Patients with glioblastoma who took gabapentin—a widely prescribed medication for nerve pain and seizures—lived several months longer than those who didn't, according to a new study published in Nature Communications by research teams at Mass General Brigham and the University of California, San Francisco.
The retrospective analysis examined 693 glioblastoma patients treated at Mass General Brigham and found that those who received gabapentin had a median survival of 16 months—four months longer than the 12-month median survival for patients not taking the drug.
When researchers partnered with UCSF to analyze an additional 379 patients, they discovered an even more significant benefit: gabapentin-treated patients survived an average of 20.8 months compared to 14.7 months for those not receiving the medication.
"This study is an exciting step forward," said lead author Dr. Joshua Bernstock, a clinical fellow in neurosurgery at Brigham and Women's Hospital. "The discovery that an already approved medication with a favorable safety profile can extend overall survival represents a meaningful and potentially practice-changing advance."
Understanding the Biological Mechanism
The research was inspired by emerging insights from cancer neuroscience, which examines how tumors manipulate the nervous system to grow and survive. A 2023 study had shown that gliomas—a broad category of brain tumors that includes glioblastoma—integrate into neural circuits and use a protein called thrombospondin-1 (TSP-1) to fuel their growth.
Bernstock recognized that gabapentin was known to interfere with TSP-1 activity, creating a potential therapeutic opportunity using an existing medication rather than a novel experimental therapy.
"I looked at it three times the day it came out and said, 'Oh my God,'" Bernstock recalled. "This wasn't some novel experimental therapy. This was something already on the shelf, already being prescribed to patients."
The study also found that patients treated with gabapentin had lower levels of serum TSP-1, suggesting the protein may serve as an indicator of treatment response and supporting the proposed mechanism of action.
A Devastating Disease with Few Advances
Glioblastoma affects approximately 12,000 Americans annually and carries one of the bleakest prognoses in oncology. Despite decades of research, survival rates have barely improved, with most patients dying within 12 to 14 months of diagnosis.
The disease's resistance to chemotherapy and radiation, combined with its highly heterogeneous nature—meaning no two tumors are exactly alike, even within the same patient—has stalled progress and made breakthroughs rare.
"There have been very few advances in survival for GBM patients since the early 2000s," Bernstock noted. "We need to think more creatively about the emerging biology in these tumors and how to target them."
Moving Toward Clinical Trials
While the findings are promising, the researchers emphasize that only a randomized clinical trial can confirm gabapentin's true effect on glioblastoma survival. Bernstock's team controlled for as many confounding variables as possible in their retrospective analysis, but prospective studies are needed.
"We know it's biologically plausible," Bernstock said. "That, plus the drop in serum TSP-1, makes us think this is the probable mechanism."
Some early-stage recruitment for prospective trials is already underway, with researchers hoping the data will justify launching more comprehensive studies.
The Human Impact
For patients facing a glioblastoma diagnosis, even a few extra months of survival can be life-changing.
"You haven't seen these people in clinic," Bernstock said. "You've never had a father who wants to see his daughter graduate, or a mom who wants to help get the family's affairs in order before she passes."
These human stories drive researchers to continue searching for new approaches to this challenging disease. While gabapentin may not represent a cure, the potential to extend survival by several months using an already approved medication with a well-established safety profile could offer new hope to patients and their families while more definitive treatments are developed.
"This is just such a challenging disease," Bernstock concluded. "Gradual steps forward are going to be meaningful."
