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Cells within the tumor microenvironment (TME) shape tumor metabolism, restrict drug delivery, strengthen immune-suppression programs, and promote resistance to both chemotherapy and immunotherapy. Intercellular molecular crosstalk involves key TME populations such as cancer-associated fibroblasts, myeloid-derived suppressor cells, pancreatic stellate cells, tumor-associated macrophages, tumor-associated neutrophils, and regulatory T cells.",{"@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":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/precision-targeting-strategies-in-pancreatic-cancer-the-role-of-tumor-microenvironment/332384/",{"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/precision-targeting-strategies-in-pancreatic-cancer-the-role-of-tumor-microenvironment/332384.png","ImageObject",300,407,{"name":92,"@type":93},"Ezra","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-31","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",11,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"Why is pancreatic ductal adenocarcinoma (PDAC) difficult to treat?","Question",{"text":113,"@type":114},"PDAC faces clinical hurdles such as late-stage diagnosis and the development of therapeutic resistance. 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Gargalionis 2,†, Kostas A. Papavassiliou 3, Christos Adamopoulos 1,4, * and Athanasios G. Papavassiliou 1, *  \nCitation: Vitorakis, N.; Gargalionis,  \nA.N.; Papavassiliou, K.A.;  \nAdamopoulos, C.; Papavassiliou, A.G. Precision Targeting Strategies in Pancreatic Cancer: The Role of Tumor Microenvironment. Cancers 2024, 16, 2876. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)cancers16162876  \nAcademic Editor: Huey-Jen Lin  \nReceived: 21 July 2024  \nRevised: 14 August 2024  \nAccepted: 17 August 2024  \nPublished: 19 August 2024  \nCopyright: © 2024 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 Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece; [nikolas.vitorakis@gmail.com](nikolas.vitorakis@gmail.com)  \n2 Department of Clinical Biochemistry,‘Attikon’ University General Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece; [agargal@med.uoa.gr](agargal@med.uoa.gr)  \n3 First University Department of Respiratory Medicine,‘Sotiria’ Hospital, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece; [konpapav@med.uoa.gr](konpapav@med.uoa.gr)  \n4 Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA  \n* Correspondence: [cadamop@med.uoa.gr](cadamop@med.uoa.gr) (C.A.); [papavas@med.uoa.gr](papavas@med.uoa.gr) (A.G.P.); Tel.: +30-210-746-2709 (C.A.)† These authors contributed equally to this work.  \nSimple Summary: Pancreatic cancer is one of the most lethal forms of malignancies; therefore, new treatment strategies are required to increase the patients’ survival. It has been established that different cell types that surround pancreatic cancer cells, thus forming the tumor microenvironment, are responsible for tumorigenicity and inefficacy of treatments, including immunotherapy. In the present review, we aim to summarize current knowledge regarding the molecular mechanisms underpinning the interaction of cancer cells with cells of their microenvironment and discuss associated strategies to improve treatment results.  \nAbstract: Pancreatic cancer demonstrates an ever-increasing incidence over the last years and represents one of the top causes of cancer-associated mortality. Cells of the tumor microenvironment (TME) interact with cancer cells in pancreatic ductal adenocarcinoma (PDAC) tumors to preserve cancer cells’metabolism, inhibit drug delivery, enhance immune suppression mechanisms and finally develop resistance to chemotherapy and immunotherapy. New strategies target TME genetic alterations and specific pathways in cell populations of the TME. Complex molecular interactions develop between PDAC cells and TME cell populations including cancer-associated fibroblasts, myeloid-derived suppressor cells, pancreatic stellate cells, tumor-associated macrophages, tumor-associated neutrophils, and regulatory T cells. In the present review, we aim to fully explore the molecular landscape of the pancreatic cancer TME cell populations and discuss current TME targeting strategies to provide thoughts for further research and preclinical testing.  \nKeywords: pancreatic ductal adenocarcinoma (PDAC); pancreatic cancer; tumor microenvironment (TME); cancer-associated fibroblasts (CAFs); myeloid-derived suppressor cells (MDSCs); tumorassociated macrophages (TAMs); immunotherapy  \n1. Introduction  \nPancreatic cancer ranks among the top causes of cancer-related deaths globally, with its incidence havin","cbCairOwsSWgq1fR","https://ap.wps.com/l/cbCairOwsSWgq1fR","pdf",1548003,26,"English","# Introduction\n## Tumor microenvironment and treatment resistance\n## Molecular interactions in PDAC\n# Targeting strategies","[{\"question\":\"Why is pancreatic ductal adenocarcinoma (PDAC) difficult to treat?\",\"answer\":\"PDAC faces clinical hurdles such as late-stage diagnosis and the development of therapeutic resistance. Delayed diagnosis is often linked to minimal symptoms early in disease.\"},{\"question\":\"How does the tumor microenvironment (TME) affect therapy outcomes?\",\"answer\":\"TME cells interact with cancer cells to preserve tumor metabolism, inhibit drug delivery, enhance immune-suppression mechanisms, and ultimately develop resistance to chemotherapy and immunotherapy.\"},{\"question\":\"Which TME cell populations are highlighted as important in the review?\",\"answer\":\"The review discusses molecular interactions involving cancer-associated fibroblasts, myeloid-derived suppressor cells, pancreatic stellate cells, tumor-associated macrophages, tumor-associated neutrophils, and regulatory T cells.\"}]","Precision Targeting Strategies in Pancreatic Cancer - The Role of Tumor Microenvironment | PDF",1789997952,66]