1. Cives M, Strosberg J. An update on gastroenteropancreatic neuroendocrine tumours. Oncology (Williston Park) 2014;28:749-56, 758.

2. Rindi G, Arnold R, Bosman FT, Capella C, Klimstra DS, Kloppel G, Komminoth P, Solcia E. Nomenclature and classification of neuroendocrine neoplasms of the digestive system. In WHO Classification of Tumours of the Digestive System, Eds. FT Bosman, F Carneiro, RH Hruban & N Theise. Lyon: IARC Press; 2010. pp. 13-14.

3. Sorbye H, Strosberg J, Baudin E, Klimstra DS, Yao JC. Gastroenteropancreatic high-grade neuroendocrine carcinoma. Cancer 2014;120:2814-23.

4. La Rosa S, Sessa F. High-grade poorly differentiated neuroendocrine carcinomas of the gastroenteropancreatic system: from morphology to proliferation and back. Endocr Pathol 2014;25:193-8.

5. Capdevila J, Salazar R, Halperin I, Abad A, Yao JC. Innovations therapy: mammalian target of rapamycin (mTOR) inhibitors for the treatment of neuroendocrine tumours. Cancer Metastasis Rev 2011;30:27-34.

6. Capdevila J, Tabernero J. A shining light in the darkness for the treatment of pancreatic neuroendocrine tumours. Cancer Discov 2011;1:213-21.

7. Hilfenhaus G, Gohrig A, Pape UF, Neumann T, Jann H, Zdunek D, Hess G, Stassen JM, Wiedenmann B, Detjen K, Pavel M, Fischer C. Placental growth factor supports neuroendocrine tumour growth and predicts disease prognosis in patients. Endocr Relat Cancer 2013;20:305-19.

8. Vallières E, Shepherd FA, Crowley J, Van Houtte P, Postmus PE, Carney D, Chansky K, Shaikh Z, Goldstraw P; International Association for the Study of Lung Cancer International Staging Committee and Participating Institutions. The IASLC Lung Cancer Staging Project: proposals regarding the relevance of TNM in the pathologic staging of small cell lung cancer in the forthcoming (seventh) edition of the TNM classification for lung cancer. J Thorac Oncol 2009;4:1049-59.

9. Faggiano A, Sabourin JC, Ducreux M, Lumbroso J, Duvillard P, Leboulleux S, Dromain C, Colao A, Schlumberger M, Baudin E. Pulmonary and extrapulmonary poorly differentiated large cell neuroendocrine carcinomas: diagnostic and prognostic features. Cancer 2007;110:265-74.

10. Travis WD. Advances in neuroendocrine lung tumors. Ann Oncol 2010;21 Suppl 7:vii65-71.

11. Rekhtmann N. Neuroendocrine tumors of the lung: an update. Arch Pathol Lab Med 2010;134:1628-38.

12. Bertino EM, Confer PD, Colonna JE, Ross P, Otterson GA. Pulmonary neuroendocrine/carcinoid tumors. Cancer 2009;115:4434-41.

13. Valente M, Catena L, Milione M, Pusceddu S, Formisano B, Bajetta E. Common diagnostic challenges in the histopathologic diagnosis of neuroendocrine lung tumors: a case report. Case Rep Oncol 2010;3:202-7.

14. Oberg KE. The management of neuroendocrine tumours: current and future medical therapy options. Clin Oncol (R Coll Radiol) 2012;24:282-93.

15. Reubi JC. Peptide receptors as molecular targets for cancer diagnosis and therapy. Endocr Rev 2003;24:389-427.

16. Modlin IM, Pavel M, Kidd M, Gustafsson BI. Review article: somatostatin analogues in the treatment of gastroenteropancreatic neuroendocrine (carcinoid) tumours. Aliment Pharmacol Ther 2010;31:169-88.

17. Bruns C, Lewis I, Briner U, Meno-Tetang G, Weckbecker G. SOM230: a novel somatostatin peptidomimetic with broad somatotropin release inhibiting factor (SRIF) receptor binding and a unique antisecretory profile. Eur J Endocrinol 2002;146:707-16.

18. Patel YC. Somatostatin and its receptor family. Front Neuroendocrinol 1999;20:157-98.

19. Møller LN, Stidsen CE, Hartmann B, Holst JJ. Somatostatin receptors. Biochim Biophys Acta 2003;1616:1-84.

20. Ruszniewski P, Ducreux M, Charyvialle JA, Blumberg J, Cloarec D, Michel H, Raymond JM, Dupas JL, Gouerou H, Jian R, Genestin E, Bernades P, Rougier P. Treatment of the carcinoid syndrome with the long acting somatostatin analogue lanreotide: a prospective study in 39 patients. Gut 1996;39:279-83.

21. Yamada Y, Post SR, Wang K, Tager HS, Bell GI, Seino S. Cloning and functional characterization of a family of human and mouse somatostatin receptors expressed in brain, gastrointestinal tract, and kidney. Proc Natl Acad Sci U S A 1992;89:251-5.

22. Yamada Y, Reisine T, Law SF, Ihara Y, Kubota A, Kagimoto S, Seino M, Seino Y, Bell GI, Seino S. Somatostatin receptors, an expanding gene family: cloning and functional characterization of human SSTR3, a protein coupled to adenylate cyclase. Mol Endocrinol 1992;6:2136-42.

23. Ben-Shlomo A, Zhou C, Pichurin O, Chesnokova V, Liu NA, Culler MD, Melmed S. Constitutive somatostatin receptor activity determines tonic pituitary cell response. Mol Endocrinol 2009;23:337-48.

24. Cescato R, Loesch KA, Waser B, Mäcke HR, Rivier JE, Reubi JC, Schonbrunn A. Agonist-biased signalling at the sst2A receptor: the multi-somatostatin analogs KE108 and SOM230 activate and antagonize distinct signalling pathways. Mol Endocrinol 2010;24:240-9.

25. Reubi JC, Eisenwiener KP, Rink H, Waser B, Mäcke HR. A new peptidic somatostatin agonist with high affinity to all five somatostatin receptors. Eur J Pharmacol 2002;456:45-9.

26. Schonbrunn A. Selective agonism in somatostatin receptor signalling and regulation. Mol Cell Endocrinol 2008;286:35-9.

27. Ferone D, Arvigo M, Semino C, Jaquet P, Saveanu A, Taylor JE, Moreau JP, Culler MD, Albertelli M, Minuto F, Barreca A. Somatostatin and dopamine receptor expression in lung carcinoma cells and effects of chimeric somatostatin-dopamine molecules on cell proliferation. Am J Physiol Endocrinol Metab 2005;289:E1044-50.

28. Arnold R, Trautmann ME, Creutzfeldt W, Benning R, Benning M, Neuhaus C, Jürgensen R, Stein K, Schäfer H, Bruns C, Dennler HJ. Somatostatin analogue octreotide and inhibition of tumour growth in metastatic endocrine gastroenteropancreatic tumours. Gut 1996;38:430-8.

29. De Sà SV, Corrêa-Giannella ML, Machado MC, de Souza JJ, Pereira MA, Patzina RA, Siqueira SA, Machado MC, Giannella-Neto D. Somatostatin receptors subtype 5 (SSTR5) mRNA expression is related to histopatological features of cell proliferation in insulinomas. Endocr Relat Cancer 2006;13:69-78.

30. Schmid HA, Lambertini C, van Vugt HH, Barzaghi-Rinaudo P, Schafer J, Hillenbrand R, Sailer AW, Kaufmann M, Nuciforo P. Monoclonal antibodies against the human somatostatin receptor subtypes 1-5: development and immunohistochemical application in neuroendocrine tumours. Neuroendocrinology 2012;95:232-47.

31. Reubi JC, Laissue J, Krenning E, Lamberts SW. Somatostatin receptors in human cancer: incidence, characteristics, functional correlates and clinical implications. J Steroid Biochem Mol Biol 1992;4:27-35.

32. Reubi JC. Peptide receptors as molecular targets for cancer diagnosis and therapy. Endocr Rev 2003;24:389-427.

33. Reubi JC, Waser B. Concomitant expression of several peptide receptors in neuroendocrine tumours: molecular basis for in vivo multireceptor tumour targeting. Eur J Nucl Med Mol Imaging 2003;30:781-93.

34. Reubi JC. Somatostatin and other Peptide receptors as tools for tumour diagnosis and treatment. Neuroendocrinology 2004;80 Suppl 1:51-6.

35. Reubi JC, Kappeler A, Wase B, Laissue J, Hipkin RW, Schonbrunn A. Immunoistochemical localisation of somatostatin receptros SST2A in human tumours. Am J Pathol 1998;153:233-45.

36. Papotti M, Bongiovanni M, Volante M, Allìa E, Landolfi S, Helboe L, Schindler M, Cole SL, Bussolati G. Expression of somatostatin receptros type 1-5 in 81 cases og gastrointestinal and pancreatic endocrine tumours. A correlative immunohistochemical and reverse-transcriptase polymerase chain reaction analysis. Virchovs Arch 2002;440:461-75.

37. Volante M, Rosas R, Allìa E, Granata R, Baragli A, Muccioli G, Papotti M. Somatostatin, cortistatin and their receptors in tumours. Mol Cell Endocrinol 2008;286:219-29.

38. Lahlou H, Guillermet J, Hortala M, Vernejoul F, Pyronnet S, Bousquet C, Susini C. Molecular signalling of somatostatin receptors. Ann N Y Acad Sci 2004;1014:121-31.

39. Reisine T, Bell GI. Molecular biology of somatostatin receptors. Endocr Rev 1995;16:427-42.

40. Lamberts SW, Krenning EP, Reubi JC. The role of somatostatin and its analogs in the diagnosis and treatment of tumours. Endocr Rev 1991;12:450-82.

41. Bousquet C, Puente E, Buscail L, Vaysse N, Susini C. Antiproliferative effect of somatostatin and analogs. Chemotherapy 2001;47 Suppl 2:30-9.

42. Butturini G, Bettini R, Missiaglia E, Mantovani W, Dalai I, Capelli P, Ferdeghini M, Pederzoli P, Scarpa A, Falconi M. Predictive factors of efficacy of the somatostatin analogue octreotide as first line therapy for advanced pancreatic endocrine carcinoma. Endocr Relat Cancer 2006;13:1213-21.

43. Schally AV. Oncological applications of somatostatin analogues. Cancer Res 1988;48:6977-85.

44. Weckbecker G, Raulf F, Stolz B, Bruns C. Somatostatin analogs for diagnosis and treatment of cancer. Pharmacol Ther 1993;60:245-64.

45. Pollak MN, Schally AV. Mechanisms of antineoplastic action of somatostatin analogs. Proc Soc Exp Biol Med 1998;217:143-52.

46. Froidevaux S, Eberle AN. Somatostatin analogs and radiopeptides in cancer therapy. Biopolymers 2002;66:161-83.

47. Schally AV, Nagy A. Chemotherapy targeted to cancers through tumoural hormone receptors. Trends Endocrinol Metab 2004;15:300-10.

48. Pyronnet S, Bousquet C, Najib S, Azar R, Laklai H, Susini C. Antitumour effects of somatostatin. Mol Cell Endocrinol 2008;286:230-7.

49. 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; PROMID Study Group. Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumour growth in patients with metastatic neuroendocrine midgut tumours: a report from the PROMID Study Group. J Clin Oncol 2009;27:4656-63.

50. Caplin ME, Pavel M, Ćwikla JB, Phan AT, Raderer M, Sedláčková E, Cadiot G, Wolin EM, Capdevila J, Wall L, Rindi G, Langley A, Martinez S, Blumberg J, Ruszniewski P; CLARINET Investigators. Lanreotide in metastatic enteropancreatic neuroendocrine tumours. N Engl J Med 2014;371:224-33.

51. Arnold R, Wittenberg M, Rinke A, Schade-Brittinger C, Aminossadati B, Ronicke Gress TM, Mueller HH; PROMID Study Group; Philipps University Marburg, Department of Internal Medicine, Division of Gastroenterology and Endocrinology, Marburg, Germany; KKS Marburg, Marburg, Germany; Philipps University Marburg; Deptartment of Gastroenterology, Marburg, Germany; Koordinierungszentrum für Klinische Studien der Philipps-Universität Marburg, Marburg, Germany; Institute of Medical Informatics, Biometry and Epidemiology, LMU Munich, München, Germany. PROMID Study Group. Placebo controlled, double blind, prospective, randomized study on the effect of octreotide LAR in the control of tumour growth in patients with metastatic neuroendocrine midgut tumours (PROMID): results on long-term survival. ASCO 2013;31:Abstr 4030.

52. Schmid HA. Pasireotide (SOM230): development, mechanism of action and potential applications. Mol Cell Endocrinol 2008;286:69-74.

53. Wolin EM, Jarzab B, Eriksson B, Walter T, Toumpanakis C, Morse MA, Tomassetti P, Weber MM, Fogelman DR, Ramage J, Poon D, Gadbaw B, Li J, Pasieka JL, Mahamat A, Swahn F, Newell-Price J, Mansoor W, Öberg K. A multicenter, randomized, blinded, phase III study of pasireotide LAR versus octreotide LAR in patients with metastatic neuroendocrine tumours (NET) with disease-related symptoms inadequately controlled by somatostatin analogs. J Clin Oncol 2013;31:abstr s4031.

54. Kulke MH, O'Dorisio T, Phan A, Bergsland E, Law L, Banks P, Freiman J, Frazier K, Jackson J, Yao JC, Kvols L, Lapuerta P, Zambrowicz B, Fleming D, Sands A. Telotristat etiprate, a novel serotonin synthesis inhibitor, in patients with carcinoid syndrome and diarrhea not adequately controlled by octreotide. Endocr Relat Cancer 2014;21:705-14.

55. Pavel M, Hörsch D, Caplin M, Ramage J, Seufferlein T, Valle J, Banks P, Lapuerta P, Sands A, Zambrowicz B, Fleming D, Wiedenmann B. Telotristat etiprate for carcinoid syndrome: a single-arm, multicenter trial. J Clin Endocrinol Metab 2015;100:1511-9.

56. Aparicio T, Ducreux M, Baudin E, Sabourin JC, De Baere T, Mitry E, Schlumberger M, Rougier P. Antitumour activity of somatostatin analogues in progressive metastatic neuroendocrine tumours. Eur J Cancer 2001;37:1014-9.

57. Filosso PL, Ruffini E, Oliaro A, Papalia E, Donati G, Rena O. Long-term survival of atypical bronchial carcinoids with liver metastases, treated with octreotide. Eur J Cardiothorac Surg 2002;21:913-7.

58. Hay N. The Akt-mTOR tango and its relevance to cancer. Cancer Cell 2005;8:179-83.

59. Alonso-Gordoa T, Capdevila J, Grande E. GEP-NETs Update: Biotherapy for neuroendocrine tumours. Eur J Endocrinol 2015;172:R31-46.

60. Jiao Y, Shi C, Edil BH, de Wilde RF, Klimstra DS, Maitra A, Schulick RD, Tang LH, Wolfgang CL, Choti MA, Velculescu VE, Diaz LA Jr, Vogelstein B, Kinzler KW, Hruban RH, Papadopoulos N. DAXX/ATRX, MEN1, and mTOR pathway genes are frequently altered in pancreatic neuroendocrine tumours. Science 2011;331:1199-203.

61. 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. Pancreatic endocrine tumours: expression profiling evidences a role for AKT-mTOR pathway. J Clin Oncol 2010;28:245-55.

62. Humar R, Kiefer FN, Berns H, Resink TJ, Battegay EJ. Hypoxia enhances vascular cell proliferation and angiogenesis in vitro via rapamycin (mTOR)-dependent signalling. FASEB J 2002;16:771-80.

63. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011;144:646-74.

64. 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. Daily oral everolimus activity in patients with metastatic pancreatic neuroendocrine tumours after failure of cytotoxic chemotherapy: a phase II trial. J Clin Oncol 2010;28:69-76.

65. 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; RAD001 in Advanced Neuroendocrine Tumors, Third Trial (RADIANT-3) Study Group. Everolimus for advanced pancreatic neuroendocrine tumours. N Engl J Med 2011;364:514-23.

66. Pavel ME, Hainsworth JD, Baudin E, Peeters M, Hörsch D, Winkler RE, Klimovsky J, Lebwohl D, Jehl V, Wolin EM, Oberg K, Van Cutsem E, Yao JC; RADIANT-2 Study Group. Everolimus plus octreotide long-acting repeatable for the treatment of advanced neuroendocrine tumours associated with carcinoid syndrome (RADIANT- 2): a randomised, placebo-controlled, phase 3 study. Lancet 2011;378:2005-12.

67. Fazio N, Granberg D, Grossman A, Saletan S, Klimovsky J, Panneerselvam A, Wolin EM. Everolimus plus octreotide long-acting repeatable in patients with advanced lung neuroendocrine tumors: analysis of the phase 3, randomized, placebo-controlled RADIANT-2 study. Chest 2013;143:955-62.

68. Duran I, Kortmansky J, Singh D, Hirte H, Kocha W, Goss G, Le L, Oza A, Nicklee T, Ho J, Birle D, Pond GR, Arboine D, Dancey J, Aviel-Ronen S, Tsao MS, Hedley D, Siu LL. A phase II clinical and pharmacodynamic study of temsirolimus in advanced neuroendocrine carcinomas. Br J Cancer 2006;95:1148-54.

69. Hafsi S, Pezzino FM, Candido S, Ligresti G, Spandidos DA, Soua Z, McCubrey JA, Travali S, Libra M. Gene alterations in the PI3K/PTEN/AKT pathway as a mechanism of drug-resistance (review). Int J Oncol 2012;40:639-44.

70. Zhang S, Yu D. PI(3)king apart PTEN's role in cancer. Clin Cancer Res 2010;16:4325-30.

71. Ramaswamy S, Nakamura N, Vazquez F, Batt DB, Perera S, Roberts TM, Sellers WR. Regulation of G1 progression by the PTEN tumour suppressor protein is linked to inhibition of the phosphatidylinositol 3-kinase/Akt pathway. Proc Natl Acad Sci U S A 1999;96:2110-5.

72. Myers MP, Pass I, Batty IH, Van der Kaay J, Stolarov JP, Hemmings BA, Wigler MH, Downes CP, Tonks NK. The lipid phosphatase activity of PTEN is critical for its tumour suppressor function. Proc Natl Acad Sci U S A 1998;95:13513-8.

73. Furnari FB, Huang HJ, Cavenee WK. The phosphoinositol phosphatase activity of PTEN mediates a serum-sensitive G1 growth arrest in glioma cells. Cancer Res 1998;58:5002-8.

74. Putz U, Howitt J, Doan A, Goh CP, Low LH, Silke J, Tan SS. The tumour suppressor PTEN is exported in exosomes and has phosphatase activity in recipient cells. Sci Signal 2012;5:ra70.

75. Tamura M, Gu J, Takino T, Yamada KM. Tumour suppressor PTEN inhibition of cell invasion, migration, and growth: differential involvement of focal adhesion kinase and p130Cas. Cancer Res 1999;59:442-9.

76. Kim JS, Xu X, Li H, Solomon D, Lane WS, Jin T, Waldman T. Mechanistic analysis of a DNA damage-induced, PTEN-dependent size checkpoint in human cells. Mol Cell Biol 2011;31:2756-71.

77. Wang L, Ignat A, Axiotis CA. Differential expression of the PTEN tumour suppressor protein in fetal and adult neuroendocrine tissues and tumours: progressive loss of PTEN expression in poorly differentiated neuroendocrine neoplasms. Appl Immunohistochem Mol Morphol 2002;10:139-46.

78. Collaud S, Tischler V, Atanassoff A, Wiedl T, Komminoth P, Oehlschlegel C, Weder W, Soltermann A. Lung neuroendocrine tumors: correlation of ubiquitinylation 1 and sumoylation with nucleo-cytosolic partitioning of PTEN. BMC Cancer 2015;15:74.

79. Samani AA, Yakar S, LeRoith D, Brodt P. The role of the IGF system in cancer growth and metastasis: overview and recent insights. Endocr Rev 2007;28:20-47.

80. Furukawa M, Raffeld M, Mateo C, Sakamoto A, Moody TW, Ito T, Venzon DJ, Serrano J, Jensen RT. Increased expression of insulin-like growth factor I and/or its receptor in gastrinomas is associated with low curability, increased growth, and development of metastases. Clin Cancer Res 2005;11:3233-42.

81. Chaves J, Saif MW. IGF system in cancer: from bench to clinic. Anticancer Drugs 2011;22:206-12.

82. von Wichert G, Jehle PM, Hoeflich A, Koschnick S, Dralle H, Wolf E, Wiedenmann B, Boehm BO, Adler G, Seufferlein T. Insulin-like growth factor-I is an autocrine regulator of chromogranin A secretion and growth in human neuroendocrine tumor cells. Cancer Res 2000;60:4573-81.

83. Nilsson O, Wangberg B, Theodorsson E, Skottner A, Ahlman H. Presence of IGF-I in human midgut carcinoid tumours--an autocrine regulator of carcinoid tumour growth? Int J Cancer 1992;51:195-203.

84. Nilsson O, Wangberg B, McRae A, Dahlstrom A, Ahlman H. Growth factors and carcinoid tumours. Acta Oncol 1993;32:115-24.

85. Wulbrand U, Wied M, Zöfel P, Göke B, Arnold R, Fehmann H. Growth factor receptor expression in human gastroenteropancreatic neuroendocrine tumours. Eur J Clin Invest 1998;28:1038-49.

86. Höpfner M, Baradari V, Huether A, Schöfl C, Scherübl H. The insulin-like growth factor receptor 1 is a promising target for novel treatment approaches in neuroendocrine gastrointestinal tumours. Endocr Relat Cancer 2006;13:135-49.

87. Vitale L, Lenzi L, Huntsman SA, Canaider S, Frabetti F, Casadei R, Facchin F, Carinci P, Zannotti M, Coppola D, Strippoli P. Differential expression of alternatively spliced mRNA forms of the insulin-like growth factor 1 receptor in human neuroendocrine tumours. Oncol Rep 2006;15:1249-56.

88. Richardson PG, Mitsiades CS, Laubach JP, Lonial S, Chanan-Khan AA, Anderson KC. Inhibition of heat shock protein 90 (HSP90) as a therapeutic strategy for the treatment of myeloma and other cancers. Br J Haematol 2011;152:367-79.

89. Gloesenkamp C, Nitzsche B, Lim AR, Normant E, Vosburgh E, Schrader M, Ocker M, Scherübl H, Höpfner M. Heat shock protein 90 is a promising target for effective growth inhibition of gastrointestinal neuroendocrine tumours. Int J Oncol 2012;40:1659-67.

90. Gilbert JA, Adhikari LJ, Lloyd RV, Halfdanarson TR, Muders MH, Ames MM. Molecular markers for novel therapeutic strategies in pancreatic endocrine tumors. Pancreas 2013;42:411-21.

91. Froesch ER, Schmid C, Schwander J, Zapf J. Actions of insulin-like growth factors. Ann Rev Physiol 1985;47:443-67.

92. Schoenle E, Zapf J, Humbel RE, Froesch ER. Insulin-like growth factor I stimulates growth of hypophysectomised rats. Nature 1982;296:252-3.

93. Adams SO, Nissley SP, Handwerger S, Rechler MM. Developmental patterns of insulin-like growth factor-I and -II synthesis and regulation in rat fibroblasts. Nature 1983;302:150-3.

94. Shi Y, Yan H, Frost P, Gera J, Lichtenstein A. 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 2005;4:1533-40.

95. Wan X, Harkavy B, Shen N, Grohar P, Helman LJ. Rapamycin induces feedback activation of Akt signaling through an IGF-1R-dependent mechanism. Oncogene 2007;26:1932-40.

96. 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. mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt. Cancer Res 2006;66:1500-8.

97. Rowinsky EK, Youssoufian H, Tonra JR, Solomon P, Burtrum D, Ludwig DL. IMC-A12, a human IgG1 monoclonal antibody to the insulin-like growth factor I receptor. Clin Cancer Res 2007;13:5549-55s.

98. Anthony LB, Loehrer PJ, Leong S, Shah MH, Safran H, Senzer NN, Zojwalla NJ, Youssoufian H. Phase II study of cixutumumab (IMC-A12) plus depot octreotide for patients with metastatic carcinoid or islet cell carcinoma. J Clin Oncol 2010;28;15s .

99. Naing A, Kurzrock R, Burger A, Gupta S, Lei X, Busaidy N, Hong D, Chen HX, Doyle LA, Heilbrun LK, Rohren E, Ng C, Chandhasin C, LoRusso P. Phase I Trial of Cixutumumab Combined with Temsirolimus in Patients with Advanced Cancer. Clin Cancer Res 2011;17:6052-60.

100. Rothenberg ML, Tolcher AW, Sarantopoulos J, Rodon J, Friberg G, Deng H, McCafferey I, Hwang Y, Puzanov I. AMG 479 monotherapy to treat patients with advanced GI carcinoid tumors: a subset analysis from the first-in-human study. Presented at the ASCO Gastrointestinal Cancers Symposium, San Francisco, January 2009.

101. Strosberg JR, Chan JA, Ryan DP, Meyerhardt JA, Fuchs CS, Abrams T, Regan E, Brady R, Weber J, Campos T, Kvols LK, Kulke MH. A multi-institutional, phase II open-label study of ganitumab (AMG 479) in advanced carcinoid and pancreatic neuroendocrine tumors. Endocr Relat Cancer 2013;20:383-90.

102. Sartelet H, Decaussin M, Devouassoux G. Nawrocki-Raby B, Brichon PY, Brambilla C, Brambilla E. Expression of vascular endothelial growth factor (VEGF) and its receptors (VEGF-R1 [Flt-1] and VEGF-R2 [KDR/Flk-1]) in tumor lets and in neuroendocrine cell hyperplasia of the lung. Hum Pathol 2004;35:1210-7.

103. Bertino EM, Confer PD, Colonna JE, Ross P, Otterson GA. Pulmonary neuroendocrine/carcinoid tumors. Cancer 2009;115:4434-41.

104. Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med 1995;1:27-31.

105. Berger DP, Herbstritt L, Dengler WA, Marmé D, Mertelsmann R, Fiebig HH. Vascular endothelial growth factor (VEGF) mRNA expression in human tumour models of different histologies. Ann Oncol 1995;6:817-25.

106. Lawnicka H, Stepieñ H, Wyczółkowska J, Kolago B, Kunert-Radek J, Komorowski J. Effect of somatostatin and octreotide on proliferation and vascular endothelial growth factor secretion from murine endothelial cell line (HECa10) culture. Biochem Biophys Res Commun 2000;268:567-71.

107. Kuo CJ, Farnebo F, Yu EY, Christofferson R, Swearingen RA, Carter R, von Recum HA, Yuan J, Kamihara J, Flynn E, D'Amato R, Folkman J, Mulligan RC. Comparative evaluation of the antitumour activity of antiangiogenic proteins delivered by gene transfer. Proc Natl Acad Sci U S A 2001;98:4605-10.

108. Matsumoto T, Claesson-Welsh L. VEGF receptor signal transduction. Sci STKE 2001;2001:re21.

109. Klagsbrun M, Takashima S, Mamluk R. The role of neuropilin in vascular and tumour biology. Adv Exp Med Biol 2002;515:33-48.

110. Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med 2003;9:669-76.

111. Treiber G, Wex T, Röcken C, Fostitsch P, Malfertheiner P. Impact of biomarkers on disease survival and progression in patients treated with octreotide for advanced hepatocellular carcinoma. J Cancer Res Clin Oncol 2006;132:699-708.

112. Dimitroulopoulos D, Xinopoulos D, Tsamakidis K, Zisimopoulos A, Andriotis E, Panagiotakos D, Fotopoulou A, Chrysohoou C, Bazinis A, Daskalopoulou D, Paraskevas E. Long acting octreotide in the treatment of advanced hepatocellular cancer and overexpression of somatostatin receptors: randomized placebo-controlled trial. World J Gastroenterol 2007;13:3164-70.

113. Ho QT, Kuo CJ. Vascular endothelial growth factor: Biology and therapeutic applications. Int J Biochem Cell Biol 2007;39:1349-57.

114. O'Farrell AM, Abrams TJ, Yuen HA, Ngai TJ, Louie SG, Yee KW, Wong LM, Hong W, Lee LB, Town A, Smolich BD, Manning WC, Murray LJ, Heinrich MC, Cherrington JM. SU11248 is a novel FLT3 tyrosine kinase inhibitor with potent activity in vitro and in vivo. Blood 2003;101:3597-605.

115. Faivre S, Delbaldo C, Vera K, Robert C, Lozahic S, Lassau N, Bello C, Deprimo S, Brega N, Massimini G, Armand JP, Scigalla P, Raymond E. Safety, pharmacokinetic, and antitumor activity of SU11248, a novel oral multitarget tyrosine kinase inhibitor, in patients with cancer. J Clin Oncol 2006;24:25-35.

116. Kulke MH, Lenz HJ, Meropol NJ, Posey J, Ryan DP, Picus J, Bergsland E, Stuart K, Tye L, Huang X, Li JZ, Baum CM, Fuchs CS. Activity of sunitinib in patients with advanced neuroendocrine tumours. J Clin Oncol 2008;26:3403-10.

117. Raymond E, Dahan L, Raoul JL, Bang YJ, Borbath I, Lombard-Bohas C, Valle J, Metrakos P, Smith D, Vinik A, Chen JS, Hörsch D, Hammel P, Wiedenmann B, Van Cutsem E, Patyna S, Lu DR, Blanckmeister C, Chao R, Ruszniewski P. Sunitinib malate for the treatment of pancreatic neuroendocrine tumours. N Engl J Med 2011;364:501-13.

118. Yao JC, Phan AT, Hoff PM, Chen HX, Charnsangavej C, Yeung SC, Hess K, Ng C, Abbruzzese JL, Ajani JA. Targeting vascular endothelial growth factor in advanced carcinoid tumour: a random assignment phase II study of depot octreotide with bevacizumab and pegylated interferon alpha-2b. J Clin Oncol 2008;26:1316-23.

119. Faivre S, Sablin MP, Dreyer C, Raymond E. Novel anticancer agents in clinical trials for well-differentiated neuroendocrine tumours. Endocrinol Metab Clin North Am 2010;39:811-26.

120. Chan JA, Stuart K, Earle CC, Clark JW, Bhargava P, Miksad R, Blaszkowsky L, Enzinger PC, Meyerhardt JA, Zheng H, Fuchs CS, Kulke MH. Prospective Study of bevacizumab plus temozolomide in patients with advanced neuroendocrine tumors. J Clin Oncol 2012;l 30:2963-8.

121. Yao JC, Phan AT, Fogleman D, Ng CS, Jacobs CB, Dagohoy CD, Leary C, Hess KR. Randomized run-in study of bevacizumab (B) and everolimus (E) in low- to intermediate-grade neuroendocrine tumors (LGNETs) using perfusion CT as functional biomarker. J Clin Oncol 2010;28 suppl 15:abstr 4002.

122. Sonpavde G, Hutson TE. Pazopanib: a novel multitargeted tyrosine kinase inhibitor. Curr Oncol Rep 2007;9:115-9.

123. Ahn HK, Choi JY, Kim KM, Kim H, Choi SH, Park SH, Park JO, Lim HY, Kang WK, Lee J, Park YS. Phase II study of pazopanib monotherapy in metastatic gastroenteropancreatic neuroendocrine tumours. Br J Cancer 2013;109:1414-9.

124. Phan AT, Yao JC, Fogelman DR, Hess KR, Ng CS, Bullock SA, Malinowski P, Regan E, Kulke M. A prospective, multi-institutional phase II study of GW786034 (pazopanib) and depot octreotide (sandostatin LAR) in advanced low-grade neuroendocrine carcinoma (LGNEC). Proc Am Soc Clin Oncol 2010;28:abstr 4001.

125. Phan AT, Halperin DM, Chan JA, Hess KR, Malinowski P, Regan E, Ng CS, Yao JC, Kulke MH. Pazopanib and depot octreotide in advanced, well-differentiated neuroendocrine tumours: a multicentre, single-group, phase 2 study. Lancet Oncol 2015;16:695-703.

126. Wilhelm SM, Carter C, Tang L, Wilkie D, McNabola A, Rong H, Chen C, Zhang X, Vincent P, McHugh M, Cao Y, Shujath J, Gawlak S, Eveleigh D, Rowley B, Liu L, Adnane L, Lynch M, Auclair D, Taylor I, Gedrich R, Voznesensky A, Riedl B, Post LE, Bollag G, Trail PA. BAY 43-9006 exhibits broad spectrum oral antitumour activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumour progression and angiogenesis. Cancer Res 2004;64:7099-109.

127. Wilhelm SM, Dumas J, Adnane L, Lynch M, Carter CA, Schütz G, Thierauch KH, Zopf D. Regorafenib (BAY 73-4506): a new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumour activity. Int J Cancer 2011;129:245-55.

128. Bill R, Fagiani E, Zumsteg A, Antoniadis H, Johansson D, Haefliger S, Albrecht I, Hilberg F, Christofori G. Nintedanib Is a Highly Effective Therapeutic for Neuroendocrine Carcinoma of the Pancreas (PNET) in the Rip1Tag2 Transgenic Mouse Model. Clin Cancer Res 2015;21:4856-67.

129. Bago-Horvath Z, Sieghart W, Grusch M, Lackner A, Hayden H, Pirker C, Komina O, Węsierska-Gądek J, Haitel A, Filipits M, Berger W, Schmid K. Synergistic effects of erlotinib and everolimus on bronchial carcinoids and large-cell neuroendocrine carcinomas with activated EGFR/AKT/ mTOR pathway. Neuroendocrinology 2012;96:228-37.

130. Shah T, Hochhauser D, Frow R, Quaglia A, Dhillon AP, Caplin ME. Epidermal growth factor receptor expression and activation in neuroendocrine tumours. J Neuroendocrinol 2006;18:355-60.

131. Papouchado B, Erickson LA, Rohlinger AL, Hobday TJ, Erlichman C, Ames MM, Lloyd RV. Epidermal growth factor receptor and activated epidermal growth factor receptor expression in gastrointestinal carcinoids and pancreatic endocrine carcinomas. Mod Pathol 2005;18:1329-35.

132. Srivastava A, Alexander J, Lomakin I, Dayal Y. Immunohistochemical expression of transforming growth factor alpha and epidermal growth factor receptor in pancreatic endocrine tumours. Hum Pathol 2001;32:1184-9.

133. Nilsson O, Wangberg B, Kolby L, Schultz GS, Ahlman H. Expression of transforming growth factor alpha and its receptor in human neuroendocrine tumours. Int J Cancer 1995;60:645-51.

134. Krishnamurthy S, Dayal Y. Immunohistochemical expression of transforming growth factor alpha and epidermal growth factor receptor in gastrointestinal carcinoids. Am J Surg Pathol 1997;21:327-33.

135. Shimizu T, Tanaka S, Haruma K, Kitadai Y, Yoshihara M, Sumii K, Kajiyama G, Shimamoto F. Growth characteristics of rectal carcinoid tumours. Oncology 2000;59:229-37.

136. Hobday TJ, Holen K, Donehower RC, Camoriano J, Kim G, Picus J, Philip P, Lloyd R, Mahoney M, Erlichman C. A phase II trial of gefitinib in patients (pts) with progressive metastatic neuroendocrine tumours (NET): a phase II consortium (P2C) study. J Clin Oncol 2006; 24:189S. Available from:

137. Modlin IM, Shapiro MD, Kidd M. Carcinoid tumor and fibrosis: an association with no explanation. Am J Gastroenterol 2004;99:2466-78.

138. Yao JC, Zhang JX, Rashid A, Yeung SC, Szklaruk J, Hess K, Xie K, Ellis L, Abbruzzese JL, Ajani JA. Clinical and in vitro studies of imatinib in advanced carcinoid tumours. Clin Cancer Res 2007;13:234-40.

139. Lankat-Buttgereit B, Hörsch D, Barth P, Arnold R, Blöcker S, Göke R. Effects of the tyrosine kinase inhibitor imatinib on neuroendocrine tumour cell growth. Digestion 2005;71:131-40.

140. Schott M, Feldkamp J, Lettmann M, Simon D, Scherbaum WA, Seissler J. Dendritic cell immunotherapy in a neuroendocrine pancreas carcinoma. Clin Endocrinol (Oxf) 2001;55:271-7.

Journal of Cancer Metastasis and Treatment
ISSN 2454-2857 (Online) 2394-4722 (Print)


All published articles are preserved here permanently:


All published articles are preserved here permanently: