Cell survival signaling in neuroblastoma

Anticancer Agents Med Chem. 2013 May;13(4):563-75. doi: 10.2174/1871520611313040005.

Abstract

Neuroblastoma is the most common extracranial solid tumor of childhood and is responsible for over 15% of pediatric cancer deaths. Neuroblastoma tumorigenesis and malignant transformation is driven by overexpression and dominance of cell survival pathways and a lack of normal cellular senescence or apoptosis. Therefore, manipulation of cell survival pathways may decrease the malignant potential of these tumors and provide avenues for the development of novel therapeutics. This review focuses on several facets of cell survival pathways including protein kinases (PI3K, AKT, ALK, and FAK), transcription factors (NF-κB, MYCN and p53), and growth factors (IGF, EGF, PDGF, and VEGF). Modulation of each of these factors decreases the growth or otherwise hinders the malignant potential of neuroblastoma, and many therapeutics targeting these pathways are already in the clinical trial phase of development. Continued research and discovery of effective modulators of these pathways will revolutionize the treatment of neuroblastoma.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Cell Survival / drug effects
  • Humans
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Neuroblastoma / drug therapy
  • Neuroblastoma / metabolism
  • Neuroblastoma / pathology*
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinases / metabolism
  • Signal Transduction* / drug effects
  • Transcription Factors / metabolism

Substances

  • Antineoplastic Agents
  • Intercellular Signaling Peptides and Proteins
  • Protein Kinase Inhibitors
  • Transcription Factors
  • Protein Kinases