{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T07:23:25Z","timestamp":1787729005745,"version":"build-2784847793"},"reference-count":68,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp;amp; Translational Med"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Non\u2010small cell lung cancer (NSCLC) remains a leading cause of global cancer mortality. Increasing evidence implicates aberrant cholesterol metabolic reprogramming as a key facilitator of tumour malignancy; however, the mechanistic connections between lipoprotein metabolism and NSCLC pathogenesis remain elusive. Here, we investigate the unrecognised oncogenic role of cholesteryl ester transfer protein (CETP), a central lipid exchange mediator.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Serum lipid profiles from 151 NSCLC patients were analysed, and CETP mRNA expression level was evaluated in normal lung (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a047) and NSCLC tissue (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a054) and paired NSCLC tissue microarrays (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a0113). Integrated ChIP\u2010seq\/RNA\u2010seq analyses, ChIP\u2013qPCR, dual\u2010luciferase reporter and ubiquitination assays were performed to investigate CTBP1\u2010mediated CETP transcription. Functional studies in NSCLC cells, xenograft models and eight patient\u2010derived organoids evaluated the role of the CTBP1\u2013CETP axis in lipid remodelling, ferroptosis and the therapeutic efficacy of obicetrapib alone or combined with RSL3.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      CETP was significantly up\u2010regulated in NSCLC tissues and predicted poor overall survival in both LUAD (HR\u00a0=\u00a01.46, 95% CI 1.13\u20131.87,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a0.0033) and LUSC (HR\u00a0=\u00a01.51, 95% CI 1.12\u20132.01,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a0.0067). CTBP1 activated CETP transcription, and CTBP1 ubiquitination further enhanced its transcriptional activity. The CTBP1\u2013CETP axis promoted ferroptosis resistance by lipid accumulation. Obicetrapib phenocopied CETP depletion and synergised with RSL3 to inhibit tumour growth in NSCLC cells, xenografts and patient\u2010derived organoids.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study delineates a novel CTBP1\u2013CETP\u2013lipid droplet\u2013MAPK signalling cascade that couples metabolic rewiring with ferroptosis evasion. These insights establish the CTBP1\u2013CETP axis as a critical cell fate determinant, positioning pharmacological CETP inhibition (e.g., obicetrapib) as a translatable therapeutic vulnerability in lipid\u2010dependent, ferroptosis\u2010resistant NSCLC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ctm2.70749","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T05:44:23Z","timestamp":1785217463000},"source":"Crossref","is-referenced-by-count":0,"title":["Targeting the CTBP1\u2013CETP axis overcomes ferroptosis resistance in non\u2010small cell lung cancer by altering lipid accumulation"],"prefix":"10.1002","volume":"16","author":[{"given":"Yanjie","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Oncology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology  Wuhan 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