Gabapentinoids confer survival benefit in human glioblastoma
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.
Article Details
Authors (38)
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
Shawn L. Hervey-Jumper