Drugs that are often targeted at nerve pain and seizures may provide new hope for patients with glioblastoma, the most aggressive form of brain cancer. According to a new study published in Natural Communications, patients receiving Gabapentin after surgical tumor resection have significantly longer survival advantages than those who did not receive the drug, with a survival advantage of 4-6 months, which coincides with the recent FDA-approved treatment for this devastating disease.
The study analyzed data from more than 1,000 patients with glioblastoma treated at major academic medical centers and found that gabapentin appears to work by disrupting communication between brain cancer cells and healthy neurons. This represents a potentially groundbreaking approach that targets the way tumors interact with their surroundings rather than directly attacking cancer cells.
But how do drugs commonly used for pain management ultimately fight the most drug-resistant cancers in medicine?
Brain tumors hijack normal neural connections
Latest findings in emerging fields of cancer neuroscience show that glioblastoma not only grows independently in the brain, but can also be actively integrated into neural circuits. According to researchers from the large-scale Brigham Young masses, these cancer cells establish a connection with normal neurons that naturally communicate with each other.
“In a 2023 report, our team showed that the level of functional connectivity between GBM and the normal brain negatively affects patients’ survival and cognition,” the researchers explained in the paper. Their work shows that areas of brain with higher functional connectivity to tumors contain cancer cells, which respond to neuronal activity in an enhanced manner.
These highly connected tumor cells secrete thrombocytopenin-1 (TSP-1), a protein that promotes synaptic formation and neural circuit remodeling. Earlier studies have shown that higher TSP-1 expression is associated with poor survival outcomes in patients with glioblastoma.
How gabapentin destroys cancer – Brain Connection
Gabapentin works by binding to the receptor of the TSP-1 target (the α2Δ subunit of the calcium channel, which is important for synaptic formation). By blocking this interaction, gabapentin can prevent cancer cells from building the neural connections they need to reproduce.
The team found that the survival rate of patients receiving gabapentin after tumor resection was significantly improved:
- In the main study group of 693 patients, the median survival of patients receiving gabapentin was 16 months, compared with 12 months.
- In the verification group of 379 patients from a separate institution, the median survival was 20.8 months, and gabapentin was not versus 14.7 months.
- Survival benefits remain significant even after controlling for factors such as age, tumor location and other treatments
- Patients receiving gabapentin had lower blood levels compared to matched controls
Turn painkillers into cancer treatment
Glioblastoma remains one of the most challenging cancers to treat, with about 12,000 new cases diagnosed each year in the United States. Standard treatment usually involves surgery, radiation, and chemotherapy, but even with active intervention, the median survival is only about 12-15 months.
The discovery of Gabapentin, a drug that has been widely prescribed for nerve pain and seizures, is particularly important. In the context, the field of tumor treatment is FDA-approved glioblastoma therapy, which also extends survival by about 6 months.
Although the current study is retrospective, this means that it analyzes data from patients who have been treated, rather than scheduledly assigning treatment, researchers will note key factors that may affect survival. They also validated their findings in two independent patient cohorts, enhancing the reliability of their results.
Going towards clinical application
The dose of gabapentin used in this study is relatively modest (495-600 mg per day) and is within the scope of common use for pain and seizure management. This suggests that repurposing drugs used for glioblastoma treatment may be relatively simple.
In addition, the researchers found preliminary evidence that gabapentin treatment reduces TSP-1 levels in patients’ blood samples. This finding suggests that TSP-1 has the potential to be used as a biomarker to determine which patients may benefit from Gabapentin therapy and to monitor treatment response.
“The findings that improve functional connectivity are associated with poor survival highlight the complex challenges that clinicians and surgeons face in glioma treatment. It requires a delicate balance between achieving maximum tumor resection and retaining “eloquent” brain regions to minimize neurological dysfunction, which can seriously affect the quality of life.”
Building on these promising results, clinical trials are now underway to anticipate the study of the effects of gabapentin and similar drugs in newly diagnosed patients with glioblastoma. These studies will provide more precise evidence on the efficacy of targeted neural links in brain cancer treatment.
For patients facing a glioblastoma diagnosis, the study offers new hope by revealing unexpected weapons in the fight against this aggressive disease. By repurposing established drugs with good safety, treatment progress may attract patients faster than brand new drugs that require years of development and testing.
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