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Cancer cells release neurotrophic factors that support nerve-cell infiltration and create nerve–tumor crosstalk via neurotransmitters. This interaction can drive tumor proliferation, migration, and invasion, while tumor cells may form neuron-like networks. Neural-circuit players may act as biomarkers of aggressiveness and represent targets for anti-neurogenic inhibitors, though clinical efficacy needs further study. This review consolidates current knowledge and evaluates therapeutic potential.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/unveiling-the-neural-environment-in-cancer-exploring-the-role-of-neural-circuit-players-and-potential-therapeutic-strategies/377103/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/unveiling-the-neural-environment-in-cancer-exploring-the-role-of-neural-circuit-players-and-potential-therapeutic-strategies/377103.png","ImageObject",300,407,{"name":92,"@type":93},"นรินทร์","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-31","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":39},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why is the neural environment important in cancer progression?","Question",{"text":112,"@type":113},"The neural milieu around tumors is often overlooked, but it can be shaped by cancer cells that release factors enabling nerve infiltration. Through neurotransmitters, nerve–tumor crosstalk can promote proliferation, migration, and invasion.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What is neoneurogenesis and how does it relate to tumors?",{"text":117,"@type":113},"Neoneurogenesis refers to tumor-induced nerve growth in the tumor vicinity, enabled by releasing factors such as those associated with lymphangiogenesis and neoangiogenesis. Infiltrating nerve endings can then release neurotransmitters that support progression and metastasis.",{"name":119,"@type":110,"acceptedAnswer":120},"How can neural circuit players be used in cancer therapy?",{"text":121,"@type":113},"Expression levels of players in neural circuits may serve as biomarkers for cancer aggressiveness and correlate with poor prognosis in specific cancer types. Targeting these players with inhibitors is presented as a promising strategy, although the effectiveness of anti-neurogenic agents is still underexplored.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},377103,1791447782,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":39,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},2336475104957,"https://ap-avatar.wpscdn.com/avatar/22000c4c6bd8a5076e1?x-image-process=image/resize,m_fixed,w_180,h_180&k=1787554080175789136","cells  \nReview  \nUnveiling the Neural Environment in Cancer: Exploring the Role of Neural Circuit Players and Potential Therapeutic Strategies  \nTuan Minh Nguyen 1, Dinh Thi Minh Ngoc 1, Jung-Hye Choi 2, * and Chang-Hoon Lee 1, *  \nCitation: Nguyen, T.M.;  \nNgoc, D.T.M.; Choi, J.-H.; Lee, C.-H. Unveiling the Neural Environment in Cancer: Exploring the Role of Neural Circuit Players and Potential Therapeutic Strategies. Cells 2023, 12, 1996. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)cells12151996  \nAcademic Editors: Luisa Alexandra Meireles Pinto and Thorsten  \nR. Doeppner  \nReceived: 20 June 2023  \nRevised: 27 July 2023  \nAccepted: 1 August 2023  \nPublished: 3 August 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 College of Pharmacy, Dongguk University, Goyang 10326, Republic of Korea; [nmtuan28@dgu.ac.kr](nmtuan28@dgu.ac.kr) (T.M.N.); [minhngoc@dgu.ac.kr](minhngoc@dgu.ac.kr) (D.T.M.N.)  \n2 College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea  \n* [Correspondence: jchoi@khu.ac.kr](Correspondence: jchoi@khu.ac.kr) (J.-H.C.); [uatheone@dongguk.edu](uatheone@dongguk.edu) (C.-H.L.)  \nAbstract: The regulation of the immune environment within the tumor microenvironment has provided new opportunities for cancer treatment. However, an important microenvironment surrounding cancer that is often overlooked despite its significance in cancer progression is the neural environment surrounding the tumor. The release of neurotrophic factors from cancer cells is implicated in cancer growth and metastasis by facilitating the infiltration of nerve cells into the tumor microenvironment. This nerve–tumor interplay can elicit cancer cell proliferation, migration, and invasion in response to neurotransmitters. Moreover, it is possible that cancer cells could establish a network resembling that of neurons, allowing them to communicate with one another through neurotransmitters. The expression levels of players in the neural circuits of cancers could serve as potential biomarkers for cancer aggressiveness. Notably, the upregulation of certain players in the neural circuit has been linked to poor prognosis in specific cancer types such as breast cancer, pancreatic cancer, basal cell carcinoma, and stomach cancer. Targeting these players with inhibitors holds great potential for reducing the morbidity and mortality of these carcinomas. However, the efficacy of anti-neurogenic agents in cancer therapy remains underexplored, and further research is necessary to evaluate their effectiveness as a novel approach for cancer treatment. This review summarizes the current knowledge on the role of players in the neural circuits of cancers and the potential of anti-neurogenic agents for cancer therapy.  \nKeywords: neoneurogenesis; nerve–cancer crosstalk; prognosis; neurotransmitter  \n1. Introduction  \nThe tumor tissue of cancer patients is composed of cancer cells and the surrounding microenvironment of neighboring cells. Immunotherapies that regulate the immune milieu within the tumor ecosystem have paved the way for cancer treatment. They present an essential example of controlling the tumor microenvironment in anticancer therapy. However, one often overlooked microenvironment surrounding a cancer is the neural milieu surrounding the tumor.  \nTumors can stimulate nerve growth in their vicinity by releasing factors such as lymphangiogenesis and neoangiogenesis, a phenomenon known as neoneurogenesis. This neoneurogenesis may facilitate the development of new tumors, as nerve endings that infiltrate the tumor can release neurotransmitters that promote tumor progression and metastasis [1] . The ","cbCaircKKFZKnZYA","https://ap.wps.com/l/cbCaircKKFZKnZYA","pdf",3854309,27,"English","# Abstract\n# Introduction\n# Neurogenesis and Neoneurogenesis\n## Neurogenesis of Nerve Stem Cells (NSCs)","[{\"question\":\"Why is the neural environment important in cancer progression?\",\"answer\":\"The neural milieu around tumors is often overlooked, but it can be shaped by cancer cells that release factors enabling nerve infiltration. Through neurotransmitters, nerve–tumor crosstalk can promote proliferation, migration, and invasion.\"},{\"question\":\"What is neoneurogenesis and how does it relate to tumors?\",\"answer\":\"Neoneurogenesis refers to tumor-induced nerve growth in the tumor vicinity, enabled by releasing factors such as those associated with lymphangiogenesis and neoangiogenesis. Infiltrating nerve endings can then release neurotransmitters that support progression and metastasis.\"},{\"question\":\"How can neural circuit players be used in cancer therapy?\",\"answer\":\"Expression levels of players in neural circuits may serve as biomarkers for cancer aggressiveness and correlate with poor prognosis in specific cancer types. Targeting these players with inhibitors is presented as a promising strategy, although the effectiveness of anti-neurogenic agents is still underexplored.\"}]","Unveiling the Neural Environment in Cancer - Exploring the Role of Neural Circuit Players and Potential Therapeutic Strategies | PDF",1790223196,68]