Role of biological targeted therapies in gastroenteropancreatic neuroendocrine tumours
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Approximately two-thirds of neuroendocrine tumours (NET) occur in the gastrointestinal tract and over 60% present with metastases. With greater insight into molecular pathways involved in tumour progression, opportunities are presented for the use of targeted therapies in NET. Although a wide array of targeted agents has been investigated, only a handful has emerged as forerunners from recent clinical trials. This literature review focuses on the use of anti-angiogenic monoclonal antibody bevacizumab, as well as small molecule inhibitors sunitinib and everolimus.
KeywordsBevacizumab Carcinoid Everolimus Neuroendocrine Pancreatic Sunitinib
NHS funding to the NIHR Biomedical Research Centre is acknowledged.
Conflict of interest
The author has no conflict of interest to declare.
- 3.J. Zhang, Z. Jia, Q. Li, L. Wang, A. Rashid, Z. Zhu, D.B. Evans, J.N. Vauthey, K. Xie, J.C. Yao, Elevated expression of vascular endothelial growth factor correlates with increased angiogenesis and decreased progression-free survival among patients with low-grade neuroendocrine tumors. Cancer 109, 1478–1486 (2007)PubMedCrossRefGoogle Scholar
- 4.S.R. Silva, K.A. Bowen, P.G. Rychahou, L.N. Jackson, H.L. Weiss, E.Y. Lee, C.M. Townsend Jr, B.M. Evers, VEGFR-2 expression in carcinoid cancer cells and its role in tumor growth and metastasis. Int. J. Cancer 128, 1045–1056 (2011)Google Scholar
- 6.J.C. Yao, A. Phan, P.M. Hoff, H.X. Chen, C. Charnsangavej, S.C. Yeung, K. Hess, C. Ng, J.L. Abbruzzese, J.A. Ajani, 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. J. Clin. Oncol. 26, 1316–1323 (2008)PubMedCrossRefGoogle Scholar
- 9.T.J. Hobday, J. Rubin, K. Holen, J. Picus, R. Donehower, R. Marschke, W. Maples, R. Lloyd, M. Mahoney, C. Erlichman, MC044h, a phase II trial of sorafenib in patients (pts) with metastatic neuroendocrine tumors (NET): A phase II Consortium (P2C) study. J. Clin. Oncol. 25, abstract 4504 (2007)Google Scholar
- 11.J.C. Yao, A.T. Phan, D.Z. Chang, R.A. Wolff, K. Hess, S. Gupta, C. Jacobs, J.E. Mares, A.N. Landgraf, A. Rashid, 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 (2008)PubMedCrossRefGoogle Scholar
- 12.J.C. Yao, C. Lombard-Bohas, E. Baudin, L.K. Kvols, P. Rougier, P. Ruszniewski, S. Hoosen, J. St.Peter, T. Haas, D. Lebwohl, 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 (2010)PubMedCrossRefGoogle Scholar
- 14.M.H. Shah, T. Ito, C. Lombard-Bohas, E.M. Wolin, E. Van Cutsem, C. Sachs, R.E. Winkler, J. Lincy, T.J. Hobday, J.C. Yao, Everolimus in patients with advanced pancreatic neuroendocrine tumors (pNET): Updated results of a randomized, double-blind, placebo-controlled, multicenter phase III trial (RADIANT-3). J. Clin. Oncol. 29, 158 (2011)CrossRefGoogle Scholar
- 15.J.C. Yao, J.D. Hainsworth, E. Baudin, M. Peeters, D. Hoersch, L.B. Anthony, J. Klimovsky, K. Grouss, V. Jehl, M. Pavel, Everolimus plus octreotide LAR (E + O) versus placebo plus octreotide LAR (P + O) in patients with advanced neuroendocrine tumors (NET): Updated results of a randomized, double-blind, placebo-controlled, multicenter phase III trial (RADIANT-2). J Clin Oncol 29, 159 (2011)CrossRefGoogle Scholar
- 16.J.C. Yao, A.T. Phan, D. Fogleman, C.S. Ng, C.B. Jacobs, C.D. Dagohoy, C. Leary, K.R. Hess, 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. 28, abstract 4002 (2010)Google Scholar
- 18.G. Vitale, P.M. van Koetsveld, W.W. de Herder, K. van der Wansem, J.A. Janssen, A. Colao, G. Lombardi, S.W. Lamberts, L.J. Hofland, Effects of type I interferons on IGF-mediated autocrine/paracrine growth of human neuroendocrine tumor cells. Am. J. Physiol. Endocrinol. Metab. 296(3), E559–E566 (2009)PubMedCrossRefGoogle Scholar
- 19.A.W. Tolcher, M.L. Rothenberg, J. Rodon, D. Delbeke, A. Patnaik, L. Nguyen, F. Young, Y. Hwang, C. Haqq, I. Puzanov, Phase I, pharmacokinetic, and pharmacodynamic study of AMG 479, a fully human monoclonal antibody to insulin-like growth factor receptor 1. J. Clin. Oncol. 27, 5800–5807 (2009)PubMedCrossRefGoogle Scholar
- 20.D.L. Reidy, E. Hollywood, M. Segal, L. Saltz, A phase II clinical trial of MK-0646, an insulin-like growth factor-1 receptor inhibitor (IGF-1R), in patients with metastatic well-differentiated neuroendocrine tumors (NETs). ASCO Meeting Abstracts, vol. 28 (2010), p. 4163Google Scholar
- 21.L. Kvols, B. Wiedenmann, K. Oberg, J. Glusman, T. O’Dorisio, W. de Herder, B. Gao, R. Arnold, L. Anthony, SOM230 Carcinoid Study Group, Safety and efficacy of pasireotide (SOM230) in patients with metastatic carcinoid tumors refractory or resistant to octreotide LAR: Results of a phase II study. ASCO Gastrointestinal Cancers Symposium, Abstract 171, 2006Google Scholar
- 22.K.E. Oberg, J.C. Reubi, D.J. Kwekkeboom, E.P. Krenning, Role of somatostatins in gastroenteropancreatic neuroendocrine tumor development and therapy. Gastroenterology 139(3), 742–753, 753.e1 (2010)Google Scholar
- 23.M. Caraglia, M. Marra, P. Tagliaferri, S.W. Lamberts, S. Zappavigna, G. Misso, F. Cavagnini, G. Facchini, A. Abbruzzese, L.J. Hofland, G. Vitale, Emerging strategies to strengthen the anti-tumour activity of type I interferons: overcoming survival pathways. Curr. Cancer Drug Targets 9(5), 690–704 (2009)PubMedCrossRefGoogle Scholar
- 24.E. Allen, I.B. Walters, D. Hanahan, Brivanib, a dual FGF/VEGF inhibitor, is active both first and second line against mouse pancreatic neuroendocrine tumors developing adaptive/evasive resistance to VEGF inhibition. Clin. Cancer Res. 17(16), 5299–5310 (2011)Google Scholar
- 25.E.A. Eisenhauer, P. Therasse, J. Bogaerts, L.H. Schwartz, D. Sargent, R. Ford, J. Dancey, S. Arbuck, S. Gwyther, M. Mooney, L. Rubinstein, L. Shankar, L. Dodd, R. Kaplan, D. Lacombe, J. Verweij, New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur. J. Cancer 45, 228–247 (2009)PubMedCrossRefGoogle Scholar