Prognostic and predictive role of the PI3K-AKT-mTOR pathway in neuroendocrine neoplasms

Clin Transl Oncol. 2018 May;20(5):561-569. doi: 10.1007/s12094-017-1758-3. Epub 2017 Nov 9.

Abstract

Neuroendocrine neoplasms (NENs) are considered a heterogeneous and rare entity. Its natural history is influenced by multiple clinicopathological characteristics, which guide the management of these patients. The development of molecular biology reveals that the PI3K-AKT-mTOR pathway plays a relevant role in tumorigenesis and progression of NENs. Mammalian target of rapamycin (mTOR) inhibitors, targeted agents that block this pathway, has improved outcomes in neuroendocrine tumors (NETs). Different therapeutic approaches, such as somatostatin analogs, chemotherapy, peptide receptor radionuclide therapy, and targeted agents, have shown benefits in the treatment of NETs. However, there are not any established prognostic or predictive biomarkers to select the best therapy option to individualize treatment. Although a relation between alterations in the PI3K-AKT-mTOR pathway and clinical outcomes has not been found, these anomalies are considered attractive biomarkers. Additional molecular analysis should be integrated in future clinical trials' design to identify potential predictive or prognostic biomarkers.

Keywords: Neuroendocrine neoplasm; Neuroendocrine tumors; PI3K–AKT–mTOR pathway; Predictive; Prognostic; mTOR Inhibitors.

Publication types

  • Review

MeSH terms

  • Biomarkers, Tumor / analysis*
  • Humans
  • Molecular Targeted Therapy
  • Neuroendocrine Tumors / pathology*
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction / physiology
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • Biomarkers, Tumor
  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases