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Due to its aggressive nature, CCA is considered a rare and highly advanced form of malignancy. This research is detailed around which role does ferroptosis play in CCA and what impact does it have on CCA progression as well as on treatment resistance. A systematic assessment of previously published works was conducted to understand the cellular mechanisms of ferroptosis, the pertinent biological networks, and its possible therapeutic targets. During the research, we discovered that the sensitivity of CCA cells to ferroptosis associated cell death is increased because they have dysregulated iron metabolism and uncontrolled lipid peroxidation. Sensitivity to ferroptosis is regulated by important proteins such as acyl\u2010CoA synthetase long\u2010chain family member 4 (ACSL4) and solute carrier family 7 member 11 (SLC7A11). In addition, the ferroptosis inducers erastin and RSL3 are capable of enhancing the efficacy of traditional therapies and seeking solutions for the chemoresistance problem. The hurdles to be overcome are finding reliable biomarkers for the prediction of ferroptosis sensitivity and designing targeted delivery systems for minimal off\u2010target effects. Clinically, these techniques offer novel concepts in the treatment of CCA, making further research key to these conclusions being adopted in practice.<\/jats:p>","DOI":"10.1002\/ddr.70237","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T09:51:12Z","timestamp":1769766672000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Ferroptosis in Cholangiocarcinoma Therapy: Molecular Mechanisms, Pharmacological Modulation and Opportunities for Drug Development"],"prefix":"10.1002","volume":"87","author":[{"given":"Hafsa","family":"Athar","sequence":"first","affiliation":[{"name":"National University of Science and Technology (NUST) Islamabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabahat","family":"Zulfiqar","sequence":"additional","affiliation":[{"name":"School of Medicine (NUSOM) Nazarbayev University Astana Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arslan","family":"Ali","sequence":"additional","affiliation":[{"name":"National University of Science and Technology (NUST) Islamabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Armaghan","sequence":"additional","affiliation":[{"name":"National University of Science and Technology (NUST) Islamabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9946-9057","authenticated-orcid":false,"given":"Khushbukhat","family":"Khan","sequence":"additional","affiliation":[{"name":"Clinical and Preclinical Studies Unit Lahore Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3639-0528","authenticated-orcid":false,"given":"William N.","family":"Setzer","sequence":"additional","affiliation":[{"name":"Aromatic Plant Research Center Lehi Utah USA"},{"name":"Department of Chemistry University of Alabama in Huntsville Huntsville Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7301-8151","authenticated-orcid":false,"given":"Javad","family":"Sharifi\u2010Rad","sequence":"additional","affiliation":[{"name":"Universidad Esp\u00edritu Santo Samborond\u00f3n Ecuador"},{"name":"Department of Medicine, College of Medicine Korea University Seoul Republic of Korea"},{"name":"Centro de Estudios Tecnol\u00f3gicos y Universitarios del Golfo Veracruz Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1523-9116","authenticated-orcid":false,"given":"Daniela","family":"Calina","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy University of Medicine and Pharmacy of Craiova Craiova Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,30]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.14100"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-022-01998-x"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines12092091"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2016.51"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-020-0310-z"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0302050"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41585-024-00869-9"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21144908"},{"key":"e_1_2_13_10_1","first-page":"4908","volume":"21","author":"Capelletti M. 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