{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T02:40:27Z","timestamp":1792809627054,"version":"4.5.0"},"reference-count":95,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:00:00Z","timestamp":1792627200000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001322","name":"South African Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Gynaecological malignancies account for over 1.4 million new diagnoses, with outcomes constrained by late\u2010stage presentation and chemoresistance. Dysregulated redox homeostasis is a hallmark of tumourigenesis. Tumour cells maintain elevated basal reactive oxygen species (ROS), which support proliferative signalling but may also increase susceptibility to further oxidative stress. Vitamin D, acting through the vitamin D receptor (VDR), has antiproliferative and pro\u2010apoptotic effects across cancer models, but its ability to amplify ROS beyond an apoptotic threshold in gynaecological malignancies remains unresolved. We conducted a narrative literature search of PubMed\/MEDLINE,\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                    and the Surveillance, Epidemiology and End Results databases, using terms related to vitamin D and its metabolites, ROS\/oxidative stress, apoptosis and gynaecological malignancies. Preclinical evidence indicates that calcitriol and related compounds can induce ROS\u2010mediated mitochondrial apoptosis, modulate autophagy and arrest the cell cycle. In ovarian cancer, non\u2010HGSOC cell data suggest that mutant TP53 may alter calcitriol responses, requiring validation in high\u2010grade serous ovarian carcinoma models. In cervical cancer, calcitriol radiosensitises human papillomavirus\u2010positive cell lines through autophagy suppression, whilst an in\u00a0vivo calcitriol\u2010cisplatin study reported improved survival. In endometrial cancer, thioredoxin\u2010interacting protein induction is a candidate mechanism for selective ROS\u2010mediated apoptosis, although this remains context\u2010dependent. Clinical evidence is heterogeneous: higher 25\u2010hydroxyvitamin D status has shown modest inverse associations with ovarian cancer mortality; small trials report regression or reduced recurrence of cervical intraepithelial neoplasia; no randomised controlled trial evidence supports efficacy in invasive cervical cancer; and associations with endometrial cancer incidence are largely null. Current evidence does not support vitamin D supplementation as an oncology\u2010specific intervention. Future research should prioritise biomarker\u2010stratified trials incorporating VDR genotype, CYP24A1 profiling, pre\u2010specified 25(OH)D targets and pharmacokinetically informed dosing.\n                  <\/jats:p>","DOI":"10.1002\/cam4.72292","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T12:06:17Z","timestamp":1792670777000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring Vitamin D Metabolism in Gynaecological Malignancies: Redox\u2010Dependent and Redox\u2010Independent Anticancer Mechanisms From Preclinical Models to Clinical Evidence"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-8858-8633","authenticated-orcid":false,"given":"Hoi Ching Cherry","family":"Chan","sequence":"first","affiliation":[{"name":"Department of Chemical Pathology, Faculty of Health Sciences University of Pretoria  Pretoria Gauteng South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7050-4974","authenticated-orcid":false,"given":"Sachin","family":"Bhoora","sequence":"additional","affiliation":[{"name":"Vitamin D Cancer Group, Division of Chemical Pathology, Department of Pathology University of Cape Town  Cape Town South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3652-1193","authenticated-orcid":false,"given":"Esther","family":"Zhou","sequence":"additional","affiliation":[{"name":"Vitamin D Cancer Group, Division of Chemical Pathology, Department of Pathology University of Cape Town  Cape Town South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3953-227X","authenticated-orcid":false,"given":"Sumari","family":"Marais","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Health Sciences University of Pretoria  Pretoria Gauteng South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1570-3959","authenticated-orcid":false,"given":"Rivak","family":"Punchoo","sequence":"additional","affiliation":[{"name":"Department of Chemical Pathology, Faculty of Health Sciences University of Pretoria  Pretoria Gauteng South Africa"},{"name":"Vitamin D Cancer Group, Division of Chemical Pathology, Department of Pathology University of Cape Town  Cape Town South Africa"},{"name":"Division of Chemical Pathology, Department of Pathology University of Cape Town  Cape Town South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,22]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045\u2010025\u201001660\u2010y"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2024.104434"},{"key":"e_1_2_13_5_1","volume-title":"Endotext","author":"Bikle D. 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