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Updated: Mar 2, 2026

A Rapid Screening Workflow to Identify Potential Combination Therapy for GBM using Patient-Derived Glioma Stem Cells
05:29

A Rapid Screening Workflow to Identify Potential Combination Therapy for GBM using Patient-Derived Glioma Stem Cells

Published on: March 28, 2021

3.2K

GPI inactivation mediates pentose phosphate pathway flux switch-on inducing temozolomide resistance in glioma stem

Jianxing Yin1, Zelei Du1, Xingdong Liu2

  • 1Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210000, PR China.

Cancer Letters
|February 28, 2026
PubMed

Insights

Glioblastoma stem cells resist chemotherapy by boosting the pentose phosphate pathway (PPP). The ATM/PLK1/GPI pathway is key to this resistance, offering new therapeutic targets for glioblastoma (GBM).

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Glioblastoma (GBM) chemoresistance, particularly in glioma stem cells (GSCs), is a major clinical hurdle.
  • Targeting GSCs is a promising strategy to combat GBM recurrence and treatment failure.

Purpose of the Study:

  • To investigate the mechanisms underlying temozolomide (TMZ) resistance in GSCs.
  • To identify potential therapeutic targets and biomarkers for GBM treatment.

Main Methods:

  • Comparative analysis of pentose phosphate pathway (PPP) flux in GSCs versus differentiated cells.
  • Investigating the role of the ATM/PLK1/GPI signaling axis in regulating GSC chemoresistance.
  • Assessing the impact of targeting this axis with rigosertib.

Main Results:

  • GSCs exhibit increased PPP flux, contributing to TMZ resistance.
  • TMZ treatment activates ATM, leading to PLK1 nuclear export and subsequent phosphorylation and suppression of glucose-6-phosphate isomerase (GPI) activity.
  • Targeting the ATM/PLK1/GPI axis with rigosertib shows therapeutic potential.

Conclusions:

  • The ATM/PLK1/GPI axis is crucial for regulating PPP flux and TMZ resistance in GSCs.
  • PLK1 expression and GPI pT215 levels may serve as predictive biomarkers for GBM.
  • Combinational therapy targeting this axis offers a potential strategy to overcome GBM chemoresistance.

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