{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:24:33Z","timestamp":1792628673975,"version":"4.5.0"},"reference-count":96,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T00:00:00Z","timestamp":1758153600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pancreatic cancer remains a lethal disease despite advances in surgery and systemic treatment in the last two decades, underscoring the urgent need to better understand its biological underpinnings. Despite remarkable advances in the molecular characterization of pancreatic ductal adenocarcinoma (PDAC), clinically actionable biomarkers remain scarce, and current treatment remains empiric. Transcriptomic subtypes such as \u201cclassical\u201d and \u201cbasal-like\u201d offer some prognostic value, but their ability to guide real-time treatment decisions is limited. In this review, we explore the limitations of current biomarker strategies, in particular subtype-based classifications, and argue for a functional reframing of biomarker development in PDAC, centered on patient-derived organoids (PDOs). We explore four key domains in which PDOs deepen our understanding of therapeutic response and resistance, namely, drug response phenotyping, modeling chemoresistance, incorporating tumor microenvironmental complexity through co-culture systems, and more functional profiling through proteomic and metabolomic approaches. Together, these applications move PDOs beyond static avatars of the tumor to dynamic platforms capable of capturing clinically relevant biology. As functional precision medicine gains traction, PDOs may offer a path to more tailored, responsive treatment strategies in a cancer where new options are urgently needed.<\/jats:p>","DOI":"10.3390\/ijms26189083","type":"journal-article","created":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T12:54:26Z","timestamp":1758200066000},"page":"9083","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Functional Precision in Pancreatic Cancer: Redefining Biomarkers with Patient-Derived Organoids"],"prefix":"10.3390","volume":"26","author":[{"given":"Claire Alexandra","family":"Chew","sequence":"first","affiliation":[{"name":"Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore"},{"name":"Institute of Health Innovation & Technology, National University of Singapore, Singapore 117599, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6740-3881","authenticated-orcid":false,"given":"Cheng Mun","family":"Wun","sequence":"additional","affiliation":[{"name":"Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore"},{"name":"Institute of Health Innovation & Technology, National University of Singapore, Singapore 117599, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3210-2024","authenticated-orcid":false,"given":"Yi Fang","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore"},{"name":"Institute of Health Innovation & Technology, National University of Singapore, Singapore 117599, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng Ean","family":"Chee","sequence":"additional","affiliation":[{"name":"Department of Haematology-Oncology, National University Cancer Institute Singapore, Singapore 119074, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khek Yu","family":"Ho","sequence":"additional","affiliation":[{"name":"Department of Medicine, National University of Singapore, Singapore 119077, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glenn Kunnath","family":"Bonney","sequence":"additional","affiliation":[{"name":"Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore"},{"name":"Institute of Health Innovation & Technology, National University of Singapore, Singapore 117599, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,18]]},"reference":[{"key":"ref_1","first-page":"7","article-title":"Cancer statistics, 2018","volume":"68","author":"Siegel","year":"2018","journal-title":"CA Cancer J. 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