New strategies for advanced neuroendocrine tumors in the era of targeted therapy

Clin Cancer Res. 2012 Apr 1;18(7):1830-6. doi: 10.1158/1078-0432.CCR-11-2105. Epub 2012 Feb 15.


Low- to intermediate-grade neuroendocrine tumor (NET) constitutes a group of indolent malignancies that share the capacity for secreting hormones and neuroamines. Until recently, there were few therapeutic options for oncologic control. The PROMID study showed that octreotide long-acting repeatable formulation can delay tumor growth in midgut NETs. And, recent phase III studies showed both everolimus and sunitinib improved progression-free survival in pancreatic NETs, validating the phosphoinositide 3-kinase/Akt/mTOR pathway and angiogenesis as important targets for further advances. Ongoing and planned pivotal studies targeting these pathways in other NET subtypes may widen their therapeutic application. Development of rational combinations may further improve therapeutic outcome. These successes and our improved understanding of the underlying molecular biology are likely to lead to further important advances on the horizon.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Disease-Free Survival
  • Drug Therapy / methods*
  • Drug Therapy / trends
  • Everolimus
  • Humans
  • Indoles / therapeutic use
  • Models, Biological
  • Neuroendocrine Tumors / drug therapy*
  • Neuroendocrine Tumors / metabolism
  • Neuroendocrine Tumors / pathology
  • Octreotide / therapeutic use
  • Pancreas / drug effects
  • Pancreas / metabolism
  • Pancreas / pathology
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Pyrroles / therapeutic use
  • Signal Transduction / drug effects*
  • Sirolimus / analogs & derivatives
  • Sirolimus / therapeutic use
  • Sunitinib
  • TOR Serine-Threonine Kinases / metabolism


  • Antineoplastic Agents
  • Indoles
  • Pyrroles
  • Everolimus
  • Phosphatidylinositol 3-Kinases
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Octreotide
  • Sunitinib
  • Sirolimus