Repurposing Old Drugs: The Potential of an Anti-Psychotic in Brain Cancer Treatment

Recent research conducted by SAHMRI and Flinders University has unveiled promising insights into how a longstanding antipsychotic medication, trifluoperazine (TFP), could be a game-changer in treating glioblastoma (GBM), the most aggressive form of brain cancer. Historically used since the 1950s for schizophrenia and other psychiatric conditions, TFP is now showing potential beyond its original purpose.

Previous studies from Professor Cedric Bardy's Laboratory demonstrated TFP's ability to target and kill GBM cells effectively. The latest comprehensive review, published in Trends in Pharmacological Sciences, explores the mechanisms behind this effectiveness. Lead researcher Dr. Inushi De Silva explains that TFP interacts with dopamine receptors on GBM cells, disrupting critical pathways that enable tumor growth and adaptation.

Further, TFP impacts a transcription factor known as NUPR1, which has been linked to resistance against treatments like chemotherapy in GBM and other cancers such as pancreatic cancer. By targeting NUPR1, TFP could enhance the efficacy of current therapies like temozolomide, potentially overcoming treatment resistance.

Although TFP remains approved as an antipsychotic medication, its application as a cancer treatment has not been thoroughly explored. An earlier clinical trial in the 1990s investigated its effects on GBM but faced limitations due to design issues. Dr. De Silva emphasizes that the new findings could provide a foundation for future clinical trials, aiming to repurpose TFP as an adjunct therapy for brain cancer.

GBM's notorious ability to evade treatment by shifting between different cellular states makes it a challenging cancer to treat. According to Prof. Bardy, current therapies are insufficient, with median survival rates around 15 months. The multi-targeted action of TFP could inhibit this evasive behavior, making it a promising addition to existing treatment regimens.

The advantage of using an old, well-understood drug like TFP lies in its predictable side effect profile, which could facilitate quicker translation into clinical practice if efficacy is confirmed. Researchers are now seeking funding to initiate clinical trials to evaluate TFP’s role in brain cancer therapy.

In summary, this research highlights the potential of rethinking existing medications to address unmet needs in cancer treatment, offering hope for more effective management of glioblastoma in the future.