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Differentiation-based therapy is presented as a promising strategy for this disease. The study shows that the CDK4/6 inhibitor palbociclib drives extensive neuronal differentiation of adrenergic neuroblastoma cells, accompanied by phenotypic and transcriptional changes and an epigenetic program. In vivo, palbociclib suppresses tumor growth in mouse models.",{"@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/palbociclib-releases-the-latent-differentiation-capacity-of-neuroblastoma-cells/447665/",{"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/palbociclib-releases-the-latent-differentiation-capacity-of-neuroblastoma-cells/447665.png","ImageObject",300,407,{"name":92,"@type":93},"pixelkiddo","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":52},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What problem does this work address in neuroblastoma?","Question",{"text":112,"@type":113},"Neuroblastoma tumors fail to differentiate and remain in an immature state that drives tumor growth.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What role does palbociclib play in the study?",{"text":117,"@type":113},"Palbociclib inhibits proliferation and induces extensive neuronal differentiation, along with phenotypic, transcriptional, and epigenetic program changes.",{"name":119,"@type":110,"acceptedAnswer":120},"How does combining palbociclib with retinoic acid affect neuroblastoma cells?",{"text":121,"@type":113},"Dual treatment with retinoic acid resets the oncogenic adrenergic regulatory circuit, further suppresses proliferation, and enhances differentiation while altering gene expression associated with improved patient survival.","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},447665,1791305668,{"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":52,"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,"preview_page_count":4},962090883892,"https://ap-avatar.wpscdn.com/avatar/e00115db34f3e0f11b?x-image-process=image/resize,m_fixed,w_180,h_180&k=1790152879550218658","Europe PMC unders uthManuscripts Europe M eC und Author Manuscripts  \nEurope PMC Funders Group  \nAuthor Manuscript  \nDev Cell. Author manuscript; available in PMC 2026 January 06.  \nPublished in final edited form as:  \nDev Cell. 2023 October 09; 58(19): 1967–1982.e8. doi:10.1016/j.devcel.2023.08.028 .  \nPalbociclib releases the latent differentiation capacity of neuroblastoma cells  \nKirsty M. Ferguson\\#1 , Sarah L. Gillen\\#1 , Lewis Chaytor1,2 , Evon Poon3 , Daniel Marcos 1,2 , Roshna Lawrence Gomez4 , Laura M. Woods 1,2 , Lidiya Mykhaylechko 1,2 , Louis Elfari5 , Barbara Martins da Costa3 , Yann Jamin6 , Jason S. Carroll7 , Louis Chesler3 , Fahad R. Ali4 , Anna Philpott 1,2,9,*  \n1Wellcome-MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, , Cambridge CB2 0AW, UK.  \n2 Department of Oncology, University of Cambridge, Cambridge CB2 0XZ, UK.  \n3 Division of Clinical Studies, The Institute of Cancer Research (ICR) and Royal Marsden NHS Trust, Sutton SM2 5NG, UK.  \n4College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai Healthcare City, P.O. Box 505055,, Dubai, United Arab Emirates.  \n5Wellcome-MRC Cambridge Stem Cell Institute Advanced Imaging Facility, Cambridge CB2 0AW, UK.  \n6 Division of Radiotherapy and Imaging, The Institute of Cancer Research (ICR) and Royal Marsden NHS Trust, Sutton SM2 5NG, UK.  \n7Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK.  \n\\# These authors contributed equally to this work.  \nSummary  \nNeuroblastoma is the most common extracranial solid tumor in infants, arising from developmentally stalled neural crest-derived cells. Driving tumor differentiation is a promising therapeutic approach for this devastating disease. Here, we show that the CDK4/6 inhibitor  \nThis work is licensed under a BY 4.0 International license.  \n*C9 Loeespd conontenct[ce: ap113@cam.ac.uk](ce: ap113@cam.ac.uk).  \nAuthor contributions  \nConceptualization, K.M.F., S.L.G., L. Chaytor, E.P., L. Chesler, and A.P.; functional experiments, K.M.F.; microscopy, K.M.F.; writing – original draft, reviewing & editing, K.M.F., S.L.G., and A.P.; writing – review & editing, E.P. and L. Chesler; NGS data processing, S.L.G. and L.M.W.; bioinformatic analysis, S.L.G.; western blotting, S.L.G.; preliminary investigation, L. Chaytor, E.P., D.M., L.M., and F.R.A.; RNA-seq and H3K27ac ChIP-seq experiments, L. Chaytor; in vivo work, E.P. and B.M.d.C.; PB + RA H3K27ac ChIP-seq experiments, R.L.G.; transmission electron microscopy sample processing and data acquisition, L.E.; MRI imaging, Y.J.; guidance on methodology, J.S.C; funding acquisition, L. Chesler, F.R.A., and A.P.; project administration, L. Chesler and A.P.; supervision, L. Chesler, F.R.A., and A.P.  \nDeclaration of interests  \nWe have filed an application seeking patent protection on the use of the combination CDK4/6 inhibitors and retinoic acid in neuroblastoma.  \nInclusion and diversity  \nWe support inclusive, diverse, and equitable conduct of research.  \nEurope PMC unders uthManuscripts Europe M eC und Author Manuscripts  \nFerguson et al. Page 2  \npalbociclib not only inhibits proliferation but induces extensive neuronal differentiation of adrenergic neuroblastoma cells. Palbociclib-mediated differentiation is manifested by extensive phenotypic and transcriptional changes accompanied by the establishment of an epigenetic program driving expression of mature neuronal features. In vivo palbociclib significantly inhibits tumor growth in mouse neuroblastoma models. Furthermore, dual treatment with retinoic acid resets the oncogenic adrenergic core regulatory circuit of neuroblastoma cells, further suppresses proliferation, and can enhance differentiation, altering gene expression in ways that significantly correlate with improved patient survival. We therefore identify palbociclib as a therapeutic approach to dramatically enhance neuro-blastoma differentiation efficacy tha","cbCaiimzQjOMBPLg","https://ap.wps.com/l/cbCaiimzQjOMBPLg","pdf",4133475,44,"English","# Summary\n# Abstract\n# Graphical abstract\n# Introduction\n## Normal development and differentiation context\n## Differentiation therapies and clinical motivation","[{\"question\":\"What problem does this work address in neuroblastoma?\",\"answer\":\"Neuroblastoma tumors fail to differentiate and remain in an immature state that drives tumor growth.\"},{\"question\":\"What role does palbociclib play in the study?\",\"answer\":\"Palbociclib inhibits proliferation and induces extensive neuronal differentiation, along with phenotypic, transcriptional, and epigenetic program changes.\"},{\"question\":\"How does combining palbociclib with retinoic acid affect neuroblastoma cells?\",\"answer\":\"Dual treatment with retinoic acid resets the oncogenic adrenergic regulatory circuit, further suppresses proliferation, and enhances differentiation while altering gene expression associated with improved patient survival.\"}]","Palbociclib releases the latent differentiation capacity of neuroblastoma cells | PDF",1790722116,111]