{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T09:50:59Z","timestamp":1791539459408,"version":"4.3.4"},"reference-count":111,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T00:00:00Z","timestamp":1789862400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T00:00:00Z","timestamp":1789862400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Drug Development Research"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Statins inhibit 3\u2010hydroxy\u20103\u2010methylglutaryl\u2010coenzyme A reductase (HMGCR) and reduce flux through the mevalonate pathway, which supplies both cholesterol and the non\u2010sterol isoprenoids required for prenylation of small GTPases. Because this pathway is frequently activated in cancer, statins have become one of the most intensively studied candidates for oncological drug repurposing. Preclinical work indicates that statins can lower the threshold for apoptosis, modulate autophagy in either a pro\u2010death or a cytoprotective direction, induce pyroptosis, and sensitize cells to ferroptosis, while also acting on CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, macrophages, dendritic cells, and cancer\u2010associated fibroblasts within the tumor microenvironment. Clinical evidence, however, remains discordant with the strength of these mechanistic claims: favorable observational associations are susceptible to immortal\u2010time bias, healthy\u2010user bias, and confounding by indication, and randomized trials have been largely neutral for tumor\u2010directed endpoints. This narrative review appraises the mechanistic, preclinical, and clinical literature using an explicit five\u2010tier evidence hierarchy, and treats two constraints as analytical tools rather than closing caveats: the pharmacological heterogeneity of individual statins, and the one\u2010to\u2010two order\u2010of\u2010magnitude gap between concentrations used in cancer\u2010cell experiments and free drug concentrations achievable in patients. We conclude that statins are biologically plausible but clinically unproven anticancer agents whose evaluation should proceed through biomarker\u2010selected, pharmacodynamically validated combination trials rather than unselected add\u2010on designs.\n                  <\/jats:p>","DOI":"10.1002\/ddr.70388","type":"journal-article","created":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T08:59:48Z","timestamp":1789894788000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Statins as Repurposed Anticancer Agents: Regulated Cell Death, the Tumor Immune Microenvironment, and the Translational Evidence Gap"],"prefix":"10.1002","volume":"87","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-2745-9806","authenticated-orcid":false,"given":"Xu","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Oncology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's 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