Novel therapeutics and drug-delivery approaches in the modulation of glioblastoma stem cell resistance

Ther Deliv. 2022 Apr;13(4):249-273. doi: 10.4155/tde-2021-0086. Epub 2022 May 26.

Abstract

Glioblastoma (GBM) is a deadly malignancy with a poor prognosis. An important factor contributing to GBM recurrence is high resistance of GBM cancer stem cells (GSCs). While temozolomide (TMZ), has been shown to consistently extend survival, GSCs grow resistant to TMZ through upregulation of DNA damage repair mechanisms and avoidance of apoptosis. Since a single-drug approach has failed to significantly alter prognosis in the past 15 years, unique approaches such as multidrug combination therapy together with distinctive targeted drug-delivery approaches against cancer stem cells are needed. In this review, a rationale for multidrug therapy using a targeted nanotechnology approach that preferentially target GSCs is proposed with discussion and examples of drugs, nanomedicine delivery systems, and targeting moieties.

Keywords: CD44; CD133; CSC; GBM; aptamers; cancer stem cells; glioblastoma; idasanutlin; liposome; nanomedicine; nanoparticle; nestin; paclitaxel; solid-lipid nanoparticle; temozolomide; theranostics.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain Neoplasms* / drug therapy
  • Brain Neoplasms* / pathology
  • Cell Line, Tumor
  • Drug Resistance, Neoplasm
  • Drug Therapy, Combination
  • Glioblastoma* / drug therapy
  • Humans
  • Leprostatic Agents / pharmacology
  • Leprostatic Agents / therapeutic use
  • Neoplastic Stem Cells / pathology
  • Temozolomide / pharmacology
  • Temozolomide / therapeutic use

Substances

  • Leprostatic Agents
  • Temozolomide