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Functional and non-functional subtypes, slow growth, and reliance on retrospective therapeutic data make development difficult. This review synthesizes established cell lines, 3D cultures, and whole-organism models such as mice and zebrafish, comparing strengths and limitations of each approach. Future technological advances are expected to expand model quality and research impact.",{"@graph":69,"@context":123},[70,84,106],{"@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/models-in-pancreatic-neuroendocrine-neoplasms-current-perspectives-and-future-directions/379124/",{"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/models-in-pancreatic-neuroendocrine-neoplasms-current-perspectives-and-future-directions/379124.png","ImageObject",300,407,{"name":92,"@type":93},"Quinn Holloway","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-03","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",12,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"Why are pancreatic neuroendocrine neoplasms (pNENs) difficult to study and develop therapies for?","Question",{"text":113,"@type":114},"Their rarity, slow growth, and lack of early disease indicators make research and therapeutic development challenging, and clinical therapeutics often rely on retrospective analyses.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"What types of study models are covered in the review?",{"text":118,"@type":114},"The review covers established cell lines, 3D cell models, and whole-organism models including mice and zebrafish.",{"name":120,"@type":111,"acceptedAnswer":121},"How do model choice factors affect research in pNENs?",{"text":122,"@type":114},"Choosing a model requires considering factors such as complexity, accuracy, and cost to best match the research question and to validate data for cancer research needs.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},379124,1790506976,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":146},2336474466712,"https://ap-avatar.wpscdn.com/davatar_a8503ba1806abce46bf441b54a3ca4cd","cancers   \nReview  \nModels in Pancreatic Neuroendocrine Neoplasms: Current Perspectives and Future Directions  \nSteven D. Forsythe 1, Tracey Pu 2, Stephen G. Andrews 1, James P. Madigan 1 and Samira M. Sadowski 1, *  \nCitation: Forsythe, S.D.; Pu, T.; Andrews, S.G.; Madigan, J.P.; Sadowski, S.M. Models in Pancreatic Neuroendocrine Neoplasms: Current Perspectives and Future Directions. Cancers 2023, 15, 3756. [https://](https://)[ ](https://)[doi.org/10.3390/cancers15153756](doi.org/10.3390/cancers15153756)  \nAcademic Editor: Kay-Uwe Wagner  \nReceived: 19 June 2023  \nRevised: 21 July 2023  \nAccepted: 23 July 2023  \nPublished: 25 July 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 Neuroendocrine Cancer Therapy Section, Surgical Oncology Program, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA; [steven.forsythe@nih.gov](steven.forsythe@nih.gov) (S.D.F.); [stephen.andrews2@nih.gov](stephen.andrews2@nih.gov) (S.G.A.); [james.madigan@nih.gov](james.madigan@nih.gov) (J.P.M.)  \n2 Surgical Oncology Program, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA; [tracey.pu@nih.gov](tracey.pu@nih.gov)  \n* Correspondence: [samira.sadowski@nih.gov](samira.sadowski@nih.gov)  \nSimple Summary: Pancreatic neuroendocrine neoplasms (pNENs) are a rare and understudied cancer. Some of this low knowledge base is due to a historical lack of study models. Study models have tremendous implications for validating data for a range of cancer research topics, including treatment development. Therefore, correctly choosing a model is imperative and needs to consider a range of factors pertinent to the research question. In this review, we summarized the current field of models in pNENs. We considered factors, including complexity, accuracy, and cost, in models ranging from cell line cultures, 3D cultures, and whole organismal models, including mice and zebrafish. Improving the number and quality of models available will lead to new breakthroughs in treating pNENs and may lead to findings beneficial for other cancers.  \nAbstract: Pancreatic neuroendocrine neoplasms (pNENs) are a heterogeneous group of tumors derived from multiple neuroendocrine origin cell subtypes. Incidence rates for pNENs have steadily risen over the last decade, and outcomes continue to vary widely due to inability to properly screen. These tumors encompass a wide range of functional and non-functional subtypes, with their rarity and slow growth making therapeutic development difficult as most clinically used therapeutics are derived from retrospective analyses. Improved molecular understanding of these cancers has increased our knowledge of the tumor biology for pNENs. Despite these advances in our understanding of pNENs, there remains a dearth of models for further investigation. In this review, we will cover the current field of pNEN models, which include established cell lines, animal models such as mice and zebrafish, and three-dimensional (3D) cell models, and compare their uses in modeling various disease aspects. While no study model is a complete representation of pNEN biology, each has advantages which allow for new scientific understanding of these rare tumors. Future efforts and advancements in technology will continue to create new options in modeling these cancers.  \nKeywords: pancreatic neuroendocrine neoplasms; models; cell lines; mouse models; 3D cell culture  \n1. Introduction  \nPancreatic neuroendocrine neoplasms (pNENs) are a rare class of tumors which derive from neuroendocrine cells located in the islets of the pancreas. They are the third most common neuroendocrine tumor subtype in the gastro–ente","cbCailndCBhgbr67","https://ap.wps.com/l/cbCailndCBhgbr67","pdf",2125687,35,"English","# Simple Summary\n# Abstract\n# Keywords\n# 1. Introduction","[{\"question\":\"Why are pancreatic neuroendocrine neoplasms (pNENs) difficult to study and develop therapies for?\",\"answer\":\"Their rarity, slow growth, and lack of early disease indicators make research and therapeutic development challenging, and clinical therapeutics often rely on retrospective analyses.\"},{\"question\":\"What types of study models are covered in the review?\",\"answer\":\"The review covers established cell lines, 3D cell models, and whole-organism models including mice and zebrafish.\"},{\"question\":\"How do model choice factors affect research in pNENs?\",\"answer\":\"Choosing a model requires considering factors such as complexity, accuracy, and cost to best match the research question and to validate data for cancer research needs.\"}]","Models in Pancreatic Neuroendocrine Neoplasms - Current Perspectives and Future Directions | PDF",1790234219,88]