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Therapeutic options—including surgery, radiotherapy, immunological and targeted strategies—provide only limited survival gains. This review focuses on Mucin 1 (MUC1), a transmembrane glycoprotein that is aberrantly glycosylated and frequently overexpressed in pancreatic cancer, promoting invasive behavior, metastasis, and drug resistance. 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Szewczuk  \nReceived: 11 December 2024  \nRevised: 3 February 2025  \nAccepted: 11 February 2025  \nPublished: 13 February 2025  \nCitation: Dieli, R.; Lioy, R.; Crispo, F.; Cascelli, N.; Martinelli, M.; Lerose, R.; Telesca, D.; Milella, M.R.; Colella, M.; Loperte, S.; et al. The Oncoprotein Mucin 1 in Pancreatic Cancer Onset and Progression: Potential Clinical Implications. Biomolecules 2025, 15, 275 . [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)biom15020275  \nCopyright: © 2025 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://creativecommons.org/](https://creativecommons.org/)[ ](https://creativecommons.org/)[licenses/by/4.0/](licenses/by/4.0/)) .  \n1 Laboratory of Pre-Clinical and Translational Research, Centro di Riferimento Oncologico della  \nBasilicata (IRCCS-CROB), 85028 Rionero in Vulture, Italy; [rosalia.dieli@crob.it](rosalia.dieli@crob.it) (R.D.); [rosa.lioy@crob.it](rosa.lioy@crob.it) (R.L.);  \n[nicoletta.cascelli@crob.it](nicoletta.cascelli@crob.it) (N.C.); [mara.martinelli@crob.it](mara.martinelli@crob.it) (M.M.); [carmela.mazzoccoli@crob.it](carmela.mazzoccoli@crob.it) (C.M.)  \n2 Hospital Pharmacy, Centro di Riferimento Oncologico della Basilicata (IRCCS-CROB), 85028 Rionero in  \nVulture, Italy; [rosa.lerose@crob.it](rosa.lerose@crob.it) (R.L.); [donatella.telesca@crob.it](donatella.telesca@crob.it) (D.T.); mariarita.milella@crob.it (M.R.M.)  \n3 Department of Systems Medicine, University of Rome “Tor Vergata”, 00133 Rome, Italy; [marco.colella@uniroma2.it](marco.colella@uniroma2.it)  \n4 Institute of Methodologies for Environmental Analysis, National Research Council, 85050 Tito Scalo, Italy; [simona.loperte@cnr.it](simona.loperte@cnr.it)  \n* Correspondence: [fabiana.crispo@crob.it](fabiana.crispo@crob.it)  \n† These authors contributed equally to this work.  \nAbstract: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy characterized by poor prognosis, therapeutic resistance, and frequent recurrence. Current therapeutic options for PDAC include surgery, radiotherapy, immunological and targeted approaches. However, all these therapies provide only a slight improvement in patient survival. Consequently, the discovery of novel specific targets is becoming a priority to develop more effective treatments for PDAC. Mucin 1 (MUC1), a transmembrane glycoprotein, is aberrantly glycosylated and frequently overexpressed in pancreatic cancer. Recent studies highlighted the role of this oncoprotein in pancreatic carcinogenesis and its involvement in the acquisition of typical aggressive features of PDAC, like local invasion, metastases, and drug resistance. This review explores the mechanisms by which MUC1 contributes to cancer onset and progression, with a focus on its potential role as a biomarker and novel therapeutic target for pancreatic adenocarcinoma treatment.  \nKeywords: pancreatic ductal adenocarcinoma; MUC1; tumor microenvironment; EMT; anoikis; target therapy  \n1. Introduction  \nPancreatic cancer is one of the most aggressive and lethal types of neoplastic disorders. Globally it represents the sixth-leading cause of cancer-related deaths [1], with the lowest 5-year relative survival from diagnosis among all solid tumors [2–4] . The etiology of pancreatic ductal adenocarcinoma (PDAC) is complex and multifactorial, with cigarette smoking and family history being primary risk factors. Other contributing factors include chronic pancreatitis, age, male gender, type 1 diabetes, obesi","cbCaihKp9CGPk3pT","https://ap.wps.com/l/cbCaihKp9CGPk3pT","pdf",1688375,21,"English","# Abstract\n# Keywords\n# 1. Introduction\n## Pancreatic cancer burden and risk factors\n## PDAC development and precursor lesions\n## Tumor progression features and recurrence","[{\"question\":\"Why is pancreatic ductal adenocarcinoma (PDAC) difficult to treat?\",\"answer\":\"PDAC is associated with poor prognosis, frequent recurrence, and therapeutic resistance, while current therapies yield only slight survival improvement.\"},{\"question\":\"What is MUC1 and how is it involved in PDAC?\",\"answer\":\"MUC1 is a transmembrane glycoprotein that is aberrantly glycosylated and frequently overexpressed in pancreatic cancer. Studies link it to aggressive traits such as local invasion, metastases, and drug resistance.\"},{\"question\":\"How does the review evaluate MUC1 for clinical use?\",\"answer\":\"It explores the mechanisms by which MUC1 contributes to cancer onset and progression, emphasizing its potential role as a biomarker and as a novel therapeutic target.\"}]","The Oncoprotein Mucin 1 in Pancreatic Cancer Onset and Progression - Potential Clinical Implications | PDF",1790216395,53]