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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.<\/jats:p>","DOI":"10.1038\/s41467-025-59614-4","type":"journal-article","created":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T05:02:17Z","timestamp":1747285337000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Gabapentinoids confer survival benefit in human glioblastoma"],"prefix":"10.1038","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7814-3867","authenticated-orcid":false,"given":"Joshua D.","family":"Bernstock","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mulki","family":"Mehari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakob V.","family":"E. 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Joshua D. Bernstock has an equity position in Treovir Inc. and UpFront Diagnostics. Dr. Bernstock is also a cofounder of Centile Bioscience and is on the NeuroX1 and QV Bioelectronics scientific advisory boards. Jason A. Chen is a cofounder and holds equity in Verge Genomics. Dr. Chen is also an advisor and holds equity in Gravity Medical Technology. Florian A. Gessler received honoraria from Signus, BBraun, Aesculap, and AstraZeneca. Gregory K. Friedman is supported by Eli Lilly and Company and Pfizer through contracts to UAB. Dr. Smith reports being a cofounder and equity holder of PheBe Health Inc.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"4483"}}