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Neural Vulnerabilities in Glioblastoma: Rethinking Therapy Through Neuroactive Drug Repurposing
Paola Onate Colobon1, Sohyon Lee1,2,3,4
1Department of Biological Sciences, Korea Advanced Institute of Science & Technology (KAIST), Daejeon, Korea.
Abstract:
Glioblastoma, the most common and highly aggressive brain cancer, remains challenging to treat with limited gains in patient survival despite decades of research. Significant obstacles in developing new effective therapies for glioblastoma include the blood-brain barrier impeding drug delivery, inter- and intra-tumoral patient heterogeneity, and the lack of predictive preclinical models. Emerging insights from cancer neuroscience suggest that leveraging the neurodevelopmental and neurophysiological properties of glioblastoma may offer a new therapeutic window. In this context, neuroactive drugs (NADs) that are already approved for other central nervous system indications and can readily cross the blood-brain barrier may target these neural properties of glioblastoma through still unknown mechanisms. This review discusses existing preclinical models for glioblastoma drug discovery, explores how the tumor's neural-like behavior opens new therapeutic opportunities, and highlights the recent evidence supporting the repositioning of NADs as a paradigm shift in glioblastoma treatment.
Insights
Glioblastoma treatment faces challenges due to the blood-brain barrier and tumor heterogeneity. Repurposing neuroactive drugs (NADs) offers a promising new strategy by targeting the tumor's neural properties.
Area of Science:
- Neuro-oncology
- Cancer Neuroscience
- Pharmacology
Background:
- Glioblastoma is an aggressive brain cancer with limited treatment efficacy and survival gains.
- Key challenges include the blood-brain barrier, tumor heterogeneity, and inadequate preclinical models.
- Cancer neuroscience reveals glioblastoma's reliance on neurodevelopmental and neurophysiological processes.
Purpose of the Study:
- To review glioblastoma preclinical models for drug discovery.
- To explore therapeutic opportunities presented by the tumor's neural characteristics.
- To highlight the potential of repositioning neuroactive drugs (NADs) for glioblastoma treatment.
Main Methods:
- Literature review of existing glioblastoma preclinical models.
- Analysis of emerging evidence in cancer neuroscience.
- Examination of studies on neuroactive drug (NAD) repositioning.
Main Results:
- Preclinical models are crucial but often insufficient for glioblastoma drug discovery.
- Glioblastoma exhibits neural-like properties that can be therapeutically targeted.
- Neuroactive drugs (NADs) can cross the blood-brain barrier and may impact these neural properties.
Conclusions:
- Leveraging glioblastoma's neural properties presents a novel therapeutic avenue.
- Repositioning approved neuroactive drugs (NADs) is a promising paradigm shift for glioblastoma treatment.
- Further research is needed to elucidate the mechanisms of NADs in glioblastoma.
