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Decreased eukaryotic initiation factors expression upon temozolomide treatment-potential novel implications for eIFs

Stefanie Krassnig1, Stefan L Leber1,2, Andrea Orthmann3

  • 1Diagnostic & Research Center for Molecular BioMedicine, Department of Neuropathology, Institute of Pathology, Medical University of Graz, Graz, Austria.

Journal of Neuro-Oncology
|November 1, 2023
PubMed
Abstract

Insights

New research suggests eukaryotic initiation factors (eIFs) could be key targets for improving glioma treatment. Combination therapy with regorafenib and temozolomide (TMZ) may restore eIF pathway function in resistant tumors.

Area of Science:

  • Neuro-oncology
  • Cancer Biology
  • Molecular Medicine

Background:

  • Glioma treatment remains challenging due to tumor heterogeneity.
  • Eukaryotic initiation factors (eIFs) show altered expression in various cancers, including gliomas.

Purpose of the Study:

  • To investigate the potential of eIFs as novel therapeutic targets for glioma.
  • To evaluate the impact of chemotherapy on eIF expression and regulation in gliomas.

Main Methods:

  • Analysis of eIF protein expression in 22 glioblastoma patient-derived xenografts (GBM PDX).
  • Assessment of eIF regulation following treatment with cytostatics.
  • Evaluation in relation to GBM PDX mutation profile analyses.

Main Results:

  • Temozolomide (TMZ) treatment led to decreased eIF expression, independent of the PI3K/AKT/mTOR pathway.
  • These TMZ effects were absent in TMZ-resistant PDX models.
  • Combination therapy with regorafenib and TMZ restored the eIF/AKT/mTOR signaling axis.

Conclusions:

  • Chemotherapy significantly impacts eIF regulation in gliomas.
  • eIFs represent promising targets for enhancing future glioma therapies.
  • Further research into eIFs may lead to improved treatment strategies for gliomas.
Keywords:
AstrocytomaEukaryotic initiation factorsGliomaGlioma therapyTemozolomide

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