Cancer and Metastasis Reviews

, Volume 32, Issue 3–4, pp 465–477 | Cite as

The targeted therapy revolution in neuroendocrine tumors: in search of biomarkers for patient selection and response evaluation

  • Sara De Dosso
  • Enrique Grande
  • Jorge Barriuso
  • Daniel Castellano
  • Josep Tabernero
  • Jaume Capdevila


The molecular events of tumorigenesis in neuroendocrine tumors are poorly understood. Understanding of the molecular alterations will lead to the identification of molecular markers, providing new targets for therapeutics. The purpose of this review was to critically analyze the genetic abnormalities in neuroendocrine tumors, with the aim of identifying biomarkers that indicate a response to agents developed against these targets and to serve as an understanding for the combinations of different active compounds. Human epidermal growth factor receptor 1/2 (EGFR and HER2), vascular endothelial growth factor receptors, hepatocyte growth factor receptor (c-Met), platelet-derived growth factor receptor, insulin-like growth factor, phosphatidylinositol 3-kinase–Akt–mammalian target of rapamycin pathway, and heat shock proteins are all interesting candidate biomarkers with involvement in carcinogenesis and tumor evolution of several neoplasms, including neuroendocrine tumors. Some of them have already been evaluated both as targets and also as biomarkers in clinical trials conducted in advanced neuroendocrine tumor settings, and others should encourage further investigations into innovative therapeutic opportunities.


Neuroendocrine tumor Biomarker Target therapy Tyrosine kinase inhibitor 


  1. 1.
    Yao, J. C., Hassan, M., Phan, A., Dagohoy, C., Leary, C., Mares, J. E., Abdalla, E. K., et al. (2008). One hundred years after “carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. Journal of Clinical Oncology, 26, 3063–3072.PubMedCrossRefGoogle Scholar
  2. 2.
    Modlin, I. M., Lye, K. D., & Kidd, M. (2003). A 5-decade analysis of 13715 carcinoid tumors. Cancer, 97, 934–959.PubMedCrossRefGoogle Scholar
  3. 3.
    DeLellis, R. A. (2001). The neuroendocrine system and its tumors. American Journal of Clinical Pathology, 115, S5.PubMedGoogle Scholar
  4. 4.
    Grande, E., Capdevila, J., Barriuso, J., Anton-Aparicio, J., & Castellano, D. (2012). Gastroenteropancreatic neuroendocrine tumor cancer stem cells: do they exist? Cancer Metastasis Reviews, 31(1-2), 47–53.PubMedCrossRefGoogle Scholar
  5. 5.
    Castellano, D., Salazar, R., & Raymond, E. (2011). Future perspectives on neuroendocrine tumors. Cancer Metastasis Reviews, 30(Suppl 1), 35–40.PubMedGoogle Scholar
  6. 6.
    Grozinsky-Glasberg, S., Shimon, I., & Rubinfeld, H. (2012). The role of cell lines in the study of neuroendocrine tumors. Neuroendocrinology, 96, 173–187.PubMedCrossRefGoogle Scholar
  7. 7.
    Arany, I., Rady, P., Evers, B. M., Tyring, S. K., & Townsend, C. M. (1994). Analysis of multiple molecular changes in human endocrine tumors. Surgical Oncology, 3(3), 153–159.PubMedCrossRefGoogle Scholar
  8. 8.
    Zitzmann, K., De Toni, E. N., Brand, S., Göke, B., Meinecke, J., Spöttl, G., et al. (2007). The novel mTOR inhibitor RAD001 (everolimus) induces antiproliferative effects in human pancreatic neuroendocrine tumor cells. Neuroendocrinology, 85(1), 54–60.PubMedCrossRefGoogle Scholar
  9. 9.
    Pitt, S. C., Chen, H., & Kunnimalaiyaan, M. (2009). Inhibition of phosphatidylinositol 3-kinase/Akt signaling suppresses tumor cell proliferation and neuroendocrine marker expression in GI carcinoid tumors. Annals of Surgical Oncology, 16(10), 2936–2942.PubMedCrossRefGoogle Scholar
  10. 10.
    Kölby, L., Bernhardt, P., Ahlman, H., Wängberg, B., Johanson, V., Wigander, A., et al. (2001). A transplantable human carcinoid as model for somatostatin receptor-mediated and amine transporter-mediated radionuclide uptake. American Journal of Pathology, 158(2), 745–755.PubMedCrossRefGoogle Scholar
  11. 11.
    Zitzmann, K., Rüden, J., Brand, S., Göke, B., Lichtl, J., Spöttl, G., & Auernhammer, C. J. (2010). Compensatory activation of Akt in response to mTOR and Raf inhibitors—a rationale for dual-targeted therapy approaches in neuroendocrine tumor disease. Cancer Letter, 295(1), 100–109.CrossRefGoogle Scholar
  12. 12.
    Hanahan, D. (1985). Heritable formation of pancreatic beta-cell tumors in trasngenic mice expressing recombinant insulin/simian virus 40 oncogenes. Nature, 315, 115–122.PubMedCrossRefGoogle Scholar
  13. 13.
    Bergers, G., Song, S., Meyer-Morse, N., Bergsland, E., & Hanahan, D. (2003). Benefits of targeting both pericytes and endothelial cells in the tumor vasculature with kinase inhibitors. Journal of Clinical Investigation, 111(9), 1287–1295.PubMedGoogle Scholar
  14. 14.
    Kitadai, Y., Sasaki, T., Nakamura, T., Bucana, C. D., & Fidler, I. J. (2006). Targeting the expression of platelet-derived growth factor receptor by reactive stroma inhibits growth ad metastasis of human colon carcinoma. American Journal of Pathology, 169, 2054–2065.PubMedCrossRefGoogle Scholar
  15. 15.
    Kaplan, C. D., Kruger, J. A., Zhou, H., Luo, Y., Xiang, R., & Reisteld, R. A. (2006). A novel DNA vaccine encoding PDGFRbeta suppresses growth and dissemination of murine colon, lung and breast carcinoma. Vaccine, 24, 6994–7002.PubMedCrossRefGoogle Scholar
  16. 16.
    Chiu, C. W., Nozawa, H., & Hanahan, D. (2010). Survival benefit with proapoptotic molecular and pathologic responses from dual targeting of mammalian target of rapamycin and epidermal growth factor receptor in a preclinical model of pancreatic neuroendocrine carcinogenesis. Journal of Clinical Oncology, 28(29), 4425–4433.PubMedCrossRefGoogle Scholar
  17. 17.
    Rinke, A., Müller, H. H., Schade-Brittinger, C., Klose, K. J., Barth, P., Wied, M., et al. (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. Journal of Clinical Oncology, 27(28), 4656–4663.PubMedCrossRefGoogle Scholar
  18. 18.
    Yao, J. C., Shah, M. H., Ito, T., Bohas, C. L., Wolin, E. M., Van Cutsem, E., et al. (2011). Everolimus for advanced pancreatic neuroendocrine tumors. The New England Journal of Medicine, 364(6), 514–523.PubMedCrossRefGoogle Scholar
  19. 19.
    Raymond, E., Dahan, L., Raoul, J. L., Bang, Y. J., Borbath, I., Lombard-Bohas, C., et al. (2011). Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. The New England Journal of Medicine, 364(6), 501–513.PubMedCrossRefGoogle Scholar
  20. 20.
    Naraev, B., Strosberg, J. R., & Halfdanarson, T. R. (2012). Current status and perspectives of targeted therapy in well differentiated neuroendocrine tumors. Oncology, 83, 117–127.PubMedCrossRefGoogle Scholar
  21. 21.
    Kulke, M. H., Hornick, J. L., Frauenhoffer, C., Hooshmand, S., Ryan, D. P., Enzinger, P. C., et al. (2009). O 6-methylguanine DNA methyltransferase deficiency and response to temozolomide-based therapy in patients with neuroendocrine tumors. Clinical Cancer Research, 15(1), 338–345.PubMedCrossRefGoogle Scholar
  22. 22.
    Shah, T., Hochhauser, D., Frow, R., Quaglia, A., Dhillon, A. P., & Caplin, M. E. (2006). Epidermal growth factor receptor expression and activation in neuroendocrine tumours. Journal of Neuroendocrinology, 18(5), 355–360.PubMedCrossRefGoogle Scholar
  23. 23.
    Srivastava, A., Alexander, J., Lomakin, I., & Dayal, Y. (2001). Immunohistochemical expression of transforming growth factor alpha and epidermal growth factor receptor in pancreatic endocrine tumors. Human Pathology, 32(11), 1184–1189.PubMedCrossRefGoogle Scholar
  24. 24.
    Gilbert, J. A., Adhikari, L. J., Lloyd, R. V., Rubin, J., Haluska, P., Carboni, J. M., et al. (2010). Molecular markers for novel therapies in neuroendocrine (carcinoid) tumors. Endocrine-Related Cancer, 17(3), 623–636.PubMedCrossRefGoogle Scholar
  25. 25.
    Rickman, O. B., Vohra, P. K., Sanyal, B., Vrana, J. A., Aubry, M. C., Wigle, D. A., et al. (2009). Analysis of ErbB receptors in pulmonary carcinoid tumors. Clinical Cancer Research, 15(10), 3315–3324.PubMedCrossRefGoogle Scholar
  26. 26.
    Tannapfel, A., Vomschloss, S., Karhoff, D., Markwarth, A., Hengge, U. R., Wittekind, C., et al. (2005). BRAF gene mutations are rare events in gastroenteropancreatic neuroendocrine tumors. American Journal of Clinical Pathology, 123(2), 256–260.PubMedCrossRefGoogle Scholar
  27. 27.
    Hobday, T. J., Holen, K., Donehower, R., Camoriano, J., Kim, G., Picus, J., et al. (2006). A phase II trial of gefitinib in patients (pts) with progressive metastatic neuroendocrine tumors (NET): a Phase II Consortium (P2C) study. ASCO Meeting Abstracts, 24(18), 4043.Google Scholar
  28. 28.
    Azzoni, C., Bottarelli, L., Cecchini, S., Lagrasta, C., Pizzi, S., D’Adda, T., et al. (2011). Involvement of HER-2/neu and metastasis-related proteins in the development of ileal neuroendocrine tumors. Virchows Archiv, 458(5), 525–536.PubMedCrossRefGoogle Scholar
  29. 29.
    Hansel, D. E., Rahman, A., House, M., Ashfaq, R., Berg, K., Yeo, C. J., et al. (2004). Met proto-oncogene and insulin-like growth factor binding protein 3 overexpression correlates with metastatic ability in well-differentiated pancreatic endocrine neoplasms. Clinical Cancer Research, 10(18 Pt 1), 6152–6158.PubMedCrossRefGoogle Scholar
  30. 30.
    Peghini, P. L., Iwamoto, M., Raffeld, M., Chen, Y. J., Goebel, S. U., Serrano, J., et al. (2002). Overexpression of epidermal growth factor and hepatocyte growth factor receptors in a proportion of gastrinomas correlates with aggressive growth and lower curability. Clinical Cancer Research, 8(7), 2273–2285.PubMedGoogle Scholar
  31. 31.
    Sennino, B., Ishiguro-Oonuma, T., Wei, Y., Naylor, R. M., Williamson, C. W., Bhagwandin, V., et al. (2012). Suppression of tumor invasion and metastasis by concurrent inhibition of c-Met and VEGF signaling in pancreatic neuroendocrine tumors. Cancer Discovery, 2(3), 270–287.PubMedCrossRefGoogle Scholar
  32. 32.
    Wulbrand, U., Remmert, G., Zofel, P., Wied, M., Arnold, R., & Fehmann, H. C. (2000). mRNA expression patterns of insulin-like growth factor system components in human neuroendocrine tumours. European Journal of Clinical Investigation, 30(8), 729–739.PubMedCrossRefGoogle Scholar
  33. 33.
    Hopfner, M., Baradari, V., Huether, A., Schofl, C., & Scherubl, H. (2006). The insulin-like growth factor receptor 1 is a promising target for novel treatment approaches in neuroendocrine gastrointestinal tumours. Endocrine-Related Cancer, 13(1), 135–149.PubMedCrossRefGoogle Scholar
  34. 34.
    Tolcher, A. W., Sarantopoulos, J., Patnaik, A., Papadopoulos, K., Lin, C. C., Rodon, J., et al. (2009). Phase I, pharmacokinetic, and pharmacodynamic study of AMG 479, a fully human monoclonal antibody to insulin-like growth factor receptor 1. Journal of Clinical Oncology, 27(34), 5800–5807.PubMedCrossRefGoogle Scholar
  35. 35.
    Fjallskog, M. L., Lejonklou, M. H., Oberg, K. E., Eriksson, B. K., & Janson, E. T. (2003). Expression of molecular targets for tyrosine kinase receptor antagonists in malignant endocrine pancreatic tumors. Clinical Cancer Research, 9(4), 1469–1473.PubMedGoogle Scholar
  36. 36.
    Corbo, V., Beghelli, S., Bersani, S., Antonello, D., Talamini, G., Brunelli, M., et al. (2012). Pancreatic endocrine tumours: mutational and immunohistochemical survey of protein kinases reveals alterations in targetable kinases in cancer cell lines and rare primaries. Annals of Oncology, 23(1), 127–134.PubMedCrossRefGoogle Scholar
  37. 37.
    Bukowski, R. M., Eisen, T., Szczylik, C., Stadler, W. M., Simantov, R., Shan, M., et al. (2007). Final results of the randomized phase III trial of sorafenib in advanced renal cell carcinoma: survival and biomarker analysis. ASCO Meeting Abstracts, 25(18), 5023.Google Scholar
  38. 38.
    Mass, R. D., Sarkar, S., Holden, S. N., & Hurwitz, H. (2005). Clinical benefit from bevacizumab (BV) in responding (R) and non-responding (NR) patients (pts) with metastatic colorectal cancer (mCRC). ASCO Meeting Abstracts, 23(16), 3514.Google Scholar
  39. 39.
    Terris, B., Scoazec, J. Y., Rubbia, L., Bregeaud, L., Pepper, M. S., Ruszniewski, P., et al. (1998). Expression of vascular endothelial growth factor in digestive neuroendocrine tumours. Histopathology, 32(2), 133–138.PubMedCrossRefGoogle Scholar
  40. 40.
    La Rosa, S., Uccella, S., Finzi, G., Albarello, L., Sessa, F., & Capella, C. (2003). Localization of vascular endothelial growth factor and its receptors in digestive endocrine tumors: correlation with microvessel density and clinicopathologic features. Human Pathology, 34(1), 18–27.PubMedCrossRefGoogle Scholar
  41. 41.
    Oxboel, J., Binderup, T., Knigge, U., & Kjaer, A. (2009). Quantitative gene-expression of the tumor angiogenesis markers vascular endothelial growth factor, integrin alphaV and integrin beta3 in human neuroendocrine tumors. Oncology Reports, 21(3), 769–775.PubMedGoogle Scholar
  42. 42.
    Kulke, M. H., Lenz, H. J., Meropol, N. J., Posey, J., Ryan, D. P., Picus, J., et al. (2008). Activity of sunitinib in patients with advanced neuroendocrine tumors. Journal of Clinical Oncology, 26(20), 3403–3410.PubMedCrossRefGoogle Scholar
  43. 43.
    Bello, C., Deprimo, S. E., Friece, C., Smeraglia, J., Sherman, L., Tye, L., et al. (2006). Analysis of circulating biomarkers of sunitinib malate in patients with unresectable neuroendocrine tumors (NET): VEGF, IL-8, and soluble VEGF receptors 2 and 3. ASCO Meeting Abstracts, 24(18), 4045.Google Scholar
  44. 44.
    Garcia-Donas, J., Esteban, E., Leandro-Garcia, L. J., Castellano, D. E., del Alba, A. G., Climent, M. A., et al. (2011). Single nucleotide polymorphism associations with response and toxic effects in patients with advanced renal-cell carcinoma treated with first-line sunitinib: a multicentre, observational, prospective study. The Lancet Oncology, 12(12), 1143–1150.PubMedCrossRefGoogle Scholar
  45. 45.
    Yao, J. C. (2007). Neuroendocrine tumors. Molecular targeted therapy for carcinoid and islet-cell carcinoma. Best Practice & Research. Clinical Endocrinology & Metabolism, 21(1), 163–172.CrossRefGoogle Scholar
  46. 46.
    Missiaglia, E., Dalai, I., Barbi, S., Beghelli, S., Falconi, M., della Peruta, M., et al. (2010). Pancreatic endocrine tumors: expression profiling evidences a role for AKT–mTOR pathway. Journal of Clinical Oncology, 28(2), 245–255.PubMedCrossRefGoogle Scholar
  47. 47.
    Corbo, V., Dalai, I., Scardoni, M., Barbi, S., Beghelli, S., Bersani, S., et al. (2010). MEN1 in pancreatic endocrine tumors: analysis of gene and protein status in 169 sporadic neoplasms reveals alterations in the vast majority of cases. Endocrine-Related Cancer, 17(3), 771–783.PubMedCrossRefGoogle Scholar
  48. 48.
    Jiao, Y., Shi, C., Edil, B. H., de Wilde, R. F., Klimstra, D. S., Maitra, A., et al. (2011). DAXX/ATRX, MEN1, and mTOR pathway genes are frequently altered in pancreatic neuroendocrine tumors. Science, 331(6021), 1199–1203.PubMedCrossRefGoogle Scholar
  49. 49.
    Shida, T., Kishimoto, T., Furuya, M., Nikaido, T., Koda, K., Takano, S., et al. (2010). Expression of an activated mammalian target of rapamycin (mTOR) in gastroenteropancreatic neuroendocrine tumors. Cancer Chemotherapy and Pharmacology, 65(5), 889–893.PubMedCrossRefGoogle Scholar
  50. 50.
    Righi, L., Volante, M., Rapa, I., Tavaglione, V., Inzani, F., Pelosi, G., et al. (2010). Mammalian target of rapamycin signaling activation patterns in neuroendocrine tumors of the lung. Endocrine-Related Cancer, 17(4), 977–987.PubMedCrossRefGoogle Scholar
  51. 51.
    Pavel, M. E., Hainsworth, J. D., Baudin, E., Peeters, M., Horsch, D., Winkler, R. E., et al. (2011). 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, 378(9808), 2005–2012.PubMedCrossRefGoogle Scholar
  52. 52.
    Duran, I., Kortmansky, J., Singh, D., Hirte, H., Kocha, W., Goss, G., et al. (2006). A phase II clinical and pharmacodynamic study of temsirolimus in advanced neuroendocrine carcinomas. British Journal of Cancer, 95(9), 1148–1154.PubMedCrossRefGoogle Scholar
  53. 53.
    Cho, D., Signoretti, S., Dabora, S., Regan, M., Seeley, A., Mariotti, M., et al. (2007). Potential histologic and molecular predictors of response to temsirolimus in patients with advanced renal cell carcinoma. Clinical Genitourinary Cancer, 5(6), 379–385.PubMedCrossRefGoogle Scholar
  54. 54.
    Delbaldo, C., Albert, S., Dreyer, C., Sablin, M. P., Serova, M., Raymond, E., et al. (2011). Predictive biomarkers for the activity of mammalian target of rapamycin (mTOR) inhibitors. Targeted Oncology, 6(2), 119–124.PubMedCrossRefGoogle Scholar
  55. 55.
    Roldo, C., Missiaglia, E., Hagan, J. P., Falconi, M., Capelli, P., Bersani, S., et al. (2006). MicroRNA expression abnormalities in pancreatic endocrine and acinar tumors are associated with distinctive pathologic features and clinical behavior. Journal of Clinical Oncology, 24(29), 4677–4684.PubMedCrossRefGoogle Scholar
  56. 56.
    Volinia, S., Calin, G. A., Liu, C. G., Ambs, S., Cimmino, A., Petrocca, F., et al. (2006). A microRNA expression signature of human solid tumors defines cancer gene targets. Proceedings of the National Academy of Sciences of the United States of America, 103(7), 2257–2261.PubMedCrossRefGoogle Scholar
  57. 57.
    Svejda, B., Kidd, M., Kazberouk, A., Lawrence, B., Pfragner, R., & Modlin, I. M. (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(18), 4141–4154.PubMedCrossRefGoogle Scholar
  58. 58.
    Vilar, E., Salazar, R., Perez-Garcia, J., Cortes, J., Oberg, K., & Tabernero, J. (2007). Chemotherapy and role of the proliferation marker Ki-67 in digestive neuroendocrine tumors. Endocrine-Related Cancer, 14(2), 221–232.PubMedCrossRefGoogle Scholar
  59. 59.
    Tabernero, J., Rojo, F., Calvo, E., Burris, H., Judson, I., Hazell, K., et al. (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. Journal of Clinical Oncology, 26(10), 1603–1610.PubMedCrossRefGoogle Scholar
  60. 60.
    Yao, J. C., Phan, A. T., Chang, D. Z., Wolff, R. A., Hess, K., Gupta, S., et al. (2008). Efficacy of RAD001 (everolimus) and octreotide LAR in advanced low- to intermediate-grade neuroendocrine tumors: results of a phase II study. Journal of Clinical Oncology, 26(26), 4311–4318.PubMedCrossRefGoogle Scholar
  61. 61.
    Yao, J. C., Lombard-Bohas, C., Baudin, E., Kvols, L. K., Rougier, P., Ruszniewski, P., et al. (2010). Daily oral everolimus activity in patients with metastatic pancreatic neuroendocrine tumors after failure of cytotoxic chemotherapy: a phase II trial. Journal of Clinical Oncology, 28(1), 69–76.PubMedCrossRefGoogle Scholar
  62. 62.
    De Vries, E., Anthony, L. B., Sideris, L., Chen, L., Lebrec, J., Tsuchihashi, Z., et al. (2011). Effect of everolimus treatment on chromogranin A, neuron-specific enolase, gastrin, and glucagon levels in patients with advanced pancreatic neuroendocrine tumors (pNET): phase III RADIANT-3 Study results. ASCO Meeting Abstracts, 29(15_Suppl), 10624.Google Scholar
  63. 63.
    Yao, J. C., Ricci, S., Winkler, R. E., Jehl, V., & Pavel, M. E. (2011). Everolimus plus octreotide LAR versus placebo plus octreotide LAR in patients with advanced neuroendocrine tumors (NET): updated safety and efficacy results from RADIANT-2. ASCO Meeting Abstracts, 29(15_Suppl), 4011.Google Scholar
  64. 64.
    Yao, J. C., Phan, A. T., Fogleman, D., Ng, C. S., Jacobs, C. B., Dagohoy, C. D., et al. (2010). Randomized run-in study of bevacizumab (B) and everolimus (E) in low- to intermediate-grade neuroendocrine tumors (LGNETs) using perfusion CT as functional biomarker. ASCO Meeting Abstracts, 28(15_Suppl), 4002.Google Scholar
  65. 65.
    Yao, J. C., Phan, A., Hoff, P. M., Chen, H. X., Charnsangavej, C., Yeung, S. C., et al. (2008). Targeting vascular endothelial growth factor in advanced carcinoid tumor: a random assignment phase II study of depot octreotide with bevacizumab and pegylated interferon alpha-2b. Journal of Clinical Oncology, 26(8), 1316–1323.PubMedCrossRefGoogle Scholar
  66. 66.
    Ng, C. S., Charnsangavej, C., Wei, W., & Yao, J. C. (2011). Perfusion CT findings in patients with metastatic carcinoid tumors undergoing bevacizumab and interferon therapy. AJR. American Journal of Roentgenology, 196(3), 569–576.PubMedCrossRefGoogle Scholar
  67. 67.
    Ng, C. S., Wang, X., Faria, S. C., Lin, E., Charnsangavej, C., & Tannir, N. M. (2010). Perfusion CT in patients with metastatic renal cell carcinoma treated with interferon. AJR. American Journal of Roentgenology, 194(1), 166–171.PubMedCrossRefGoogle Scholar
  68. 68.
    Phan, A. T., Yao, J. C., Fogelman, D. R., Hess, K. R., Ng, C. S., Bullock, S. A., et al. (2010). A prospective, multi-institutional phase II study of GW786034 (pazopanib) and depot octreotide (sandostatin LAR) in advanced low-grade neuroendocrine carcinoma (LGNEC). ASCO Meeting Abstracts, 28(15_Suppl), 4001.Google Scholar
  69. 69.
    Cui, T., Hurtig, M., Elgue, G., Li, S. C., Veronesi, G., Essaghir, A., et al. (2010). Paraneoplastic antigen Ma2 autoantibodies as specific blood biomarkers for detection of early recurrence of small intestine neuroendocrine tumors. PLoS One, 5(12), e16010.PubMedCrossRefGoogle Scholar
  70. 70.
    Khan, M. S., Tsigani, T., Rashid, M., Rabouhans, J. S., Yu, D., Luong, T. V., et al. (2011). Circulating tumor cells and EpCAM expression in neuroendocrine tumors. Clinical Cancer Research, 17(2), 337–345.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Sara De Dosso
    • 1
  • Enrique Grande
    • 2
  • Jorge Barriuso
    • 3
  • Daniel Castellano
    • 4
  • Josep Tabernero
    • 5
  • Jaume Capdevila
    • 5
    • 6
  1. 1.Oncology Institute of Southern SwitzerlandBellinzonaSwitzerland
  2. 2.Ramón y Cajal University HospitalMadridSpain
  3. 3.La Paz University HospitalMadridSpain
  4. 4.Doce de Octubre University HospitalMadridSpain
  5. 5.Vall d’Hebron University HospitalBarcelonaSpain
  6. 6.Department of Medical OncologyVall d’Hebron University HospitalBarcelonaSpain

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