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A new study shows that a decades-old anti-anxiety drug can improve the effectiveness of chemo-radiotherapy towards glioblastoma (GBM), the most common and lethal brain cancer.

The study, led by Associate Professor Cedric Bardy at SAHMRI and Flinders University and published in the journal Science Advances, indicates that cerebrospinal fluid could be a factor in making brain cancers resistant to treatment.

“Glioblastoma kills so many people who are otherwise fit, healthy and young, within months," A/Prof Bardy said.

"This is a horrible disease and the treatments available are just not effective enough despite serious side effects. This study helps us understand the limitations of the current chemotherapies and provides new hope for repurposing a class of drugs that could be added to the standard of care. We are working hard now to try this on patients in a clinical trial.”

The collaborative Australian team of neurobiologists, neurosurgeons and oncologists tested the effect of the precious resource of human cerebrospinal fluid on the growth of tumour cells collected from 25 local patients with GBM.

They found the tumour cells quickly changed their identity and became more resistant to radiation and the drug temozolomide, which are mainstays of GBM therapy.

Investigating the molecular basis for these changes, the team found GBM cells exposed to cerebrospinal fluid were more resistant to ferroptosis, a form of therapy-induced cell death.

Importantly, they showed that trifluoperazine, an anti-anxiety drug used since the 1950s, could re-sensitise GBM cells to both therapies. In contrast, trifluoperazine was found not to harm healthy brain cells. The researchers concluded that combining trifluoperazine with standard care could improve GBM patient survival.

Brain cancers kill more children and adults under 40 than any other cancer. They are resistant to therapies that kill cancers elsewhere in the body. The study team speculates that unique brain features might contribute to this.