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Updated: Feb 25, 2026
A Rapid Screening Workflow to Identify Potential Combination Therapy for GBM using Patient-Derived Glioma Stem Cells
Published on: March 28, 2021
GBM radiosensitizers: dead in the water…or just the beginning?
Ranjit S Bindra1, Anthony J Chalmers2, Sydney Evans3
1Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT, 06520, USA. ranjit.bindra@yale.edu.
Abstract:
The finding that most GBMs recur either near or within the primary site after radiotherapy has fueled great interest in the development of radiosensitizers to enhance local control. Unfortunately, decades of clinical trials testing a wide range of novel therapeutic approaches have failed to yield any clinically viable radiosensitizers. However, many of the previous radiosensitizing strategies were not based on clear pre-clinical evidence, and in many cases blood-barrier penetration was not considered. Furthermore, DNA repair inhibitors have only recenly arrived in the clinic, and likely represent potent agents for glioma radiosensitization. Here, we present recent progress in the use of small molecule DNA damage response inhibitors as GBM radiosensitizers. In addition, we discuss the latest progress in targeting hypoxia and oxidative stress for GBM radiosensitization.
Insights
Most glioblastomas (GBMs) recur locally after radiotherapy, driving research into radiosensitizers. Recent progress focuses on DNA damage response inhibitors, hypoxia, and oxidative stress to improve GBM radiosensitization and local control.
Area of Science:
- Oncology
- Radiotherapy
- Molecular Biology
Background:
- Glioblastomas (GBMs) frequently recur locally post-radiotherapy, necessitating improved local control strategies.
- Decades of clinical trials have not identified effective radiosensitizers for GBM treatment.
- Previous strategies often lacked robust preclinical evidence or failed to consider blood-brain barrier penetration.
Purpose of the Study:
- To review recent advancements in using small molecule DNA damage response inhibitors as GBM radiosensitizers.
- To discuss emerging strategies targeting hypoxia and oxidative stress for enhanced GBM radiosensitization.
Main Methods:
- Review of recent preclinical and clinical research on GBM radiosensitization.
- Focus on small molecule inhibitors targeting DNA damage response pathways.
- Exploration of novel approaches including hypoxia and oxidative stress modulation.
Main Results:
- DNA repair inhibitors show promise as potent agents for glioma radiosensitization.
- Targeting hypoxia and oxidative stress are emerging as viable strategies.
- Small molecule inhibitors represent a promising avenue for overcoming radiotherapy resistance.
Conclusions:
- Small molecule DNA damage response inhibitors are a key area of progress for GBM radiosensitization.
- Addressing hypoxia and oxidative stress offers further potential to enhance radiotherapy efficacy.
- Future research should focus on clinically viable radiosensitizers with improved blood-brain barrier penetration.
