Scientists at UCLA have discovered a potential new way to treat glioblastoma, the most aggressive type of brain cancer.
Their research, published in Proceedings of the National Academy of Sciences, shows that combining radiation therapy with forskolin, a compound derived from plants, can stop cancer cells from multiplying and spreading.
Glioblastoma is extremely difficult to treat because its cells grow uncontrollably and can survive even after surgery, chemotherapy, and radiation. A major challenge is glioma stem cells, which can regenerate tumors even after treatment.
The UCLA team found that radiation therapy temporarily makes glioblastoma cells more flexible, creating a window of opportunity to change their behavior. By adding forskolin at the right time, they were able to push these cancer cells into a dormant state—transforming them into neuron-like or microglia-like cells that do not divide uncontrollably.
“Unlike traditional therapies that just try to kill cancer cells, we use radiation to first make them more adaptable,” said Ling He, first author of the study. “Then, we guide them into becoming less harmful cell types.”
To test whether forskolin could reprogram glioblastoma cells, researchers conducted multiple experiments, including:
- Studying gene expression to track how cells changed
- Single-cell RNA sequencing to see how individual cancer cells transitioned into new types
- Testing glioma stem cells to see if forskolin reduced their ability to regrow tumors
- Using mouse models to see if the combined treatment improved survival
The results were promising. Forskolin was able to cross the blood-brain barrier and significantly reduce the number of glioma stem cells.
When tested in mice, the combination of radiation plus forskolin slowed tumor growth and extended survival:
- In aggressive glioblastoma, the median survival increased from 34 days to 48 days.
- In less aggressive tumors, survival increased from 43.5 days to 129 days—almost three times longer.
- Some mice experienced long-term tumor control, suggesting this approach could be highly effective.
Dr. Frank Pajonk, senior author of the study, explained the importance of these findings:
“By targeting the plasticity of glioblastoma cells, we are offering a new way to disrupt tumor growth and potentially extend patient survival.”
The researchers were also surprised to find that glioblastoma cells could switch into microglia-like cells—a type of immune cell found in the brain. Normally, these two cell types come from completely different developmental origins, but within the tumor environment, cancer cells appeared to change their identity.
This discovery opens up new possibilities for using glioblastoma’s adaptability against itself, potentially turning cancerous cells into cells that fight the tumor.
Next Steps: Can This Work in Humans?
Although this research is promising, it’s still in the early stages. The study focused on mice and lab-grown cells, so more testing is needed to determine if forskolin can be used safely and effectively in human patients.
The UCLA team is now working on:
- Refining the dosing strategy to improve long-term results
- Testing whether forskolin works with lower radiation doses
- Exploring clinical trials to see if this approach could be added to standard glioblastoma treatments
Glioblastoma has remained one of the hardest cancers to treat, with few new therapies in the past 20 years. By harnessing the temporary flexibility of cancer cells caused by radiation, forskolin offers a new way to fight this deadly disease.
“Our ultimate goal is to change how glioblastoma is treated,” said Pajonk. “This research could pave the way for therapies that don’t just destroy cancer cells, but transform them into something harmless.”
While further studies are needed, this breakthrough brings new hope for patients battling one of the most challenging brain cancers.
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The research findings can be found in PNAS.
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