PI3King the lock: targeting the PI3K/Akt/mTOR pathway as a novel therapeutic strategy in neuroblastoma

J Pediatr Hematol Oncol. 2015 May;37(4):245-51. doi: 10.1097/MPH.0000000000000329.

Abstract

Neuroblastoma is the most common extracranial cancer in childhood. High-risk neuroblastoma continues to have a poor prognosis and there is an urgent need to design biologically based therapies that specifically target the pathways responsible for malignant transformation and progression. One such pathway is the PI3K/Akt/mTOR pathway. In this article we outline the evidence for aberrant activation of the PI3K/Akt/mTOR pathway in neuroblastoma and discuss the possible mechanisms which mediate it. We also discuss the development of treatments targeting this pathway in neuroblastoma and the challenges that must be overcome before such treatments can enter routine clinical practice.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Mechanistic Target of Rapamycin Complex 1
  • Mechanistic Target of Rapamycin Complex 2
  • Multiprotein Complexes / antagonists & inhibitors
  • Neuroblastoma / drug therapy*
  • Neuroblastoma / etiology
  • Phosphatidylinositol 3-Kinases / physiology
  • Phosphoinositide-3 Kinase Inhibitors*
  • Protein Kinase Inhibitors / therapeutic use*
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-akt / physiology
  • Signal Transduction / drug effects*
  • Signal Transduction / physiology
  • TOR Serine-Threonine Kinases / antagonists & inhibitors*
  • TOR Serine-Threonine Kinases / physiology

Substances

  • Multiprotein Complexes
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Kinase Inhibitors
  • Mechanistic Target of Rapamycin Complex 1
  • Mechanistic Target of Rapamycin Complex 2
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases