A groundbreaking retrospective study conducted by researchers at Mass General Brigham has unveiled a promising correlation between the use of gabapentin—a widely prescribed anticonvulsant and neuropathic pain medication—and extended survival in patients suffering from glioblastoma (GBM), the deadliest and most common primary brain tumor in adults. Published recently in Nature Communications, this study reveals that gabapentinoids may hold therapeutic potential far beyond their traditional roles, potentially ushering in a new era of treatment strategies against this relentlessly fatal disease.
Glioblastoma, characterized by its aggressive invasiveness and rapid progression, persists as a formidable challenge in neuro-oncology. Despite decades of research, median survival rates linger stubbornly between 12 to 14 months post-diagnosis, and survival shrinks dramatically after tumor recurrence. The urgency to identify novel interventions is underscored by the tumor’s ability to infiltrate neural tissue and evade current therapeutic modalities. The Mass General Brigham team, led by neurosurgeon Dr. Joshua Bernstock, explored an unconventional hypothesis inspired by recent advances in cancer neuroscience that link tumor biology with neural activity.
This innovative approach traces its roots to an illuminating 2023 study published in Nature, which identified thrombospondin-1 (TSP-1) as a pivotal molecule facilitating the crosstalk between neurons and glioma cells. TSP-1, a matricellular protein implicated in synaptogenesis and neural plasticity, was shown to orchestrate a pro-tumorigenic microenvironment by modulating neural circuit remodeling in the vicinity of gliomas. Mouse models treated with gabapentin, known to antagonize the alpha2delta-1 subunit of voltage-gated calcium channels and attenuate TSP-1 mediated synaptogenic signaling, exhibited marked reduction in glioma progression. This insight provided the conceptual framework for evaluating gabapentin’s efficacy in human GBM patients retrospectively.
Analyzing clinical data from 693 patients diagnosed with GBM at Mass General Brigham, the researchers observed that those already receiving gabapentin for neuropathic pain symptoms demonstrated a statistically significant survival advantage. Specifically, patients on gabapentin lived an average of 16 months, a notable increase compared to the 12 months survival in their counterparts not prescribed the drug. This survival benefit, though modest in absolute terms, represents a critical incremental advance in the context of a disease with dismal prognosis and limited therapeutic options.
To corroborate these findings, Bernstock’s team collaborated with researchers at the University of California, San Francisco (UCSF), analyzing an independent cohort of 379 newly diagnosed GBM patients. Remarkably, this external dataset mirrored the initial observations, revealing gabapentin users survived on average 20.8 months, whereas non-users survived approximately 14.7 months. Pooling the data from both institutions, covering over 1,000 patients, solidified the statistical robustness of the survival benefit linked to gabapentinoid treatment in this context.
Intriguingly, the study also linked gabapentin use with reduced circulating levels of thrombospondin-1 in patients, suggesting that TSP-1 could serve as a biomarker for therapeutic response. However, the precise mechanistic interplay between gabapentin’s pharmacology, TSP-1 expression, and glioma biology remains to be fully elucidated. While preclinical models demonstrated that gabapentin interferes with TSP-1 mediated synaptic interactions that foster tumor growth, translating these molecular effects into clinical outcomes warrants further experimental and clinical scrutiny.
Dr. Bernstock highlighted the revolutionary nature of these findings, noting that the current GBM treatment paradigm, which relies heavily on surgical resection, radiation, and temozolomide chemotherapy, has seen minimal improvements in decades. The prospect that an already FDA-approved drug with an established safety profile might extend survival adds a compelling dimension to therapeutic strategies, emphasizing the importance of repurposing existing medications based on emerging biological insights.
Despite the hopeful data, the study’s retrospective design imposes limitations. Gabapentin was not administered within a controlled experimental framework aimed explicitly at treating glioblastoma; rather, its use was incidental, primarily for neuropathic symptom management. Consequently, confounding factors, patient selection biases, and treatment heterogeneity require cautious interpretation of results. The research team unequivocally calls for well-designed, prospective, randomized clinical trials to validate gabapentin’s efficacy in GBM and to dissect the underlying neurobiological mechanisms at play.
The interdisciplinary convergence of oncology, neuroscience, and pharmacology epitomized by this research underscores the paradigm shift toward understanding tumors not solely as isolated masses but as entities intricately intertwined with their neural microenvironment. The neuron–tumor axis represents an emerging frontier where targeting neural signaling pathways could disrupt tumor progression, offering fresh therapeutic avenues beyond traditional cytotoxic approaches.
Moreover, the identification of TSP-1 as a molecular mediator paves the way for biomarker-driven treatment personalization. If future studies confirm serum TSP-1 as a reliable indicator of gabapentin responsiveness or disease trajectory, clinicians may employ it to stratify patients and monitor therapeutic outcomes dynamically. Such precision medicine approaches are eagerly sought after in oncology, especially for malignancies as lethal and complex as glioblastoma.
This research offers a beacon of hope amid the relentless challenges posed by GBM. By repurposing a well-tolerated neuropharmacological agent, the study suggests modulation of tumor-neuron interactions can tangibly improve patient survival. As Dr. Bernstock rightfully emphasizes, embracing the evolving biological landscape and integrating neuroscience insights into oncology holds the promise of dismantling the long-standing therapeutic impasse in glioblastoma care.
In summary, the study by Bernstock et al. bridges preclinical discoveries with clinical retrospective data to highlight gabapentin’s potential as an adjunctive therapy conferring survival benefits in glioblastoma patients. While cautious optimism is warranted, the findings invigorate the neuro-oncology field, illuminating new paths for research and therapeutic innovation. The imperative now lies in translating this promising signal into clinical practice through rigorous trials and mechanistic investigations that may ultimately reshape the outlook for patients battling this devastating disease.
Subject of Research: People
Article Title: Gabapentinoids confer survival benefit in human glioblastoma
News Publication Date: 15-May-2025
Web References:
Mass General Brigham: https://www.massgeneralbrigham.org/
Nature Communications DOI: http://dx.doi.org/10.1038/s41467-025-59614-4
Nature study on TSP-1 and glioma: https://www.nature.com/articles/s41586-023-06036-1
References:
Bernstock, JD et al. “Gabapentinoids confer survival benefit in human glioblastoma.” Nature Communications, DOI: 10.1038/s41467-025-59614-4
Keywords: Glioblastomas, Cancer, Cancer research, Cancer treatments, Oncology
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