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A Narrative Review  \nQuintino Giorgio D'Alessandris 1,2,†, Grazia Menna 1,†, Alessandro Izzo 2, Manuela D'Ercole 2, Giuseppe Maria Della Pepa 2, Liverana Lauretti 1,2, Roberto Pallini 1,2, Alessandro Olivi 1,2 and Nicola Montano 1,2, *  \nCitation: D'Alessandris, Q.G.;  \nMenna, G.; Izzo, A.; D'Ercole, M.; Della Pepa, G.M.; Lauretti, L.; Pallini, R.; Olivi, A.; Montano, N.  \nNeuromodulation for Brain Tumors: Myth or Reality? A Narrative Review.  \nInt. J. Mol. Sci. 2023, 24, 11738 . [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)ijms241411738  \nAcademic Editor: Lorenzo Corsi  \nReceived: 31 May 2023  \nRevised: 14 July 2023  \nAccepted: 17 July 2023  \nPublished: 21 July 2023  \nCopyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Department of Neuroscience, Universit Cattolica del Sacro Cuore, Largo F. Vito 1, 00168 Rome, Italy; [quintinogiorgio.dalessandris@policlinicogemelli.it](quintinogiorgio.dalessandris@policlinicogemelli.it) (Q.G.D.); [mennagrazia@gmail.com](mennagrazia@gmail.com) (G.M.); [liverana.lauretti@unicatt.it](liverana.lauretti@unicatt.it) (L.L.); [roberto.pallini@unicatt.it](roberto.pallini@unicatt.it) (R.P.); [alessandro.olivi@policlinicogemelli.it](alessandro.olivi@policlinicogemelli.it) (A.O.)  \n2 Department of Neurosurgery, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy; [alessandro.izzo@policlinicogemelli.it](alessandro.izzo@policlinicogemelli.it) (A.I.); [manuela.dercole@policlinicogemelli.it](manuela.dercole@policlinicogemelli.it) (M.D.); [giuseppemaria.dellapepa@policlinicogemelli.it](giuseppemaria.dellapepa@policlinicogemelli.it) (G.M.D.P.)  \n* [Correspondence: nicola.montano@policlinicogemelli.it](Correspondence: nicola.montano@policlinicogemelli.it)[ ](Correspondence: nicola.montano@policlinicogemelli.it)† These authors contributed equally to the work.  \nAbstract: In recent years, research on brain cancers has turned towards the study of the interplay between the tumor and its host, the normal brain. Starting from the establishment of a parallelism between neurogenesis and gliomagenesis, the influence of neuronal activity on the development of brain tumors, particularly gliomas, has been partially unveiled. Notably, direct electrochemical synapses between neurons and glioma cells have been identified, paving the way for new approaches for the cure of brain cancers. Since this novel field of study has been defined “cancer neuroscience”, anticancer therapeutic approaches exploiting these discoveries can be referred to as “cancer neuromodulation”. In the present review, we provide an up-to-date description of the novel findingsand of the therapeutic neuromodulation perspectives in cancer neuroscience. We focus both on more traditional oncologic approaches, aimed at modulating the major pathways involved in cancer neuroscience through drugs or genetic engineering techniques, and on electric stimulation proposals; the latter is at the cutting-edge of neuro-oncology.  \nKeywords: brain tumors; glioblastoma; neuromodulation; glutamate receptors; neuroligin-3; deep brain stimulation  \n1. Introduction  \nPrimary brain and central nervous system cancers represent a substantial source of morbidity and mortality worldwide. The most common and aggressive malignant primary brain tumors are represented by high-grade gliomas: over 12,000 new cases are diagnosed each year. The disease is characterized by systematic recurrence and limited progressionfree survival (PFS) . The burden of disease is compounded by the fact that, despite the giant strides made in the field, median survival r","cbCaildvorYUNJyh","https://ap.wps.com/l/cbCaildvorYUNJyh","pdf",287823,12,"English","# Introduction\n## Tumor–host interplay and cancer neuroscience\n## Neurogenesis–gliomagenesis parallelism\n## Neuronal activity, synapses, and neuromodulation concepts\n## Therapeutic perspectives: drugs, genetic engineering, and electric stimulation","[{\"question\":\"What is the central concept connecting neurogenesis and gliomagenesis in this review?\",\"answer\":\"The review describes a parallelism between neurogenesis and gliomagenesis and focuses on how neuronal activity can influence glioma development, including mechanisms linking tumor behavior to the host nervous system.\"},{\"question\":\"What discoveries enable the idea of “cancer neuromodulation”?\",\"answer\":\"Direct electrochemical synapses between neurons and glioma cells were identified. These findings support therapeutic strategies that exploit neural–tumor interactions, framed as cancer neuromodulation.\"},{\"question\":\"Which therapeutic directions are emphasized for brain tumors?\",\"answer\":\"The review highlights traditional oncologic approaches that modulate major cancer-neuroscience pathways using drugs or genetic engineering, as well as electric stimulation proposals described as cutting-edge in neuro-oncology.\"}]","Neuromodulation for Brain Tumors - Myth or Reality? - A Narrative Review | PDF",1790222861]