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Currently, effective biomarkers to predict and improve chemotherapy resistance in ICC are lacking. Here, it is reported that a long non\u2010coding RNA (lncRNA),\n                    <jats:italic>PAX8\u2010AS1<\/jats:italic>\n                    , reduces the efficacy of standard chemotherapeutic drugs. Mechanistically,\n                    <jats:italic>PAX8\u2010AS1<\/jats:italic>\n                    activates NRF2 by binding to p62, thereby promoting GPX4 transcription, and stabilizes\n                    <jats:italic>GPX4<\/jats:italic>\n                    mRNA through interaction with IGF2BP3. The\n                    <jats:italic>PAX8\u2010AS1<\/jats:italic>\n                    \/GPX4 axis inhibits ferroptosis and promotes resistance to gemcitabine and cisplatin. In preclinical models, the combination of the GPX4 inhibitor JKE\u20101674 with gemcitabine and cisplatin exhibits superior antitumor efficacy. These findings suggest a promising therapeutic strategy to improve chemotherapy efficacy in advanced ICC.\n                  <\/jats:p>","DOI":"10.1002\/advs.202501042","type":"journal-article","created":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T07:50:18Z","timestamp":1747727418000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Targeting GPX4 to Induce Ferroptosis Overcomes Chemoresistance Mediated by the\n                    <i>PAX8\u2010AS1<\/i>\n                    \/GPX4 Axis in Intrahepatic Cholangiocarcinoma"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1770-6208","authenticated-orcid":false,"given":"Zhi\u2010Wen","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Hepatic Surgery Fudan University Shanghai Cancer Center Shanghai Medical College Fudan University Shanghai 200032 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