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Updated: Jun 19, 2026
Evaluating In Vitro DNA Damage Using Comet Assay
Published on: October 11, 2017
Perspective on the Use of DNA Repair Inhibitors as a Tool for Imaging and Radionuclide Therapy of Glioblastoma
Liesbeth Everix1, Shankari Nair2, Cathryn H S Driver3,4
1Molecular Imaging Center Antwerp (MICA), University of Antwerp, 2610 Wilrijk, Belgium.
Abstract:
Despite numerous innovative treatment strategies, the treatment of glioblastoma (GB) remains challenging. With the current state-of-the-art therapy, most GB patients succumb after about a year. In the evolution of personalized medicine, targeted radionuclide therapy (TRT) is gaining momentum, for example, to stratify patients based on specific biomarkers. One of these biomarkers is deficiencies in DNA damage repair (DDR), which give rise to genomic instability and cancer initiation. However, these deficiencies also provide targets to specifically kill cancer cells following the synthetic lethality principle. This led to the increased interest in targeted drugs that inhibit essential DDR kinases (DDRi), of which multiple are undergoing clinical validation. In this review, the current status of DDRi for the treatment of GB is given for selected targets: ATM/ATR, CHK1/2, DNA-PK, and PARP. Furthermore, this review provides a perspective on the use of radiopharmaceuticals targeting these DDR kinases to (1) evaluate the DNA repair phenotype of GB before treatment decisions are made and (2) induce DNA damage via TRT. Finally, by applying in-house selection criteria and analyzing the structural characteristics of the DDRi, four drugs with the potential to become new therapeutic GB radiopharmaceuticals are suggested.
Insights
Targeted radionuclide therapy (TRT) shows promise for glioblastoma (GB) by targeting DNA damage repair (DDR) deficiencies. This approach could personalize treatment and improve patient outcomes by inhibiting DDR kinases.
Area of Science:
- Oncology
- Molecular Biology
- Radiochemistry
Background:
- Glioblastoma (GB) treatment remains challenging, with limited patient survival.
- Personalized medicine strategies, including targeted radionuclide therapy (TRT), are emerging.
- Deficiencies in DNA damage repair (DDR) are key biomarkers and therapeutic targets in cancer.
Purpose of the Study:
- To review the current status of DNA damage repair inhibitors (DDRi) for glioblastoma treatment.
- To explore the potential of radiopharmaceuticals targeting DDR kinases for GB therapy.
- To identify novel therapeutic radiopharmaceuticals for glioblastoma.
Main Methods:
- Review of current DNA damage repair inhibitors (DDRi) targeting ATM/ATR, CHK1/2, DNA-PK, and PARP.
- Analysis of radiopharmaceuticals for evaluating DNA repair phenotypes and inducing DNA damage via TRT.
- In-house selection criteria and structural analysis of DDRi for potential radiopharmaceutical development.
Main Results:
- Multiple DDRi are under clinical validation for glioblastoma treatment.
- Radiopharmaceuticals offer a dual approach: assessing DNA repair status and delivering targeted therapy.
- Four potential DDRi candidates were identified for development as therapeutic GB radiopharmaceuticals.
Conclusions:
- Targeted radionuclide therapy (TRT) combined with DDR inhibitors presents a promising avenue for glioblastoma treatment.
- Radiopharmaceuticals can personalize glioblastoma therapy by evaluating DNA repair phenotypes.
- Further development of DDRi-based radiopharmaceuticals could significantly improve glioblastoma patient outcomes.
