{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T15:21:54Z","timestamp":1787498514586,"version":"build-2736575974"},"reference-count":197,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T00:00:00Z","timestamp":1764633600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Medicine and Pharmacy Carol Davila"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Melanoma cells in the brain may use similar mechanisms for adapting to injury and\/or disease (that is, through continued reallocation of energy, matter, and information) as other cell types do to create an environment in which cancer cells can grow and sustain themselves within the confines of the brain. These adaptable mechanisms include the ability to reactivate dormant neural crest-derived migration and communication pathways. Unlike some other types of cancers that invade neural tissue as a simple invasion, melanomas are capable of achieving limited molecular, metabolic, and electrical similarity to the neural circuitry of the brain. Melanomas achieve this limited similarity through both vascular co-optation and mimicking synaptic functions, as well as through their engagement of redox-coupled metabolic pathways and feedback-regulated signal transduction pathways. The result is the creation of a metastable tumor\u2013host system, where the relationship between tumor and host is defined by the interaction of stabilizing and destabilizing forces; forces that define the degree of coherence, vulnerability, and persistence of the tumor\u2013host system. In this review, we integrate molecular, electrophysiological, and anatomical data to develop a single unifying hypothesis for the functional integration of melanoma cells into the neural tissue of the brain. Additionally, we describe how neural crest-based regulatory pathways are reactivated in the adult brain and how tumor\u2013host coherence is developed as a function of the shared thermodynamic and informational constraints placed on both tumor and host. We also describe how our proposed conceptual model allows for the understanding of therapeutic interventions as selective disruptions of the neural, metabolic, and immunological couplings that support metastatic adaptation.<\/jats:p>","DOI":"10.3390\/biom15121683","type":"journal-article","created":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T12:39:43Z","timestamp":1764679183000},"page":"1683","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The Neuro-Melanoma Singularity: Convergent Evolution of Neural and Melanocytic Networks in Brain Metastatic Adaptation"],"prefix":"10.3390","volume":"15","author":[{"given":"Vlad-Petre","family":"Atanasescu","sequence":"first","affiliation":[{"name":"Faculty of General Medicine, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"},{"name":"University Hospital, Faculty of Medicine (Faculty of General Medicine), \u201cCarol Davila\u201d University of Medicine and Pharmacy, 010024 Bucharest, Romania"},{"name":"Puls Med Association, 051885 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandru","family":"Breazu","sequence":"additional","affiliation":[{"name":"Faculty of General Medicine, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"},{"name":"Puls Med Association, 051885 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6296-8364","authenticated-orcid":false,"given":"Stefan","family":"Oprea","sequence":"additional","affiliation":[{"name":"Faculty of General Medicine, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"},{"name":"Puls Med Association, 051885 Bucharest, Romania"},{"name":"Department of Anatomy, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrei-Ludovic","family":"Porosnicu","sequence":"additional","affiliation":[{"name":"Faculty of General Medicine, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"},{"name":"Puls Med Association, 051885 Bucharest, Romania"},{"name":"Elias Emergency University Hospital, Faculty of Medicine (Faculty of General Medicine), Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anamaria","family":"Oproiu","sequence":"additional","affiliation":[{"name":"Faculty of General Medicine, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"},{"name":"University Hospital, Faculty of Medicine (Faculty of General Medicine), \u201cCarol Davila\u201d University of Medicine and Pharmacy, 010024 Bucharest, Romania"},{"name":"Puls Med Association, 051885 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mugurel-Petrinel","family":"R\u0103doi","sequence":"additional","affiliation":[{"name":"Faculty of General Medicine, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"},{"name":"Puls Med Association, 051885 Bucharest, Romania"},{"name":"Department of Neurosurgery, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"},{"name":"Department of Vascular Neurosurgery, National Institute of Neurology and Neurovascular Diseases, 077160 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Octavian","family":"Munteanu","sequence":"additional","affiliation":[{"name":"Faculty of General Medicine, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"},{"name":"University Hospital, Faculty of Medicine (Faculty of General Medicine), \u201cCarol Davila\u201d University of Medicine and Pharmacy, 010024 Bucharest, Romania"},{"name":"Puls Med Association, 051885 Bucharest, Romania"},{"name":"Department of Anatomy, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9043-3690","authenticated-orcid":false,"given":"Cosmin","family":"Pantu","sequence":"additional","affiliation":[{"name":"Faculty of General Medicine, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"},{"name":"Puls Med Association, 051885 Bucharest, Romania"},{"name":"Department of Anatomy, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Rice, R., Cebra-Thomas, J., Haugas, M., Partanen, J., Rice, D.P.C., and Gilbert, S.F. 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