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The Neuro-Melanoma Singularity: Convergent Evolution of Neural and Melanocytic Networks in Brain Metastatic Adaptation. Biomolecules 2025, 15, 1683. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/biom15121683](10.3390/biom15121683)  \nCopyright: © 2025 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://creativecommons.org/](https://creativecommons.org/)[ ](https://creativecommons.org/)[licenses/by/4.0/](licenses/by/4.0/)) .  \n1 Faculty of General Medicine, Carol Davila University of Medicine and Pharmacy,  \n050474 Bucharest, Romania; [vladpetre.atanasescu@drd.umfcd.ro](vladpetre.atanasescu@drd.umfcd.ro) (V.-P.A.);  \nandreiiporosnicu@umfcd.ro (A.-L.P.); [cosmin.pantu@umfcd.ro](cosmin.pantu@umfcd.ro) (C.P.)  \n2 University Hospital, Faculty of Medicine (Faculty of General Medicine), Carol Davila University of Medicine and Pharmacy, 010024 Bucharest, Romania  \n3 Puls Med Association, 051885 Bucharest, Romania  \n4 Department of Anatomy, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania  \n5 Elias Emergency University Hospital, Faculty of Medicine (Faculty of General Medicine), Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania  \n6 Department of Neurosurgery, Carol Davila University of Medicine and Pharmacy,  \n050474 Bucharest, Romania  \n7 Department of Vascular Neurosurgery, National Institute of Neurology and Neurovascular Diseases,  \n077160 Bucharest, Romania  \n* Correspondence: [alexandru-valeriu.breazu@umfcd.ro](alexandru-valeriu.breazu@umfcd.ro) (A.B.); [stefan.oprea@umfcd.ro](stefan.oprea@umfcd.ro) (S.O.)† These authors contributed equally to this work.  \nAbstract  \nMelanoma 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–host 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–host 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–host coherence is developed as a function of the shar","cbCaia8sLgQa3gNR","https://ap.wps.com/l/cbCaia8sLgQa3gNR","pdf",1453739,34,"English","# Abstract\n# The Emergence of Neuro-Melanoma Convergence\n## Neural crest developmental memory in melanoma\n## CNS-specific microenvironment and reactivated programs\n## Endothelial contact, migration cues, and chemokine-directed signaling","[{\"question\":\"What enables melanoma cells to adapt after entering the brain?\",\"answer\":\"Melanoma cells reactivate dormant neural crest-derived migration and communication pathways and use vascular co-optation plus synaptic-function mimicry. These mechanisms support molecular, metabolic, and electrical similarity to neural circuitry and help sustain growth in the brain microenvironment.\"},{\"question\":\"How does the review explain the similarity between melanoma cells and neural tissue?\",\"answer\":\"The review attributes similarity to limited molecular, metabolic, and electrical overlap with brain circuitry. It emphasizes redox-coupled metabolic pathways and feedback-regulated signal transduction, along with vascular and synaptic mimicry to integrate into neural networks.\"},{\"question\":\"How does the proposed conceptual model relate therapy to tumor survival?\",\"answer\":\"The model treats therapies as selective disruptions of the neural, metabolic, and immunological couplings that enable metastatic adaptation. By breaking these couplings, therapeutic interventions can destabilize the tumor–host system sustaining coherence and persistence.\"}]","The Neuro-Melanoma Singularity - Convergent Evolution of Neural and Melanocytic Networks in Brain Metastatic Adaptation | PDF",1790219320,86]