Glioblastoma, the deadliest form of brain cancer, presents a formidable challenge with a median survival time of 15 to 18 months. Standard treatments, including surgery, chemotherapy, and radiation, have remained largely unchanged for two decades. However, a recent study offers a glimmer of hope, unveiling a potential new therapy with a unique approach to combatting this aggressive cancer.
Researchers in Los Angeles have developed a novel strategy to force glioblastoma cells into a harmless, non-dividing state. This innovative approach combines traditional radiation therapy with forskolin, a natural product derived from a plant related to mint. Published in the journal PNAS, the study details how this combination extended the lifespan of laboratory mice with glioblastoma, suggesting a potential pathway for future human treatment.
Glioblastoma’s aggressiveness stems from the uncontrolled division of its cancer cells, which can resist treatment and recur after therapy. The blood-brain barrier, a protective membrane separating blood from cerebrospinal fluid, further complicates treatment by hindering the effectiveness of cancer therapies. However, previous research indicates that radiation, while eliminating some glioblastoma cells, also temporarily renders glioma stem cells—a type of glioblastoma cell linked to tumor growth and treatment resistance—more susceptible to change.
“Radiation therapy, while effective in killing many cancer cells, also induces a temporary state of cellular flexibility,” explains Dr. Frank Pajonk, an oncologist at the University of California, Los Angeles (UCLA) and senior author of the study. “We found a way to exploit this flexibility by using forskolin to push these cells into a nondividing, neuron-like or microglia-like state.” Microglia are immune cells within the central nervous system.
The researchers focused on forskolin due to its known ability to promote cell maturation, the process by which unspecialized cells develop into their mature, specialized forms, specifically into neurons. The observed transformation of glioblastoma cells into neuron-like cells was unexpected, considering the distinct origins and functions of these cell types. This adaptation appears to be facilitated by the unique microenvironment of the tumor.
“Our approach is unique because it leverages the timing and effects of radiation,” explains Dr. Ling He, a UCLA oncologist and first author of the study. “Unlike traditional therapies that force cancer cells to mature, we use radiation to create a temporary, flexible state, making glioma cells easier to guide into specialized, less harmful types. By adding forskolin at the right moment, we push these cells to become neuron-like or microglia-like, reducing their potential to regrow into tumors.” This is significant because neurons, unlike cancer cells, do not continuously divide.
When tested on mice with glioblastoma, the combination of radiation and forskolin demonstrated promising results. Forskolin successfully crossed the blood-brain barrier and significantly slowed tumor growth. In mice with a highly aggressive form of glioblastoma, the combined therapy increased the median survival time from 34 days with radiation alone to 48 days. In mice with a less aggressive form, the median survival time dramatically increased from 43.5 days to 129 days. Remarkably, some mice even achieved long-term tumor control.
While some mice experienced tumor recurrence, underscoring the need for further research, the findings suggest a potential new avenue for glioblastoma treatment. Dr. Pajonk concludes, “this research offers a promising strategy to disrupt tumor progression and enhance patient survival.” This innovative approach warrants further investigation to explore its full potential in combating this devastating disease.
