The Importance of Tumor Stem Cells in Glioblastoma Resistance to Therapy

Int J Mol Sci. 2021 Apr 8;22(8):3863. doi: 10.3390/ijms22083863.

Abstract

Glioblastoma (GBM) is known to be the most common and lethal primary malignant brain tumor. Therapies against this neoplasia have a high percentage of failure, associated with the survival of self-renewing glioblastoma stem cells (GSCs), which repopulate treated tumors. In addition, despite new radical surgery protocols and the introduction of new anticancer drugs, protocols for treatment, and technical advances in radiotherapy, no significant improvement in the survival rate for GBMs has been realized. Thus, novel antitarget therapies could be used in conjunction with standard radiochemotherapy approaches. Targeted therapy, indeed, may address specific targets that play an essential role in the proliferation, survival, and invasiveness of GBM cells, including numerous molecules involved in signal transduction pathways. Significant cellular heterogeneity and the hierarchy with GSCs showing a therapy-resistant phenotype could explain tumor recurrence and local invasiveness and, therefore, may be a target for new therapies. Therefore, the forced differentiation of GSCs may be a promising new approach in GBM treatment. This article provides an updated review of the current standard and experimental therapies for GBM, as well as an overview of the molecular characteristics of GSCs, the mechanisms that activate resistance to current treatments, and a new antitumor strategy for treating GSCs for use as therapy.

Keywords: cancer stem cells; glioblastoma; glioblastoma stem cells; glioblastoma stem cells and therapy resistance; glioblastoma therapy resistance; new drugs in the treatment of glioblastoma stem cells.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Biomarkers
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / etiology
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Cell Differentiation
  • Cell Self Renewal
  • Disease Susceptibility
  • Drug Resistance, Neoplasm* / genetics
  • Glioblastoma / drug therapy
  • Glioblastoma / etiology
  • Glioblastoma / metabolism*
  • Glioblastoma / pathology
  • Humans
  • Neoplastic Stem Cells / drug effects*
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / pathology
  • Signal Transduction / drug effects

Substances

  • Antineoplastic Agents
  • Biomarkers