{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T14:24:50Z","timestamp":1788531890777,"version":"build-2803163510"},"reference-count":267,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest malignancies worldwide because of delayed diagnosis, rapid metastatic progression, profound immune suppression, and limited therapeutic responsiveness. The pancreatic tumor microenvironment is characterized by severe hypoxia, stromal desmoplasia, metabolic stress, and oxidative imbalance, all of which contribute to tumor progression and resistance to therapy. Among immune cells involved in antitumor defense, natural killer (NK) cells play an important role through direct cytotoxicity and cytokine production. However, NK-cell activity is frequently impaired in PDAC due to oxidative stress, altered nutrient availability, mitochondrial dysfunction, and dysregulated signaling pathways such as AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR). This review examines current evidence regarding the interactions among redox biology, nutrient sensing, NK-cell metabolism, and pancreatic cancer progression. Importantly, much of the available evidence derives from in vitro studies, animal models, or early-phase clinical investigations, and several findings remain controversial or inconsistent. Further well-designed clinical trials are needed to determine whether nutritional interventions, vitamin supplementation, and strategies targeting metabolic and redox pathways can safely and effectively enhance NK-cell function and improve clinical outcomes in patients with PDAC.<\/jats:p>","DOI":"10.3390\/ijms27177893","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T13:50:44Z","timestamp":1788529844000},"page":"7893","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting Reactive Species Stress and Nutrient Sensing to Enhance NK-Cell Function: Mechanistic Strategies for Overcoming Pancreatic Cancer Progression and Resistance Through Supplement Therapy"],"prefix":"10.3390","volume":"27","author":[{"given":"Sara","family":"Fanijavadi","sequence":"first","affiliation":[{"name":"SF-Medic Oncology Hub, 28924 Madrid, Spain"},{"name":"Cancer Polyclinic, Levanger Hospital, 7601 Levanger, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0020-1537","authenticated-orcid":false,"given":"Lars Henrik","family":"Jensen","sequence":"additional","affiliation":[{"name":"Department of Oncology, Vejle Hospital, University Hospital of Southern Denmark, 7100 Vejle, Denmark"},{"name":"Department of Oncology, Institute of Regional Health Research, University of Southern Denmark, 7100 Vejle, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,4]]},"reference":[{"key":"ref_1","first-page":"7","article-title":"Cancer Statistics","volume":"71","author":"Siegel","year":"2021","journal-title":"CA Cancer J. 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