Summary: A new study reveals that cerebrospinal fluid, which protects the brain, may be contributing to the resistance of brain cancers like glioblastoma to treatments. Exposure to this fluid causes tumor cells to change, making them resistant to radiation and common medications. However, researchers have found that an old anti-anxiety drug, trifluoperazine, shows promise in making these cells more receptive to therapies. This discovery could lead to the repurposing of the drug to improve survival rates in glioblastoma patients.
Key Facts:
- Exposure to cerebrospinal fluid causes glioblastoma cells to become more resistant to standard treatments.
- Trifluoperazine, a long-used anti-anxiety drug, can make these cancer cells more receptive to standard therapies without harming healthy brain cells.
- The research involved collaboration between neurobiologists, neurosurgeons, and oncologists, using tumor cells from 25 glioblastoma patients.
Source: Flinders University
A new research study shows that cerebrospinal fluid reduces current treatment efficacy in brain cancer and identifies new therapeutic opportunities.
Researchers from South Australia Health and Medical Research Institute (SAHMRI) and Flinders University have discovered that cerebrospinal fluid, the clear liquid that protects the brain, may be a factor in making brain cancers resistant to treatment. Their study, published in the journal Science Advances, also demonstrates that an old anti-anxiety drug can improve the effectiveness of chemo-radiotherapy for glioblastoma, the most common and lethal brain cancer.
Brain cancers are particularly deadly, especially among young individuals, and often do not respond well to current therapies. The research team speculates that unique brain features may play a role in this resistance.
For their study, the Australian researchers, comprising neurobiologists, neurosurgeons, and oncologists, collected tumor cells from 25 glioblastoma patients and exposed them to human cerebrospinal fluid. They found that the tumor cells quickly changed and became more resistant to radiation and temozolomide, a common drug used in glioblastoma therapy.
Associate Professor Cedric Bardy, the lead researcher, expressed the urgency of finding new treatments for glioblastoma. He stated, “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. 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.”
In investigating the molecular basis for these changes, the researchers discovered that glioblastoma cells exposed to cerebrospinal fluid were more resistant to a therapy-induced cell death known as ferroptosis. Importantly, they found that trifluoperazine, an anti-anxiety drug used since the 1950s, could re-sensitize glioblastoma cells to both radiation and temozolomide. Furthermore, trifluoperazine did not harm healthy brain cells. The researchers believe that combining trifluoperazine with standard care could potentially improve survival rates for glioblastoma patients.
About this brain cancer and neuropharmacology research news
Author: Tania Bawden
Source: Flinders University
Contact: Tania Bawden – Flinders University
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Human cerebrospinal fluid affects chemoradiotherapy sensitivities in tumor cells from patients with glioblastoma” by Cedric Bardy et al. Science Advances
Abstract
Human cerebrospinal fluid affects chemoradiotherapy sensitivities in tumor cells from patients with glioblastoma
Cancers in the central nervous system have shown resistance to therapies that are effective in other cancers, potentially due to the unique biochemistry of the human brain microenvironment composed of cerebrospinal fluid (CSF). However, the impact of CSF on cancer cells and therapeutic efficacy remains unknown.
This study examined the effect of human CSF on glioblastoma (GBM) tumors from 25 patients. The researchers found that CSF induces tumor cell plasticity and resistance to standard GBM treatments such as temozolomide and irradiation.
The researchers identified nuclear protein 1 (NUPR1), a transcription factor that hampers ferroptosis, as a mediator of therapeutic resistance in CSF. They found that inhibiting NUPR1 with trifluoperazine, a repurposed antipsychotic drug, enhanced the killing of GBM cells resistant to chemoradiation in CSF. Additionally, the researchers determined that the same chemo-effective doses of trifluoperazine were safe for human neurons and astrocytes derived from pluripotent stem cells.
These findings reveal that the efficacy of chemoradiotherapy decreases in the presence of human CSF and suggest that combining trifluoperazine with standard care has the potential to improve the survival of patients with GBM.
