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Although once considered rare and slow-growing, GEP-NENs have shown rapidly rising global prevalence and incidence over recent decades. Evidence also indicates reduced life expectancy, suggesting more aggressive biology than previously assumed. This review consolidates advances and limitations in epidemiology, clinical presentation, pathology, molecular biology, diagnosis, and treatment to address delays in diagnosis and timely care.",{"@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/gastroenteropancreatic-neuroendocrine-neoplasms-current-development-challenges-and-clinical-perspectives/337808/",{"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/gastroenteropancreatic-neuroendocrine-neoplasms-current-development-challenges-and-clinical-perspectives/337808.png","ImageObject",300,407,{"name":92,"@type":93},"Hazel","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-27","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What are gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs)?","Question",{"text":112,"@type":113},"GEP-NENs are the most common subtype of neuroendocrine neoplasms arising from secretory cells of the neuroendocrine system within the gastroenteropancreatic area.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How have the prevalence and incidence of GEP-NENs changed over time?",{"text":117,"@type":113},"Worldwide prevalence and incidence have increased exponentially over the last three decades, with reported rises in both the United States and European populations.",{"name":119,"@type":110,"acceptedAnswer":120},"Why is timely diagnosis and treatment challenging for GEP-NENs?",{"text":121,"@type":113},"Clinicians, patients, and the public have limited understanding due to tumor rarity, and genetic variations complicate disease biology. 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Military Medical Research (2024) 11:35  \n[https://doi.org/10.1186/s40779-024-00535-6](https://doi.org/10.1186/s40779-024-00535-6)  \nREVIEW Open Access  \nGastroenteropancreatic neuroendocrine  \nneoplasms: current development, challenges, and clinical perspectives  \nXian‑Bin Zhang1†, Yi‑Bao Fan 1,2†, Rui Jing3†, Mikiyas Amare Getu1†, Wan‑Ying Chen1,2, Wei Zhang1, Hong‑Xia Dong4, Tikam Chand Dakal5, Akhtar Hayat6, Hua‑Jun Cai 1, Milad Ashrafizadeh1, A. M. Abd El‑Aty7,8, Ahmet Hacimuftuoglu8, Peng Liu1, Tian‑Feng Li9, Gautam Sethi10, Kwang Seok Ahn11, Yavuz Nuri Ertas 12,13,14, Min‑Jiang Chen15, Jian‑Song Ji15, Li Ma16 and Peng Gong1*  \nAbstract  \nNeuroendocrine neoplasms (NENs) are highly heterogeneous and potentially malignant tumors arising from secre‑ tory cells of the neuroendocrine system. Gastroenteropancreatic neuroendocrine neoplasms (GEP‑NENs) are the most common subtype of NENs. Historically, GEP‑NENs have been regarded as infrequent and slow‑growing malignancies; however, recent data have demonstrated that the worldwide prevalence and incidence of GEP‑NENs have increased exponentially over the last three decades. In addition, an increasing number of studies have proven that GEP‑NENs result in a limited life expectancy. These findings suggested that the natural biology of GEP‑NENs is more aggres‑ sive than commonly assumed. Therefore, there is an urgent need for advanced researches focusing on the diagnosis and management of patients with GEP‑NENs. In this review, we have summarized the limitations and recent advance‑ ments in our comprehension of the epidemiology, clinical presentations, pathology, molecular biology, diagnosis, and treatment of GEP‑NETs to identify factors contributing to delays in diagnosis and timely treatment of these patients.  \nKeywords Gastroenteropancreatic neuroendocrine neoplasms (GEP‑NENs), Neuroendocrine neoplasms (NENs), Diagnosis, Chemotherapy, Immunotherapy  \nBackground  \nNeuroendocrine neoplasms (NENs) originate from specialized secretory cells within the diffuse neuroendocrine system, with approximately two-thirds manifesting in the gastroenteropancreatic system [1–3]. Although they are uncommon, gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) have significantly increased in  \n†Xian‑Bin Zhang, Yi‑Bao Fan, Rui Jing and Mikiyas Amare Getu contributed equally to this work.  \n*Correspondence:  \nPeng Gong  \n[doctorgongpeng@szu.edu.cn](doctorgongpeng@szu.edu.cn)  \nFull list of author information is available at the end of the article  \nglobal prevalence and incidence over the past three decades. This class of tumors exhibits a wide range of diversity and complexity, varying from indolent to aggressive. Furthermore, due to their rarity, there is a lack of understanding regarding diagnosis and treatment among clinicians, patients, and the general public. Genetic variations further complicate our understanding of disease biology and hinder the development of targeted therapies [4, 5]. Consequently, effective strategies for diagnosing and treating these tumors are lacking. Moreover, the prognosis of GEP-NENs is uncertain due to the absence of reliable prognostic markers, often leading to delayed diagnoses at advanced stages [4–7]. Therefore, it is crucial to conduct advanced research and develop  \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","cbCaieoNWECgzEn1","https://ap.wps.com/l/cbCaieoNWECgzEn1","pdf",2874069,"English","# Abstract\n# Background\n# Epidemiology\n## Incidence trends worldwide\n## Regional comparisons and contributing factors","[{\"question\":\"What are gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs)?\",\"answer\":\"GEP-NENs are the most common subtype of neuroendocrine neoplasms arising from secretory cells of the neuroendocrine system within the gastroenteropancreatic area.\"},{\"question\":\"How have the prevalence and incidence of GEP-NENs changed over time?\",\"answer\":\"Worldwide prevalence and incidence have increased exponentially over the last three decades, with reported rises in both the United States and European populations.\"},{\"question\":\"Why is timely diagnosis and treatment challenging for GEP-NENs?\",\"answer\":\"Clinicians, patients, and the public have limited understanding due to tumor rarity, and genetic variations complicate disease biology. The lack of reliable prognostic markers often results in delayed diagnosis at advanced stages.\"}]","Gastroenteropancreatic neuroendocrine neoplasms - current development, challenges, and clinical perspectives | PDF",1790020734]