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Neural Vulnerabilities in Glioblastoma: Rethinking Therapy Through Neuroactive Drug Repurposing.

Paola Onate Colobon¹, Sohyon Lee^1,2,3,4

¹Department of Biological Sciences, Korea Advanced Institute of Science & Technology (KAIST), Daejeon, Korea.

Brain Tumor Research and Treatment

|November 11, 2025

Summary

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.

Keywords:

Cancer neuroscience Drug repurposing Glioblastoma Neuroactive drugs

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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.