[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-378725-105":59,"doc-detail-378725-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","tumour-heterogeneity-and-the-consequent-practical-challenges-in-the-management-of-gastroenteropancreatic-neuroendocrine-neoplasms","Tumour Heterogeneity and the Consequent Practical Challenges in the Management of Gastroenteropancreatic Neuroendocrine Neoplasms","","Tumour heterogeneity is a frequent feature of neuroendocrine neoplasms and a major driver of treatment failure and disease progression. Genetic and epigenetic instability, cancer stem cell proliferation, and alterations in the tumour microenvironment create intra-tumoural differences in primary sites and metastases that may evolve during therapy under selective pressure. Gastroenteropancreatic disease relies on characteristics such as proliferation activity, somatostatin receptor expression, and grading; however, intra- and inter-tumour heterogeneity can produce inaccurate diagnostic, prognostic, and predictive results. This review synthesizes evidence on how heterogeneity affects management.",{"@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/tumour-heterogeneity-and-the-consequent-practical-challenges-in-the-management-of-gastroenteropancreatic-neuroendocrine-neoplasms/378725/",{"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/tumour-heterogeneity-and-the-consequent-practical-challenges-in-the-management-of-gastroenteropancreatic-neuroendocrine-neoplasms/378725.png","ImageObject",300,407,{"name":92,"@type":93},"Finn","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":29},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is tumour heterogeneity in gastroenteropancreatic neuroendocrine neoplasms?","Question",{"text":112,"@type":113},"Tumour heterogeneity refers to spatial and temporal variations occurring within a tumour (intra-tumour) or between tumour sites (inter-tumour), including genetic/epigenetic differences and variations in the tumour microenvironment.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Why does tumour heterogeneity affect diagnosis and treatment outcomes?",{"text":117,"@type":113},"Heterogeneity can evolve over time under selective pressure from treatment, leading to clonal expansion of subpopulations and potentially causing inaccurate assessment. This reduces the reliability of diagnostic, prognostic, and predictive tests.",{"name":119,"@type":110,"acceptedAnswer":120},"Which biomarkers are highlighted for gastroenteropancreatic NENs and how can heterogeneity influence them?",{"text":121,"@type":113},"Somatostatin receptor expression plays a major role in diagnosis and treatment, while Ki-67 is a valuable prognostic marker. However, intra- and inter-tumour heterogeneity may lead to inaccurate measurement and affect test reliability.","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},378725,1790461062,{"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":29,"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":26},34359740700684,"https://ap-avatar.wpscdn.com/avatar/1f400023980c374ae676?_k=1777273430885731487","cancers   \nReview  \nTumour Heterogeneity and the Consequent Practical Challenges in the Management of Gastroenteropancreatic  \nNeuroendocrine Neoplasms  \nIsabella Reccia 1, *, Madhava Pai 2, Jayant Kumar 2, Duncan Spalding 2 and Andrea Frilling 2, *  \nCitation: Reccia, I.; Pai, M.; Kumar, J.; Spalding, D.; Frilling, A. Tumour Heterogeneity and the Consequent Practical Challenges in the Management of Gastroenteropancreatic Neuroendocrine Neoplasms. Cancers 2023, 15, 1861. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/cancers15061861](10.3390/cancers15061861)  \nAcademic Editors: Vikas Prasad and Nat P. Lenzo  \nReceived: 14 February 2023  \nRevised: 10 March 2023  \nAccepted: 18 March 2023  \nPublished: 20 March 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 General Surgical and Oncology Unit, Policlinico San Pietro, Via Carlo Forlanini, 24036 Ponte San Pietro, Italy  \n2 Division of Surgery, Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0HS, UK  \n* Correspondence: [isabella.reccia@nhs.net](isabella.reccia@nhs.net) (I.R.); [a.frilling@imperial.ac.uk](a.frilling@imperial.ac.uk) (A.F.)  \nSimple Summary: Neuroendocrine tumours, recently reclassified as neuroendocrine neoplasms (NENs), are a heterogeneous group of tumours with variability in their disease course and outcome. Complex mechanisms involving spatial and temporal changes in tumour biology affect their treatment response and survival. Treatment strategies are often based on information regarding tumour stage and grade. Tumour heterogeneity, however, is a common phenomenon in NENs, and it is not uncommon for these neoplasms to show intra-and inter-tumour heterogeneity that may lead to incomplete understanding of their tumour biology and behaviour. This review summarises the available evidence on gastroenteropancreatic NEN heterogeneity and its impact on diagnosis and clinical management.  \nAbstract: Tumour heterogeneity is a common phenomenon in neuroendocrine neoplasms (NENs) and a significant cause of treatment failure and disease progression. Genetic and epigenetic instability, along with proliferation of cancer stem cells and alterations in the tumour microenvironment, manifest as intra-tumoural variability in tumour biology in primary tumours and metastases. This may changeover time, especially under selective pressure during treatment. The gastroenteropancreatic (GEP) tract is the most common site for NENs, and their diagnosis and treatment depends on the specific characteristics of the disease, in particular proliferation activity, expression of somatostatin receptors and grading. Somatostatin receptor expression has a major role in the diagnosis and treatment of GEP-NENs, while Ki-67 is also a valuable prognostic marker. Intra-and inter-tumour heterogeneity in GEP-NENS, however, may lead to inaccurate assessment of the disease and affect the reliability of the available diagnostic, prognostic and predictive tests. In this review, we summarise the current available evidence of the impact of tumour heterogeneity on tumour diagnosis and treatment of GEP-NENs. Understanding and accurately measuring tumour heterogeneity could better inform clinical decision making in NENs.  \nKeywords: neuroendocrine tumour; neuroendocrine neoplasms; gastroenteropancreatic; tumour heterogeneity; cell signalling pathway; biopsy; radioligand therapy; somatostatin analogues  \n1. Introduction  \nTumour heterogeneity refers to spatial and temporal variations that may occur within the tumour environment (intra-tumour) or within individual tumour foci, and also between tumour sites (inter-tumour) [1] . Such hete","cbCaiaE284rxGS9X","https://ap.wps.com/l/cbCaiaE284rxGS9X","pdf",1868732,24,"English","# Introduction\n## Tumour heterogeneity in NENs\n# Neuroendocrine neoplasms and classification\n## GEP-NENs terminology, differentiation, and grading","[{\"question\":\"What is tumour heterogeneity in gastroenteropancreatic neuroendocrine neoplasms?\",\"answer\":\"Tumour heterogeneity refers to spatial and temporal variations occurring within a tumour (intra-tumour) or between tumour sites (inter-tumour), including genetic/epigenetic differences and variations in the tumour microenvironment.\"},{\"question\":\"Why does tumour heterogeneity affect diagnosis and treatment outcomes?\",\"answer\":\"Heterogeneity can evolve over time under selective pressure from treatment, leading to clonal expansion of subpopulations and potentially causing inaccurate assessment. This reduces the reliability of diagnostic, prognostic, and predictive tests.\"},{\"question\":\"Which biomarkers are highlighted for gastroenteropancreatic NENs and how can heterogeneity influence them?\",\"answer\":\"Somatostatin receptor expression plays a major role in diagnosis and treatment, while Ki-67 is a valuable prognostic marker. However, intra- and inter-tumour heterogeneity may lead to inaccurate measurement and affect test reliability.\"}]","Tumour Heterogeneity and the Consequent Practical Challenges in the Management of Gastroenteropancreatic Neuroendocrine Neoplasms | PDF",1790232092]