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<p>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.</p>

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Gabapentinoids confer survival benefit in human glioblastoma

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年5月15日

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  • 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

摘要

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.