{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T11:18:13Z","timestamp":1783423093924,"version":"3.54.6"},"reference-count":13,"publisher":"IMR Press","issue":"6","license":[{"start":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T00:00:00Z","timestamp":1781222400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"High-Level Talent Introduction Funds from the First Hospital of Lanzhou University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Front. Biosci. (Landmark Ed)"],"abstract":"<jats:p>Pancreatic ductal adenocarcinoma (PDAC) remains a lethal malignancy largely because its early stages evade detection. Two recent studies by Hennequart et al. and Radyk et al. (2026, Nature Metabolism) agree on the following concept: pancreatic acinar cells must maintain a narrow \u201credox precipice\u201d during acinar-to-ductal metaplasia (ADM), the initial reversible precursor of PDAC. Redundant nicotinamide adenine dinucleotide phosphate-generating systems-mitochondrial aldehyde dehydrogenase 1 family member L2 and cytosolic glucose-6-phosphate dehydrogenase\/malic enzyme 1-generally regulate reactive oxygen species within a range that facilitates pro-survival signaling without inducing cell death. Disruption of these systems promotes ADM formation and pancreatic intraepithelial neoplasia, whereas antioxidant treatment inhibits progression. This Opinion integrates these findings within a broader framework of metabolic gatekeeping, discusses how the redox precipice interacts with epigenetic reprogramming and immune evasion, and proposes that the transition from redox balance to addiction results in stage-specific vulnerabilities. Circulating formate emerges as a promising biomarker for early detection, and we highlight key unanswered questions, including whether similar principles apply to other metaplasia-driven malignancies.<\/jats:p>","DOI":"10.31083\/fbl52694","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T10:50:51Z","timestamp":1783421451000},"source":"Crossref","is-referenced-by-count":0,"title":["Navigating the Redox Precipice: Metabolic Gatekeeping as a Therapeutic Window in Pancreatic Precancer"],"prefix":"10.31083","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-2266-6317","authenticated-orcid":true,"given":"Dong-Yang","family":"Qi","sequence":"first","affiliation":[{"name":"Institute of Cancer Neuroscience, Medical Frontier Innovation Research Center, The First Hospital of Lanzhou University, The First Clinical Medical College of Lanzhou University, 730000 Lanzhou, Gansu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8011-2405","authenticated-orcid":true,"given":"Wei-Lin","family":"Jin","sequence":"additional","affiliation":[{"name":"Institute of Cancer Neuroscience, Medical Frontier Innovation Research Center, The First Hospital of Lanzhou University, The First Clinical Medical College of Lanzhou University, 730000 Lanzhou, Gansu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2026,6,12]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Carpenter ES, Elhossiny AM, Kadiyala P, Li J, McGue J, Griffith BD, et al. Analysis of Donor Pancreata Defines the Transcriptomic Signature and Microenvironment of Early Neoplastic Lesions. Cancer Discovery. 2023; 13: 1324\u20131345.","DOI":"10.1158\/2159-8290.CD-23-0013"},{"key":"ref2","doi-asserted-by":"publisher","unstructured":"Halbrook CJ, Lyssiotis CA, Pasca di Magliano M, Maitra A. Pancreatic cancer: Advances and challenges. Cell. 2023; 186: 1729\u20131754.","DOI":"10.1016\/j.cell.2023.02.014"},{"key":"ref3","doi-asserted-by":"publisher","unstructured":"Hennequart M, Mervant L, Stockis J, Coomes J, Zarou MM, Gerard L, et al. ALDH1L2 regulates reactive oxygen species and acinar-to-ductal metaplasia in the pancreas. Nature Metabolism. 2026; 8: 810\u2013823.","DOI":"10.1038\/s42255-026-01456-5"},{"key":"ref4","doi-asserted-by":"publisher","unstructured":"Radyk MD, Nelson BS, Ruckert MT, Halbrook CJ, Shan M, Alektiar JM, et al. NADPH-producing enzymes restrict the formation of pancreatic precancerous lesions. 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