Gabapentinoids confer survival benefit in human glioblastoma

Joshua D. Bernstock (), Mulki Mehari, Jakob V. E. Gerstl, David M. Meredith, Pablo A. Valdes, Philip Heesen, Vardhaan S. Ambati, Saritha Krishna, Jason A. Chen, Harshit Arora, Benjamin R. Johnston, Mikias Negussie, Kristina Grieco, Cesar Nava Gonzales, Abraham Dada, Anna B. Lebouille-Veldman, Aymen Kabir, Lennard Spanehl, Jasleen Kaur, Sena Oten, Youssef E. Sibih, Rania A. Mekary, Andy Daniel, John Frederick de Groot, Saef Izzy, Florian A. Gessler, Scellig Stone, Omar Arnaout, Yi Lu, Bryan D. Choi, Matthew D. Hall, Minesh P. Mehta, Yazmin Odia, Gregory K. Friedman, E. A. Chiocca, Pier Paolo Peruzzi, Timothy R. Smith and Shawn L. Hervey-Jumper ()
Additional contact information
Joshua D. Bernstock: Harvard Medical School
Mulki Mehari: University of California San Francisco
Jakob V. E. Gerstl: Harvard Medical School
David M. Meredith: Harvard Medical School
Pablo A. Valdes: University of Texas Medical Branch
Philip Heesen: Harvard Medical School
Vardhaan S. Ambati: University of California San Francisco
Saritha Krishna: University of California San Francisco
Jason A. Chen: Harvard Medical School
Harshit Arora: Harvard Medical School
Benjamin R. Johnston: Harvard Medical School
Mikias Negussie: University of California San Francisco
Kristina Grieco: Harvard Medical School
Cesar Nava Gonzales: University of California San Francisco
Abraham Dada: University of California San Francisco
Anna B. Lebouille-Veldman: Harvard Medical School
Aymen Kabir: University of California San Francisco
Lennard Spanehl: Harvard Medical School
Jasleen Kaur: University of California San Francisco
Sena Oten: University of California San Francisco
Youssef E. Sibih: University of California San Francisco
Rania A. Mekary: Harvard Medical School
Andy Daniel: University of California San Francisco
John Frederick de Groot: University of California San Francisco
Saef Izzy: Harvard Medical School
Florian A. Gessler: Rostock University Medical Center
Scellig Stone: Harvard Medical School
Omar Arnaout: Harvard Medical School
Yi Lu: Harvard Medical School
Bryan D. Choi: Harvard Medical School
Matthew D. Hall: Baptist Health South Florida
Minesh P. Mehta: Florida International University
Yazmin Odia: Baptist Health South Florida
Gregory K. Friedman: The University of Texas MD Anderson Cancer Center
E. A. Chiocca: Harvard Medical School
Pier Paolo Peruzzi: Harvard Medical School
Timothy R. Smith: Harvard Medical School
Shawn L. Hervey-Jumper: University of California San Francisco

Nature Communications, 2025, vol. 16, issue 1, 1-6

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-59614-4

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