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Published on: September 27, 2024
Recent developments in drug delivery strategies for targeting DNA damage response in glioblastoma
A M Morás1, J G Henn1, L Steffens Reinhardt1
1Laboratory of Genetic Toxicology, Federal University of Health Sciences of Porto Alegre, (UFCSPA), Porto Alegre, Brazil.
Abstract:
Glioblastoma is the most frequent and malignant brain tumor. The median survival for this disease is approximately 15 months, and despite all the available treatment strategies employed, it remains an incurable disease. Preclinical and clinical research have shown that the resistance process related to DNA damage repair pathways, glioma stem cells, blood-brain barrier selectivity, and dose-limiting toxicity of systemic treatment leads to poor clinical outcomes. In this context, the advent of drug delivery systems associated with localized treatment seems to be a promising and versatile alternative to overcome the failure of the current treatment approaches. In order to bypass therapeutic tumor resistance mechanisms, more effective combinatorial therapies should be identified, such as the use of cytotoxic drugs combined with the inhibition of DNA damage response (DDR)-related targets. Additionally, critical reasoning about the delivery approach and administration route in brain tumors treatment innovation is essential. The outcomes of future experimental studies regarding the association of delivery systems, alternative treatment routes, and DDR targets are expected to lead to the development of refined therapeutic interventions. Novel therapeutic approaches could improve the life's quality of glioblastoma patients and increase their survival rate.
Insights
Glioblastoma treatment faces challenges due to drug resistance and delivery issues. Novel drug delivery systems and targeting DNA damage response pathways offer promising strategies to improve patient survival rates.
Area of Science:
- Neuro-oncology
- Drug Delivery Systems
- Cancer Therapeutics
Background:
- Glioblastoma is a highly malignant brain tumor with a poor prognosis.
- Current treatments are limited by resistance mechanisms, including DNA damage repair, glioma stem cells, and blood-brain barrier challenges.
- Systemic treatment toxicity also contributes to poor clinical outcomes.
Purpose of the Study:
- To explore innovative therapeutic strategies for glioblastoma.
- To investigate the potential of drug delivery systems combined with localized treatments.
- To identify effective combinatorial therapies targeting resistance mechanisms.
Main Methods:
- Review of preclinical and clinical research on glioblastoma treatment resistance.
- Analysis of the role of DNA damage repair pathways and glioma stem cells.
- Evaluation of drug delivery systems and alternative administration routes.
Main Results:
- Drug resistance is a major hurdle in glioblastoma treatment.
- Drug delivery systems and localized treatments show promise in overcoming resistance.
- Combinatorial therapies involving cytotoxic drugs and DNA damage response inhibitors are being explored.
Conclusions:
- Targeting DNA damage response pathways alongside advanced drug delivery systems is a promising avenue.
- Optimizing delivery approaches and administration routes is crucial for glioblastoma treatment innovation.
- Future research in these areas could significantly improve glioblastoma patient outcomes and quality of life.
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