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60-year-old drug can resensitize treatment-resistant brain cancer cells

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60-year-old drug can resensitize treatment-resistant brain cancer cells

Researchers have discovered that cerebrospinal fluid, the brain’s shock absorber, contributes to treatment resistance in people with brain cancer. But their study also identified a more-than-sixty-year-old antipsychotic medication that can be repurposed to resensitize cancer cells to treatment.

Cerebrospinal fluid (CSF) has several important functions. It acts like a cushion to protect the brain and spinal cord and provides nourishment and waste removal services. But, when it comes to brain cancer, a new study has found that this important fluid may be making brain cancers resistant to treatment, reducing their effectiveness.

Researchers from Flinders University in South Australia examined the effect of CSF on the growth of tumor cells in patients with glioblastoma, a common, fast-growing and lethal central nervous system cancer, and, importantly, discovered a potential treatment.

“Glioblastoma kills so many people who are otherwise fit, healthy and young, within months,” said Cedric Bardy, one of the study’s co-authors. “This is a horrible disease, and the treatments available are just not effective enough despite serious side effects.”

The mainstay treatments for glioblastoma are surgical resection, followed by a combination of radiation therapy and the oral chemotherapeutic drug temozolomide. Despite this aggressive treatment, the cancer often returns and proves fatal, indicating that the cancer cells have developed a resistance to treatment.

Taking CSF from 25 patients with glioblastoma receiving both radiation and chemotherapy, the researchers found that cancer cells exposed to CSF were more resistant to ferroptosis, a form of therapy-induced cell death. They identified that nuclear protein 1 (NUPR1) in the CSF was responsible for increasing treatment resistance by hampering ferroptosis.

Importantly, they found that trifluoperazine, a drug that’s been marketed as an antipsychotic and anti-anxiety medication since 1959 under the brand name Stelazine, inhibited NUPR1 and resensitized the cancer cells to both therapies. The researchers concluded that adding trifluoperazine to current treatments may improve GBM survival rates.

“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,” Bardy said. “We are working hard now to try this on patients in a clinical trial.”

The study was published in the journal Science Advances.

Source: Flinders University

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