Breakthrough in Glioblastoma: Repurposed Neuroactive Drugs Show Promising Anti-Cancer Potential

SciFocus/Oct 29, 2024 -- Glioblastoma, the most aggressive form of brain cancer, has long defied treatment innovations, relying primarily on DNA-alkylating chemotherapies that offer limited survival benefits. A pioneering study published in Nature Medicine (2024) reveals a new, promising approach, utilizing high-throughput screenings of neuroactive drugs to target glioblastoma’s neural mechanisms, offering a lifeline for potential treatment advancements.

"Using pharmacoscopy & in-silico drug MoA discovery, we show that the antidepressant vortioxetine is effective in glioblastoma primary patient material and in mouse models." — Dr. Berend Snijder, study corresponding author

Key Highlights:

- Extensive Screening: Researchers profiled 2,500 drug responses across 27 glioblastoma patients, using single-cell analysis to assess the impact of neuroactive drugs on cancer cells.

- Neuroactive Drugs: The study identified diverse neuroactive compounds with anti-cancer efficacy, highlighting vortioxetine, an antidepressant, as a potent candidate when combined with standard chemotherapies.

- Molecular Insights: Machine learning of drug-target networks pinpointed the AP-1/BTG pathway as a vulnerability in glioblastoma, triggered by calcium-driven neural signaling.

- Broad Validation: Vortioxetine’s effect was validated across multiple model systems, showing significant anti-cancer responses in 75% of tested patients.

- Future Implications: These findings lay the groundwork for clinical trials exploring vortioxetine in combination with traditional therapies, with potential for tailored, patient-specific glioblastoma treatments.

This landmark study provides a framework for treating glioblastoma based on its neural roots, with vortioxetine emerging as a key candidate. By tapping into neurodevelopmental vulnerabilities, researchers have opened new pathways for personalized, effective glioblastoma therapy. The integration of neuroactive drugs could soon transform glioblastoma treatment and improve outcomes for patients facing this challenging disease.

Source: https://www.nature.com/articles/s41591-024-03224-y

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