[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-382738-105":59,"doc-detail-382738-en":129},{"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":122,"head_meta":124,"extra_data":126,"updated_unix":128},105,"en","the-dual-role-of-necroptosis-in-pancreatic-ductal-adenocarcinoma-review","The Dual Role of Necroptosis in Pancreatic Ductal Adenocarcinoma - Review","","Pancreatic cancer (PC) remains a leading cause of cancer death, with rising incidence and still poor survival, demanding new therapeutic strategies. Progress is limited by profound tumor heterogeneity and an incompletely understood interaction between cancer cells and the surrounding microenvironment. Necroptosis, a programmed cell death pathway, has attracted increasing attention. This review summarizes necroptosis’ historical background and analyzes the ongoing debate on its contribution to PC malignant progression.",{"@graph":69,"@context":121},[70,84,104],{"@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/the-dual-role-of-necroptosis-in-pancreatic-ductal-adenocarcinoma-review/382738/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":98,"encodingFormat":97,"isAccessibleForFree":99,"interactionStatistic":100},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/the-dual-role-of-necroptosis-in-pancreatic-ductal-adenocarcinoma-review/382738.png","ImageObject",300,407,{"name":92,"@type":93},"Melati","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-24",true,{"@type":101,"interactionType":102,"userInteractionCount":4},"InteractionCounter",{"@type":103},"ViewAction",{"@type":105,"mainEntity":106},"FAQPage",[107,113,117],{"name":108,"@type":109,"acceptedAnswer":110},"Why is pancreatic cancer still difficult to treat despite improved survival rates?","Question",{"text":111,"@type":112},"Pancreatic cancer shows low overall survival and remains poorly prognostic due to late diagnosis, aggressive biology, and chemoresistance, compounded by high tumor heterogeneity and an insufficiently understood tumor microenvironment interaction.","Answer",{"name":114,"@type":109,"acceptedAnswer":115},"What is necroptosis and why is it relevant to PDAC?",{"text":116,"@type":112},"Necroptosis is described as a caspase-independent mechanism of programmed cell death. 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The Dual Role of Necroptosis in Pancreatic Ductal Adenocarcinoma. Int. J. Mol. Sci. 2023, 24, 12633. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/ijms241612633](10.3390/ijms241612633)  \nAcademic Editor: Jörg D. Hoheisel  \nReceived: 9 July 2023  \nRevised: 5 August 2023  \nAccepted: 8 August 2023  \nPublished: 10 August 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 Department of Medicine and Aging Sciences, Section of Biomorphology,“G. d'Annunzio” University of Chieti-Pescara, 66100 Chieti, Italy  \n2 Laboratory of Cancer Pathology, Center for Advanced Studies and Technologies (CAST),“G. d'Annunzio”University of Chieti-Pescara, 66100 Chieti, Italy  \n3 Department of Medical, Oral and Biotechnological Sciences,“G. d'Annunzio” University of Chieti-Pescara, 66100 Chieti, Italy  \n4 Unit of Medical Genetics, Department of Biomedical Sciences, University of Messina, 98122 Messina, Italy  \n5 Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA  \n* Correspondence: [r.dipietro@unich.it](r.dipietro@unich.it)  \nAbstract: Pancreatic cancer (PC) is the seventh leading cause of cancer-related death. PC incidence has continued to increase by about 1% each year in both men and women. Although the 5-year relative survival rate of PC has increased from 3% to 12%, it is still the lowest among cancers. Hence, novel therapeutic strategies are urgently needed. Challenges in PC-targeted therapeutic strategies stem from the high PC heterogeneity and from the poorly understood interplay between cancer cells and the surrounding microenvironment. Signaling pathways that drive PC cell growth have been the subject of intense scrutiny and interest has been attracted by necroptosis, a distinct typeof programmed cell death. In this review, we provide a historical background on necroptosis and a detailed analysis of the ongoing debate on the role of necroptosis in PC malignant progression.  \nKeywords: pancreatic cancer; necroptosis; tumor microenvironment; cell death  \n1. Introduction  \nPancreatic Cancer (PC) currently is the seventh leading cause of cancer-related death [1] and is expected to become the second one by 2030 [2] .  \nPC incidence differs widely among countries: the highest age-standardized incidence is seen in Europe and North America, the lowest is recorded in Africa and South-Central Asia [3] .  \nLate diagnosis, together with chemoresistance and aggressive biology, have contributed to its poor prognosis and to the concept of PC as a “silent killer”.  \nEarly clinical manifestations are often vague, depending on the site of origin of the tumor. Approximately 70% of pancreatic tumors arise in the head of the pancreas and cause biliary obstruction leading to dark urine (49%) and jaundice (49%) . Patients with PC arising from the pancreas body or tail present other symptoms, such as abdominal pain, back pain, and cachexia-related symptoms (appetite loss, weight loss, fatigue) [4] .  \nPancreatic Ductal Adenocarcinoma (PDAC) is the most prevalent type of PC, representing more than 90% of cases [5] . It shows an overall 5-year survival rate of less than 5% and a median survival time of less than 6 months if untreated [6] .  \nStill today, there is a common and keen interest in filling the gaps","cbCaipZOaIqhhXmW","https://ap.wps.com/l/cbCaipZOaIqhhXmW","pdf",1693764,16,"English","# Abstract\n# 1. Introduction\n# 2. Pancreatic Ductal Adenocarcinoma (PDAC)","[{\"question\":\"Why is pancreatic cancer still difficult to treat despite improved survival rates?\",\"answer\":\"Pancreatic cancer shows low overall survival and remains poorly prognostic due to late diagnosis, aggressive biology, and chemoresistance, compounded by high tumor heterogeneity and an insufficiently understood tumor microenvironment interaction.\"},{\"question\":\"What is necroptosis and why is it relevant to PDAC?\",\"answer\":\"Necroptosis is described as a caspase-independent mechanism of programmed cell death. The review highlights a hypothesis that necroptosis may play an unexpected role in PDAC malignant progression through interactions between tumor cells and extra-epithelial compartments.\"},{\"question\":\"What does the review focus on regarding necroptosis in pancreatic cancer?\",\"answer\":\"It provides historical background on necroptosis and delivers a detailed analysis of the ongoing debate about whether and how necroptosis contributes to malignant progression, considering programmed cell death and the tumor microenvironment as a deciding factor.\"}]","The Dual Role of Necroptosis in Pancreatic Ductal Adenocarcinoma - Review | PDF"]