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An alarming trend of rising GI malignancy diagnoses, especially in younger age groups, underscores the need for discoveries in liquid-based biomarkers that facilitate both early detection and optimal disease management. Extracellular vesicles (EVs) not only constitute promising nano-sized biomarkers, but also, via bioengineering, have shown a great therapeutic potential, with artificial intelligence (AI) revolutionizing their research via the selection of the best biomarkers from omics, the recognition of pathophysiological patterns, and facilitating a faster drug-development via AI-driven EV engineering, drug delivery modeling, and target identification. In this review, we will provide a clear insight into the implementation of AI methodologies in EV-based biomarker discovery and therapeutics for pancreatic and hepatobiliary cancer.<\/jats:p>","DOI":"10.3390\/ijms27031524","type":"journal-article","created":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T10:02:57Z","timestamp":1770199377000},"page":"1524","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Exploring the Role of Extracellular Vesicles in Pancreatic and Hepatobiliary Cancers: Advances Through Artificial Intelligence"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0080-9032","authenticated-orcid":false,"given":"Eleni Myrto","family":"Trifylli","sequence":"first","affiliation":[{"name":"Gastrointestinal-Liver Unit, 2nd Department of Internal Medicine, General Hospital of Athens \u201cHippocratio\u201d, National and Kapodistrian University of Athens, 114 Vas Sofias, 11527 Athens, Greece"},{"name":"Institute of Molecular Medicine and Biomedical Research (IMBE), 11527 Athens, Greece"},{"name":"Laboratory of Reliability and Quality Control in Laboratory Hematology (HemQcR), Department of Biomedical Sciences, Section of Medical Laboratories, School of Health & Caring Sciences, University of West Attica (UniWA), Ag. Spyridonos Str., 12243 Egaleo, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1226-9560","authenticated-orcid":false,"given":"Athanasios","family":"Angelakis","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Data Science, Amsterdam University Medical Center, 1105 Amsterdam, AZ, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sotirios P.","family":"Fortis","sequence":"additional","affiliation":[{"name":"Laboratory of Reliability and Quality Control in Laboratory Hematology (HemQcR), Department of Biomedical Sciences, Section of Medical Laboratories, School of Health & Caring Sciences, University of West Attica (UniWA), Ag. 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