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Contemporary chemotherapy can rapidly induce resistance, increasing the need for more effective treatments. The ubiquitin-proteasome system (UPS) is central to eukaryotic protein degradation and apoptosis control. UPS inhibition can drive apoptotic death in pancreatic cancer cells, and proteasome inhibitors such as bortezomib highlight therapeutic susceptibility through mechanisms linked to ER stress and apoptosis.",{"@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/regulation-of-ubiquitin-proteasome-system-and-its-relative-pathways-in-pancreatic-adenocarcinoma/337323/",{"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/regulation-of-ubiquitin-proteasome-system-and-its-relative-pathways-in-pancreatic-adenocarcinoma/337323.png","ImageObject",300,407,{"name":92,"@type":93},"Ophelia","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":39},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why is the ubiquitin-proteasome system (UPS) important in pancreatic adenocarcinoma?","Question",{"text":112,"@type":113},"UPS is an essential, highly conserved mechanism for degrading proteins in eukaryotes. It helps remove misfolded or damaged proteins through ubiquitination, and disturbances in UPS activity can influence apoptosis and tumor behavior.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How can inhibiting UPS affect pancreatic cancer cells?",{"text":117,"@type":113},"Inhibition of the UPS can trigger apoptotic death of pancreatic cancer cells. Proteasome inhibitors such as bortezomib are associated with increased ER stress and apoptosis in these cells.",{"name":119,"@type":110,"acceptedAnswer":120},"Why are UPS-targeted therapies not as successful clinically despite promising preclinical results?",{"text":121,"@type":113},"Although UPS-based therapies show favorable effects in vitro and in vivo, clinical outcomes have not matched expectations, indicating gaps between experimental results and real-world patient responses.","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},337323,1790109752,{"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":39,"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},7971461741311,"https://ap-avatar.wpscdn.com/avatar/74000253aff267980c6?x-image-process=image/resize,m_fixed,w_180,h_180&k=1779345379180704826","Regulation of ubiquitin-proteasome system and its relative pathways in pancreatic adenocarcinoma  \nBahareh Shateri Amiri1 ID , Mehrasa Naserranjbar2, AyAna Mirhaji3, Alireza Hejrati2, Lina Hejrati2, Fatemeh Aliabadi4* ID 1Department of Internal Medicine, School of Medicine, Hazrat-e Rasool General Hospital, University of Medical Sciences, Tehran, Iran  \n2School of Medicine, Iran University of Medical Sciences, Tehran, Iran 3Tabatabaei Highschool, Shiraz, Iran  \n4Physiology Research Center, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran  \nArticle Info  \nArticle Type:  \nReview  \nArticle History:  \nReceived: 12 Jul. 2023  \nRevised: 18 Apr. 2024  \nAccepted: 30 Apr. 2024  \nePublished: 27 Oct. 2024  \nKeywords:  \nPancreatic cancer  \nPancreatic adenocarcinoma Ubiquitin-proteasome system Regulating factors  \nAbstract  \nIntroduction: Pancreatic cancer, which results from the uncontrolled growth of pancreatic cells, is the fourth most frequent cause of cancerrelated mortality in the United States. About 90% of instances of pancreatic cancer are pancreatic adenocarcinomas, and occasionally \"pancreatic cancer\" is used exclusively to describe this subtype. Nab-paclitaxel, gemcitabine, and FOLFIRINOX are examples of modern chemotherapeutic drugs that have the ability to quickly confer resistance in pancreatic tumor cells. Therefore, in order to treat this dreadful condition, it is essential to develop more effective medicines. Inhibition of the ubiquitin-proteasome system (UPS) causes pancreatic cancer cells to die apoptotically. In eukaryotes, UPS is an essential mechanism for protein breakdown. Pancreatic cancer cells are more susceptible to endoplasmic reticulum stress (endoplasmic reticulum [ER] stress) and apoptosis when treated with bortezomib, a proteasome inhibitor that is the first in this group of drugs approved for the treatment of cancer, especially multiple myeloma.  \nMethods: Searching through PubMed and Google Scholar and gathering data.  \nResults: UPS is still a popular target for pancreatic cancer treatment among researchers. However, despite the favorable results of UPS-based therapies in vitro and in vivo, the clinical results are not as promising as expected.  \nConclusion: A deep understanding of it, is essential to achieving the maximum results. In this review, we aim to look into the UPS along with searching for the novelist therapies for pancreatic adenocarcinoma based on manipulating it.  \nIntroduction  \nThe most common cancer among those with a bad prognosis in western populations is pancreatic cancer. In terms of new instances, this cancer is currently in tenth place.1 Globally, the incidence of all forms of pancreatic cancer (85% of whom are adenocarcinomas) varies from one to ten cases per 100 000 persons.2 In the Western world, pancreatic cancer ranks fourth for men and fifth for women in terms of cancer-related death.3 Europe and North America have the highest age-standardized incidence, while Africa and South Central Asia have the lowest.4 It is uncommon for anyone under the age of 40  \nto be diagnosed with pancreatic adenocarcinoma.2 The incidence is highest in the seventh and eighth decades of life.5  \nAmong all pancreatic malignancies, pancreatic adenocarcinoma is the most common, accounting for 80% of them.5,6 Over the next 10 years, lung cancer is expected to be passed on by pancreatic ductal adenocarcinoma (PDAC), the most common form of pancreatic cancer, as the second-leading cause of cancer-related mortality in the US.7,8 About 10–20% of pancreatic carcinomas are resectable and potentially curable, and the five-year survival rate is only 4%; hence, the majority of pancreatic  \n*Corresponding author: Fatemeh Aliabadi, Email: [aliabadi96f@gmail.com](aliabadi96f@gmail.com)  \n © 2025 The Author(s) . This work is published by BioImpacts as an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ([http://creativecommons.org/license","cbCaiqXQDnhNmTpS","https://ap.wps.com/l/cbCaiqXQDnhNmTpS","pdf",1427031,22,"English","# Introduction\n# Protein Homeostasis (Proteostasis) and UPS Role\n# Pancreatic Adenocarcinoma Epidemiology and Prognosis","[{\"question\":\"Why is the ubiquitin-proteasome system (UPS) important in pancreatic adenocarcinoma?\",\"answer\":\"UPS is an essential, highly conserved mechanism for degrading proteins in eukaryotes. It helps remove misfolded or damaged proteins through ubiquitination, and disturbances in UPS activity can influence apoptosis and tumor behavior.\"},{\"question\":\"How can inhibiting UPS affect pancreatic cancer cells?\",\"answer\":\"Inhibition of the UPS can trigger apoptotic death of pancreatic cancer cells. Proteasome inhibitors such as bortezomib are associated with increased ER stress and apoptosis in these cells.\"},{\"question\":\"Why are UPS-targeted therapies not as successful clinically despite promising preclinical results?\",\"answer\":\"Although UPS-based therapies show favorable effects in vitro and in vivo, clinical outcomes have not matched expectations, indicating gaps between experimental results and real-world patient responses.\"}]","Regulation of Ubiquitin-Proteasome System and Its Relative Pathways in Pancreatic Adenocarcinoma | PDF",1790018591,55]