Gabapentinoids confer survival benefit in human glioblastoma

Neuronal-glioma interactions are increasingly recognized as critical in the development and progression of central nervous system tumors. Recent research highlights that gliomas can integrate into neural circuits through various mechanisms, including the synaptogenic factor thrombospondin-1 (TSP-1). This new mechanistic understanding of cancer neuroscience allows for novel insights into target discovery. Critically, therapies that modulate neuron-tumor interactions remain agnostic to other oncogenic changes within tumor cells yet may still target fundamental drivers of tumor growth. In line with these findings and controlling for critical confounding variables, we demonstrate a survival benefit associated with gabapentin (an antagonist of TSP-1) following surgical resection of newly diagnosed glioblastoma. This retrospective, multi-institutional cohort study included 1,072 patients, with a discovery cohort of 693 patients and an additional 379 patients from a separate site for external validation. Furthermore, our findings indicate that gabapentin administration is associated with reduced serum TSP-1 levels, suggesting its potential as a future biomarker.

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Publication Details

Journal
Nature Communications
Published
2025-05-15
DOI
https://doi.org/10.1038/s41467-025-59614-4
Citations
12
Primary Topic
Glioma Diagnosis and Treatment
Type
article
Field-Weighted Citation Impact
19.50

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article

Gabapentinoids confer survival benefit in human glioblastoma

Saritha Krishna, Benjamin Johnston, Joshua D. Bernstock, Pierpaolo Peruzzi et al.
12 citations
Nature Communications
Glioma Diagnosis and Treatment
19.50
article

Gabapentinoids confer survival benefit in human glioblastoma

Saritha Krishna, Benjamin Johnston, Joshua D. Bernstock, Pierpaolo Peruzzi, Jakob V. E. Gerstl, Cesar Nava Gonzales, Timothy R. Smith, Philip Heesen, E. Antonio Chiocca, Rania A. Mekary, Pablo A. Valdés, Kristina Grieco, Scellig S. D. Stone, Anna B. Lebouille-Veldman, Yazmín Odia, Shawn L. Hervey‐Jumper, Minesh P. Mehta, Bryan D. Choi, Omar Arnaout, Mulki Mehari, David M. Meredith, Harshit Arora, Lennard Spanehl, Mikias Negussie, John de Groot, Andy Daniel, Saef Izzy, Matthew D. Hall, Florian Geßler, Jasleen Kaur, Yi Lu, Vardhaan Sai Ambati, Gregory K. Friedman, Youssef Sibih, Sena Oten, Jason Chen, Abraham Dada, Aymen Kabir
article en
12 citations

Abstract

Neuronal-glioma interactions are increasingly recognized as critical in the development and progression of central nervous system tumors. Recent research highlights that gliomas can integrate into neural circuits through various mechanisms, including the synaptogenic factor thrombospondin-1 (TSP-1). This new mechanistic understanding of cancer neuroscience allows for novel insights into target discovery. Critically, therapies that modulate neuron-tumor interactions remain agnostic to other oncogenic changes within tumor cells yet may still target fundamental drivers of tumor growth. In line with these findings and controlling for critical confounding variables, we demonstrate a survival benefit associated with gabapentin (an antagonist of TSP-1) following surgical resection of newly diagnosed glioblastoma. This retrospective, multi-institutional cohort study included 1,072 patients, with a discovery cohort of 693 patients and an additional 379 patients from a separate site for external validation. Furthermore, our findings indicate that gabapentin administration is associated with reduced serum TSP-1 levels, suggesting its potential as a future biomarker.

Nature CommunicationsVol. 16(1)
Brigham and Women's Hospital (US), Boston Children's Hospital (US), Baptist Hospital of Miami (US), The University of Texas MD Anderson Cancer Center (US), Harvard University (US), Massachusetts College of Pharmacy and Health Sciences (US), University of California, San Francisco (US), Florida International University (US), Massachusetts General Hospital (US), Baptist Health South Florida (US), Neurological Surgery (US), University of Rostock (DE), The University of Texas Medical Branch at Galveston (US), Massachusetts Institute of Technology (US)
Deutsche Forschungsgemeinschaft
Good health and well-being
Openalex Percentile: Top 0%
Glioma Diagnosis and Treatment
19.50
DOIOpen Access PDFOpenAlex
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