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Current state and future perspective of drug repurposing in malignant glioma
Markus David Siegelin1, Elisabeth Schneider2, Mike-Andrew Westhoff3
1Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA.
Abstract:
Malignant gliomas are still extremely difficult to treat because complete surgical resection is biologically not feasible due to the invasive nature of these diseases and the proximity of tumors to functionally sensitive areas. Moreover, adjuvant therapies are facing a strong therapeutic resistance since the central nervous system is a highly protected environment and the tumor cells display a vast intra-tumoral genetic and epigenetic variation. As a consequence, new therapeutics are urgently needed but the process of developing novel compounds that finally reach clinical application is highly time-consuming and expensive. Drug repurposing is an approach to facilitate and accelerate the discovery of new cancer treatments. In malignant glioma, like in other cancers, pre-existing physiological pathways that regulate cell growth, cell death or cell migration are dysregulated causing malignant transformation. A wide variety of drugs are clinically used to treat non-cancerous diseases interfering with these malignancy-associated pathways. Repurposed drugs have key advantages: They already have approval for clinical use by national regulatory authorities. Moreover, they are for the most part inexpensive and their side effect and safety profiles are well characterized. In this work, we provide an overview on current repurposing strategies for the treatment of malignant glioma.
Insights
Drug repurposing offers a faster, cheaper way to find new treatments for malignant gliomas. This approach uses existing, approved drugs to target cancer pathways, overcoming therapeutic resistance.
Area of Science:
- Neuro-oncology
- Pharmacology
- Drug Discovery
Background:
- Malignant gliomas are challenging to treat due to invasive growth, proximity to critical brain areas, and resistance to therapies.
- The central nervous system's protected environment and tumor cell heterogeneity contribute to treatment failure.
- Developing novel therapeutics for malignant gliomas is a lengthy and costly process.
Purpose of the Study:
- To provide an overview of current drug repurposing strategies for malignant glioma treatment.
- To highlight the potential of repurposing existing drugs to accelerate cancer therapy development.
- To discuss the advantages of using approved drugs for novel cancer indications.
Main Methods:
- Review of current literature on drug repurposing in oncology, specifically for malignant glioma.
- Analysis of physiological pathways dysregulated in malignant glioma that can be targeted by existing drugs.
- Examination of the benefits and challenges of drug repurposing in clinical settings.
Main Results:
- Drug repurposing leverages existing drugs approved for other conditions, reducing development time and cost.
- Repurposed drugs often have well-characterized safety and side effect profiles.
- This approach targets key cancer pathways involved in cell growth, death, and migration.
Conclusions:
- Drug repurposing presents a viable and efficient strategy to accelerate the discovery of new treatments for malignant glioma.
- Utilizing approved drugs circumvents extensive preclinical and early clinical testing, offering a more cost-effective solution.
- This approach holds significant promise for overcoming therapeutic resistance and improving patient outcomes in malignant glioma.
