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Published on: March 28, 2021
Drug Repurposing, a Fast-Track Approach to Develop Effective Treatments for Glioblastoma
Ioannis Ntafoulis1, Stijn L W Koolen2,3, Sieger Leenstra1
1Brain Tumor Center, Department of Neurosurgery, Erasmus MC Cancer Institute, Erasmus University Medical Center, 3015 CN Rotterdam, The Netherlands.
Abstract:
Glioblastoma (GBM) remains one of the most difficult tumors to treat. The mean overall survival rate of 15 months and the 5-year survival rate of 5% have not significantly changed for almost 2 decades. Despite progress in understanding the pathophysiology of the disease, no new effective treatments to combine with radiation therapy after surgical tumor debulking have become available since the introduction of temozolomide in 1999. One of the main reasons for this is the scarcity of compounds that cross the blood-brain barrier (BBB) and reach the brain tumor tissue in therapeutically effective concentrations. In this review, we focus on the role of the BBB and its importance in developing brain tumor treatments. Moreover, we discuss drug repurposing, a drug discovery approach to identify potential effective candidates with optimal pharmacokinetic profiles for central nervous system (CNS) penetration and that allows rapid implementation in clinical trials. Additionally, we provide an overview of repurposed candidate drug currently being investigated in GBM at the preclinical and clinical levels. Finally, we highlight the importance of phase 0 trials to confirm tumor drug exposure and we discuss emerging drug delivery technologies as an alternative route to maximize therapeutic efficacy of repurposed candidate drug.
Insights
Glioblastoma treatment faces challenges due to the blood-brain barrier (BBB). This review explores drug repurposing and novel delivery methods to improve glioblastoma therapy and patient survival rates.
Area of Science:
- Neuro-oncology
- Pharmacology
- Drug Discovery
Background:
- Glioblastoma (GBM) has poor survival rates, with little improvement in treatment options for decades.
- The blood-brain barrier (BBB) significantly limits the efficacy of systemic therapies for brain tumors.
- Temozolomide, introduced in 1999, remains a primary treatment alongside radiation, highlighting the need for novel therapeutic strategies.
Purpose of the Study:
- To review the critical role of the BBB in developing effective glioblastoma treatments.
- To discuss drug repurposing as a strategy to identify CNS-penetrant drugs for GBM.
- To summarize current repurposed drug candidates and emerging delivery technologies for GBM therapy.
Main Methods:
- Literature review focusing on the BBB, drug repurposing, and glioblastoma therapeutics.
- Analysis of preclinical and clinical investigations of repurposed drugs for GBM.
- Discussion of phase 0 trials and advanced drug delivery systems.
Main Results:
- The BBB is a major obstacle, restricting therapeutic drug concentrations in brain tumors.
- Drug repurposing offers a viable approach to find candidates with favorable CNS penetration.
- Several repurposed drugs are under investigation, with emerging delivery technologies showing promise.
Conclusions:
- Overcoming the BBB is crucial for advancing glioblastoma treatment.
- Drug repurposing and innovative delivery methods are key strategies to improve therapeutic outcomes.
- Phase 0 trials are essential for validating drug exposure in brain tumors.
