Targeting glioma stem cells: a novel framework for brain tumors

Cancer Sci. 2011 Nov;102(11):1958-66. doi: 10.1111/j.1349-7006.2011.02064.x. Epub 2011 Sep 16.

Abstract

The past decade has seen a dramatic increase in stem cell research that focuses on glioma stem cells (GSC) and their mechanisms of action, revealing multiple potential targets for primary malignant brain tumors. Herein, we present a novel framework for considering GSC targets based on direct and indirect strategies. Direct strategies target GSC molecular pathways to overcome their resistance to radiation and chemotherapy, block their function or induce their differentiation. Indirect strategies target the microenvironment of the GSC, namely the perivascular, hypoxic and immune niches. Progress made on GSC targets is reviewed in detail and specific pathways are identified in context of the proposed framework. The potential barriers for translation to the clinical setting are also discussed. Overall, targeting GSC provides an unprecedented opportunity for revolutionary approaches to treat high-grade gliomas that continue to have a poor patient prognosis.

Publication types

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

MeSH terms

  • Angiogenesis Inhibitors / pharmacology
  • Angiogenesis Inhibitors / therapeutic use
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / pathology*
  • Brain Neoplasms / radiotherapy
  • Cell Differentiation / drug effects
  • Cell Hypoxia / drug effects
  • Cellular Microenvironment / drug effects
  • Cellular Microenvironment / immunology
  • DNA Methylation / drug effects
  • DNA Repair / drug effects
  • DNA Repair / radiation effects
  • Drug Resistance, Neoplasm
  • Gene Expression Regulation, Neoplastic / drug effects
  • Glioma / drug therapy
  • Glioma / pathology*
  • Glioma / radiotherapy
  • Humans
  • Intercellular Signaling Peptides and Proteins / physiology
  • Models, Biological
  • Molecular Targeted Therapy*
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / physiology
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / pathology*
  • Neoplastic Stem Cells / radiation effects
  • Radiation Tolerance
  • Signal Transduction / drug effects
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / radiation effects

Substances

  • Angiogenesis Inhibitors
  • Antineoplastic Agents
  • Intercellular Signaling Peptides and Proteins
  • Neoplasm Proteins