The role of glioma stem cells in chemotherapy resistance and glioblastoma multiforme recurrence

Expert Rev Neurother. 2015;15(7):741-52. doi: 10.1586/14737175.2015.1051968. Epub 2015 May 31.

Abstract

Glioma stem cells (GSCs) constitute a slow-dividing, small population within a heterogeneous glioblastoma. They are able to self-renew, recapitulate a whole tumor, and differentiate into other specific glioblastoma multiforme (GBM) subpopulations. Therefore, they have been held responsible for malignant relapse after primary standard therapy and the poor prognosis of recurrent GBM. The failure of current therapies to eliminate specific GSC subpopulations has been considered a major factor contributing to the inevitable recurrence in GBM patients after treatment. Here, we discuss the molecular mechanisms of chemoresistance of GSCs and the reasons why complete eradication of GSCs is so difficult to achieve. We will also describe the targeted therapies currently available for GSCs and possible mechanisms to overcome such chemoresistance and avoid therapeutic relapse.

Keywords: chemoresistance; glioma stem cells; malignant glioma; mechanisms; plasticity; recurrence.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / adverse effects*
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / physiopathology*
  • Glioblastoma / drug therapy*
  • Glioblastoma / physiopathology*
  • Glioma / pathology*
  • Humans
  • Neoplasm Recurrence, Local
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / physiology*

Substances

  • Antineoplastic Agents