A decades-old anti-anxiety drug can help improve the effectiveness of chemo-radiotherapy towards glioblastoma (GBM) the most common and lethal brain cancer.Brain cancers kill more children and adults under 40 than any other cancer. They are resistant to therapies that kill cancer elsewhere in the body.
The study, published in the journal Science Advances, found cerebrospinal fluid -- the clear colourless liquid that protects the brain reduces current treatment efficacy in brain cancer. It also may be a factor that makes brain cancers resistant to treatment, said researchers from Flinders University in Australia.
The study team tested the effect of the precious resource of human cerebrospinal fluid on the growth of tumour cells collected from 25 local patients with glioblastoma.Among their findings, the tumour cells quickly changed their identity and became more resistant to radiation and the drug temozolomide, which are mainstays of glioblastoma therapy.
"Glioblastoma kills so many people who are otherwise fit, healthy and young, within months. This is a horrible disease, and the treatments available are just not effective enough despite serious side effects,” said Cedric Bardy, Associate Professor at Flinders.
"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."
Investigating the molecular basis for these changes, the team found glioblastoma 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 glioblastoma cells to both therapies.
In contrast, trifluoperazine was found not to harm healthy brain cells. The researchers concluded that combining trifluoperazine with standard care may improve GBM patient survival.