Gabapentin Shows Unexpected Survival Boost in Brain Cancer Patients todayheadline

A medication commonly prescribed for nerve pain and seizures may offer new hope for patients with glioblastoma, the most aggressive form of brain cancer. According to a new study published in Nature Communications, patients who received gabapentin after surgical tumor removal lived significantly longer than those who didn’t receive the drug, with a survival advantage of 4-6 months—comparable to the benefit seen with the most recently FDA-approved treatment for this devastating disease.

The study analyzed data from over 1,000 glioblastoma patients treated at major academic medical centers, finding that gabapentin appears to work by interrupting communication between brain cancer cells and healthy neurons. This represents a potentially groundbreaking approach that targets the way tumors interact with their surrounding environment rather than attacking the cancer cells directly.

But how does a medication typically used for pain management end up fighting one of medicine’s most treatment-resistant cancers?

Brain Tumors Hijack Normal Neural Connections

Recent discoveries in the emerging field of cancer neuroscience have revealed that glioblastomas don’t just grow independently within the brain—they actively integrate into neural circuits. According to the investigators from Mass General Brigham, these cancer cells establish connections with normal neurons similar to how brain cells naturally communicate with each other.

“In a report from 2023, our team demonstrated that the degree of functional connectivity between GBM and the normal brain negatively affected patient survival and cognition,” the researchers explain in their paper. Their work showed that brain regions with higher functional connectivity to tumors contained cancer cells with heightened responsiveness to neuronal activity.

These highly connected tumor cells secrete thrombospondin-1 (TSP-1), a protein that promotes synapse formation and neural circuit remodeling. Earlier research suggested that higher TSP-1 expression correlates with worse survival outcomes in glioblastoma patients.

How Gabapentin Disrupts the Cancer-Brain Connection

Gabapentin works by binding to the same receptor that TSP-1 targets—the α2δ subunit of calcium channels that are important for synapse formation. By blocking this interaction, gabapentin may prevent cancer cells from establishing the neural connections they need to thrive.

The research team found that patients who received gabapentin after tumor removal showed significantly improved survival rates:

• In the primary study group of 693 patients, median survival was 16 months for patients who received gabapentin versus 12 months for those who didn’t
• In the validation group of 379 patients from a separate institution, median survival was 20.8 months with gabapentin versus 14.7 months without
• The survival benefit remained significant even after controlling for factors like age, tumor location, and other treatments
• Patients receiving gabapentin had lower levels of TSP-1 in their blood compared to matched controls

Turning Pain Medication into Cancer Treatment

Glioblastoma remains one of the most challenging cancers to treat, with approximately 12,000 new cases diagnosed annually in the United States. Standard treatment typically includes surgery, radiation, and chemotherapy, but even with aggressive intervention, median survival is only about 12-15 months.

The finding that gabapentin—a medication already widely prescribed for nerve pain and seizures—could extend survival by several months is particularly important. For context, tumor-treating fields, the most recent FDA-approved therapy for glioblastoma, also extends survival by roughly 6 months.

While the current study was retrospective, meaning it analyzed data from patients who had already been treated rather than assigning treatments prospectively, the researchers took care to account for key factors that could influence survival. They also validated their findings across two independent patient cohorts, strengthening the reliability of their results.

Moving Toward Clinical Applications

The gabapentin doses used in the study were relatively modest—a median of 495-600 mg daily—and fall within the range commonly prescribed for pain and seizure management. This suggests that repurposing the drug for glioblastoma treatment could be relatively straightforward.

Additionally, the researchers found preliminary evidence that gabapentin treatment reduced TSP-1 levels in patient blood samples. This finding suggests that TSP-1 could potentially serve as a biomarker to identify which patients might benefit most from gabapentin therapy and to monitor treatment response.

“The finding that increased functional connectivity is associated with worse survival underscores the complex challenge clinicians and surgeons face in glioma treatment. It requires a delicate balance between achieving maximal tumor resection and preserving ‘eloquent’ brain regions to minimize neurologic deficits, which can severely affect quality of life,” the researchers note.

Building on these promising results, clinical trials are now underway to prospectively investigate the effects of gabapentin and similar drugs in newly diagnosed glioblastoma patients. These studies will provide more definitive evidence about the efficacy of targeting neural connections in brain cancer treatment.

For patients facing a glioblastoma diagnosis, this research offers new hope by revealing an unexpected weapon in the fight against this aggressive disease. By repurposing an established medication with a well-understood safety profile, treatment advances could potentially reach patients more quickly than entirely new drugs that require years of development and testing.