Neuroendocrine tumors. Molecular targeted therapy for carcinoid and islet-cell carcinoma

Best Pract Res Clin Endocrinol Metab. 2007 Mar;21(1):163-72. doi: 10.1016/j.beem.2007.01.006.


Carcinoid and islet-cell carcinoma are often also known as low-grade neuroendocrine carcinomas. They are often slow-growing but can be resistant to standard therapy. While somatostatin analogues are often used to control hormonal syndromes, there is currently no therapy approved in the US for control of carcinoid tumor growth. For islet-cell carcinoma, streptozocin-based chemotherapy may induce tumor shrinkage, but second-line option are limited. This chapter reviews the molecular biology of neuroendocrine tumors, including the roles of MENIN, TSC2, NF-1, vHL, p53, bcl-2, bax, VEGF, IGF, PDGF, EGFR, and mTOR. Recently, there has been interest in developing molecularly targeted therapy for this group of diseases. Phase-II studies with imatinib, bevacizumab, sunitinib, gefitnib, temsirolimus, and everolimus (RAD001) have completed accrual. Encouraging results have been observed in studies with VEGF and mTOR inhibitors. Phase-III study of bevacizumab is planned in the US. Large-scale multinational phase-II and -III studies of everolimus are under way.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Biomarkers, Tumor / genetics
  • Carcinoma, Islet Cell / genetics
  • Carcinoma, Islet Cell / therapy*
  • Gene Targeting*
  • Genes, abl
  • Genes, erbB-1
  • Genetic Therapy*
  • Humans
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / therapy
  • Neuroendocrine Tumors / genetics
  • Neuroendocrine Tumors / therapy*
  • Pancreas / blood supply
  • Pancreatic Neoplasms / blood supply
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / therapy*
  • Protein Kinases / genetics
  • Proto-Oncogene Proteins c-kit / genetics
  • Proto-Oncogene Proteins c-ret / genetics
  • Receptors, Platelet-Derived Growth Factor / genetics
  • TOR Serine-Threonine Kinases


  • Biomarkers, Tumor
  • Protein Kinases
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-kit
  • Proto-Oncogene Proteins c-ret
  • RET protein, human
  • Receptors, Platelet-Derived Growth Factor