PI3K-AKT-mTOR-signaling and beyond: the complex network in gastroenteropancreatic neuroendocrine neoplasms

Theranostics. 2014 Jan 29;4(4):336-65. doi: 10.7150/thno.7851. eCollection 2014.

Abstract

Gastroenteropancreatic neuroendocrine neoplasms are heterogeneous in their clinical behavior and require therapies specially tailored according to staging, grading, origin and expression of peptide receptors. Despite extensive scientific efforts, the therapy options are still not satisfactory. The main reasons are due to the lack of a broad mechanistic knowledge, an insufficient classification of specific diagnostic sub-groups, and predictive markers. GEP-NEN tumors evade early diagnosis because of slow asymptomatic growth behavior and are frequently not detected until metastasized. How signaling networks contribute to tumor progression and how these networks interact remains unclear in large parts. In this review we summarize the knowledge on the growth factor responsive non-angiogenetic pathways in sporadic GEP-NENs, highlight promising mechanistic research approaches, and describe important therapy targets.

Keywords: Gastroenteropancreatic neuroendocrine neoplasms; biotherapy; growth factors; inhibitor.; kinases; molecular biology; signal transduction.

Publication types

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

MeSH terms

  • Animals
  • ErbB Receptors / metabolism
  • Gastrointestinal Neoplasms / metabolism*
  • Gastrointestinal Neoplasms / therapy
  • Humans
  • Molecular Targeted Therapy
  • Neuroendocrine Tumors / metabolism*
  • Neuroendocrine Tumors / therapy
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / therapy
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Receptor, IGF Type 1 / metabolism
  • Signal Transduction
  • Somatostatin / metabolism
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • Somatostatin
  • Phosphatidylinositol 3-Kinases
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • ErbB Receptors
  • Receptor, IGF Type 1
  • Proto-Oncogene Proteins c-akt