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In ALS, reduced ERBB4/HER4 activity characterizes ALS19, potentially driven by germline loss-of-function mutations and other mechanisms. Secreted NRG1 isoforms may further support ALS pathogenesis via glial stimulation, making pan-ERBB inhibitors plausible ALS candidates.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/neuregulin-1-and-als19-erbb4-at-the-crossroads-of-amyotrophic-lateral-sclerosis-and-cancer/338943/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/neuregulin-1-and-als19-erbb4-at-the-crossroads-of-amyotrophic-lateral-sclerosis-and-cancer/338943.png","ImageObject",300,407,{"name":42,"@type":43},"Patrick","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-30","2026-09-21",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",8,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"How does Neuregulin-1 (NRG1) relate to cancer and ALS?","Question",{"text":63,"@type":64},"NRG1 is involved in both cancer and neurologic diseases such as ALS. It can influence cell signaling through ERBB receptors, creating overlapping mechanistic pathways between oncology and neurology.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"What role do NRG1 fusions play in cancer?",{"text":68,"@type":64},"Some cancers harbor NRG1 fusions that upregulate NRG1 activity, increasing ERBB3/ERBB4 (HER3/HER4) receptor signaling and showing preliminary tissue-agnostic anti-cancer activity.",{"name":70,"@type":61,"acceptedAnswer":71},"Why is ERBB4/HER4 important in ALS19?",{"text":72,"@type":64},"In ALS, attenuated ERBB4/HER4 receptor activity is implicated, and ERBB4/HER4 is designated as ALS19. 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BMC Medicine (2024) 22:74 [https://doi.org/10.1186/s12916-024-03293-3](https://doi.org/10.1186/s12916-024-03293-3)  \nBMC Medicine  \n REVIEW Open Access  \nNeuregulin-1  \nand ALS19 (ERBB4):  \nat the crossroads of amyotrophic lateral sclerosis and cancer  \nJacob J. Adashek 1*†, Chinmayi Pandya2†, Nicholas J. Maragakis3, Pradip De4, Philip R. Cohen5,6, Shumei Kato2† and Razelle Kurzrock7,8,9*†  \nAbstract  \nBackground Neuregulin-1 (NRG1) is implicated in both cancer and neurologic diseases such as amyotrophic lateral sclerosis (ALS); however, to date, there has been little cross-field discussion between neurology and oncology in regard to these genes and their functions.  \nMain body Approximately 0.15–0. 5% of cancers harbor NRG1 fusions that upregulate NRG1 activity and hence that of the cognate ERBB3/ERBB4 (HER3/HER4) receptors; abrogating this activity with small molecule inhibitors/ antibodies shows preliminary tissue-agnostic anti-cancer activity. Notably, ERBB/HER pharmacologic suppression is devoid of neurologic toxicity. Even so, in ALS, attenuated ERBB4/HER4 receptor activity (due to loss-of-function germline mutations or other mechanisms in sporadic disease) is implicated; indeed, ERBB4/HER4 is designated ALS19 . Further, secreted-type NRG1 isoforms may be upregulated (perhaps via a feedback loop) and could contribute to ALS pathogenesis through aberrant glial cell stimulation via enhanced activity of other (e. g., ERBB1-3/HER1-3) receptors and downstream pathways. Hence, pan-ERBB inhibitors, already in use for cancer, may be agents worthy of testing in ALS.  \nConclusion Common signaling cascades between cancer and ALS may represent novel therapeutic targets for both diseases.  \nKeywords ALS19, Amyotrophic lateral sclerosis, Cancer, ERBB4, Novel targets, NRG1, Targeted therapy  \n†Jacob J. Adashek, Chinmayi Pandya, Shumei Kato and Razelle Kurzrock are contributed equally to this work.  \n*Correspondence:  \nJacob J. Adashek [jadashek@westernu.edu](jadashek@westernu.edu)[ ](jadashek@westernu.edu)Razelle Kurzrock  \nteoam201 [1@gmail.com](1@gmail.com)  \n1 Department of Oncology, The Johns Hopkins Hospital, The Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA  \n2 Center for Personalized Cancer Therapy and Division of Hematology and Oncology, Department of Medicine, UC San Diego Moores Cancer Center, La Jolla, CA, USA  \n3 Department of Neurology, The Johns Hopkins Hospital, Baltimore, MD, USA  \n4 Cancer Genomics, Avera Cancer Institute, Sioux Falls, SD, USA  \n5 Department of Dermatology, Davis Medical Center, University of California, Sacramento, CA, USA  \n6 Touro University California College of Osteopathic Medicine, Vallejo, CA, USA  \n7 WIN Consortium, Paris, France  \n8 MCW Cancer Center, Milwaukee, WI, USA  \n9 University of Nebraska, Omaha, NE, USA  \n© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/licenses/by/4.0/](http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ()[. The Creative Commons Public Domain Dedication waiver (](http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ()[http://creativecom](http://creativeco","cbCaihzoYzlkd7ZN","https://ap.wps.com/l/cbCaihzoYzlkd7ZN","pdf",2350954,13,"English","# Abstract\n## Background\n## Main body\n## Conclusion\n# Background\n## NRG1 signaling and receptor biology","[{\"question\":\"How does Neuregulin-1 (NRG1) relate to cancer and ALS?\",\"answer\":\"NRG1 is involved in both cancer and neurologic diseases such as ALS. It can influence cell signaling through ERBB receptors, creating overlapping mechanistic pathways between oncology and neurology.\"},{\"question\":\"What role do NRG1 fusions play in cancer?\",\"answer\":\"Some cancers harbor NRG1 fusions that upregulate NRG1 activity, increasing ERBB3/ERBB4 (HER3/HER4) receptor signaling and showing preliminary tissue-agnostic anti-cancer activity.\"},{\"question\":\"Why is ERBB4/HER4 important in ALS19?\",\"answer\":\"In ALS, attenuated ERBB4/HER4 receptor activity is implicated, and ERBB4/HER4 is designated as ALS19. This may result from loss-of-function germline mutations or other mechanisms in sporadic disease.\"}]","Neuregulin-1 and ALS19 (ERBB4) - at the Crossroads of Amyotrophic Lateral Sclerosis and Cancer | PDF",1790026669,33]