E, Ramon y Cajal S, Jones S, Vidal L, Shand N, Macarulla T, Ramos FJ, Dimitrijevic S, Zoellner U, Tang P, Stumm M, Lane HA, Lebwohl D, Baselga J 2008 Dose- and schedule-dependent inhibition of the mammalian target of rapamycin pathway with everolimus: a phase I tumor pharmacodynamic study in patients with advanced solid tumors. J Clin Oncol 26:1603-1610
81. Haruta T, Uno T, Kawahara J, Takano A, Egawa K, Sharma PM, Olefsky JM, Kobayashi M 2000 A rapamycin-sensitive pathway down-regulates insulin signaling via phosphorylation and proteasomal degradation of insulin receptor substrate-1. Mol Endocrinol 14:783-794 (Pubitemid 32260492)
82. Sun SY, Rosenberg LM, Wang X, Zhou Z, Yue P, Fu H, Khuri FR 2005 Activation of Akt and eIF4E survival pathways by rapamycin-mediated mammalian target of rapamycin inhibition. Cancer Res 65:7052-7058 (Pubitemid 41161231)
83. Shi Y, Yan H, Frost P, Gera J, Lichtenstein A 2005 Mammalian target of rapamycin inhibitors activate the AKT kinase in multiple myeloma cells by up-regulating the insulin-like growth factor receptor/insulin receptor substrate-1/phosphatidylinositol 3-kinase cascade. Mol Cancer Ther 4:1533-1540 (Pubitemid 41556435)
84. Oberstein PE, Saif MW 2011 Novel agents in the treatment of unresectable neuroendocrine tumors. Highlights from the "2011 ASCO Annual Meeting." Chicago, IL, USA; June 3-7, 2011. JOP 12:358-361
85. Cerovac V, Monteserin-Garcia J, Rubinfeld H, Buchfelder M, Losa M, Florio T, Paez-Pereda M, Stalla GK, Theodoropoulou M 2010 The somatostatin analogue octreotide confers sensitivity to rapamycin treatment on pituitary tumor cells. Cancer Res 70:666-674
86. Zatelli MC, Minoia M, Filieri C, Tagliati F, Buratto M, Ambrosio MR, Lapparelli M, Scanarini M, Degli Uberti EC 2010 Effect of everolimus on cell viability in nonfunctioning pituitary adenomas. J Clin Endocrinol Metab 95:968-976
87. Ruan W, Fahlbusch F, Clemmons DR, Monaco ME, Walden PD, Silva AP, Schmid HA, Kleinberg DL 2006 SOM230 inhibits insulin-like growth factor-I action in mammary gland development by pituitary independent mechanism: mediated through somatostatin subtype receptor 3? Mol Endocrinol 20:426-436 (Pubitemid 43152515)
88. Azar R, Najib S, Lahlou H, Susini C, Pyronnet S 2008 Phosphatidylinositol 3-kinase-dependent transcriptional silencing of the translational repressor 4E-BP1. Cell Mol Life Sci 65:3110-3117
89. Villaume K, Blanc M, Gouysse G, Walter T, Couderc C, Nejjari M, Vercherat C, Cordier-Bussat M, Roche C, Scoazec JY 2010 VEGF secretion by neuroendocrine tumor cells is inhibited by octreotide and by inhibitors of the PI3K/AKT/mTOR pathway. Neuroendocrinology 91:268-278
90. Moreno A, Akcakanat A, Munsell MF, Soni A, Yao JC, Meric- Bernstam F 2008 Antitumor activity of rapamycin and octreotide as single agents or in combination in neuroendocrine tumors. Endocr Relat Cancer 15:257-266
91. Svejda B, Kidd M, Kazberouk A, Lawrence B, Pfragner R, Modlin IM 2011 Limitations in small intestinal neuroendocrine tumor therapy by mTOR kinase inhibition reflect growth factor-mediated PI3K feedback loop activation via ERK1/2 and AKT. Cancer 117: 4141-4154