{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T22:00:39Z","timestamp":1790287239844,"version":"4.1.0"},"posted":{"date-parts":[[2026,3,27]]},"group-title":"Cancer Biology","reference-count":60,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["PCF-22CHAL05"],"award-info":[{"award-number":["PCF-22CHAL05"]}],"id":[{"id":"https:\/\/ror.org\/01npwtv09","id-type":"ROR","asserted-by":"publisher"}]},{"award":["25YOUN19"],"award-info":[{"award-number":["25YOUN19"]}],"id":[{"id":"https:\/\/ror.org\/01npwtv09","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Department of Defense","award":["W81XWH-19-1-0566"],"award-info":[{"award-number":["W81XWH-19-1-0566"]}]},{"name":"Department of Defense","award":["HT9425-25-1-0385"],"award-info":[{"award-number":["HT9425-25-1-0385"]}]},{"name":"National Institute of Health","award":["PO1-CA-265768"],"award-info":[{"award-number":["PO1-CA-265768"]}]},{"name":"National Institute of Health","award":["P50CA21104"],"award-info":[{"award-number":["P50CA21104"]}]},{"name":"National Institute of Health","award":["R01-CA-234162"],"award-info":[{"award-number":["R01-CA-234162"]}]},{"name":"American Cancer Society","award":["PF-24-1318851-01-MM"],"award-info":[{"award-number":["PF-24-1318851-01-MM"]}],"id":[{"id":"https:\/\/ror.org\/02e463172","id-type":"ROR","asserted-by":"crossref"}]},{"name":"American Italian Cancer Foundation Postdoctoral Fellowships","award":["Ezio, Maria e Bianca Panciera"],"award-info":[{"award-number":["Ezio, Maria e Bianca Panciera"]}]},{"name":"Research Foundation Flanders","award":["G032525N"],"award-info":[{"award-number":["G032525N"]}]},{"name":"Belgian Foundation Against Cancer","award":["F\/2020\/1417"],"award-info":[{"award-number":["F\/2020\/1417"]}]},{"name":"Belgian Foundation Against Cancer","award":["Kom Op Tegen Kanker (Stand Up to Cancer)"],"award-info":[{"award-number":["Kom Op Tegen Kanker (Stand Up to Cancer)"]}]},{"name":"Belgian Foundation Against Cancer","award":["Leuven Future Fund LISCO-BIOMED"],"award-info":[{"award-number":["Leuven Future Fund LISCO-BIOMED"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Prostate cancer progression is characterized by dysregulated lipid metabolism, with activation of fatty acid synthase (FASN), the rate-limiting step in\n                  <jats:italic>de novo<\/jats:italic>\n                  lipogenesis (DNL), resulting in significant accumulation of saturated lipids. Here, we show that pharmacologic FASN inhibition creates a metabolic state that increases reliance on exogenous polyunsaturated fatty acids (PUFAs). Inhibition of FASN profoundly alters membrane phospholipid composition, driving compensatory incorporation of PUFAs into membrane phospholipids, thus increasing susceptibility to lipid peroxidation and oxidative damage. Combined FASN inhibition and PUFA exposure induce mitochondrial hyperpolarization and enhance lipid peroxidation in both hormone-sensitive and castration-resistant prostate cancer models, resulting in increased reactive oxygen species production, ferroptosis, as well as apoptosis. Marked inhibition of growth in castration-resistant human and murine prostate cancer organoids is achieved\n                  <jats:italic>ex vivo<\/jats:italic>\n                  . In genetically engineered, DNL-reliant Hi-Myc mice, a diet enriched in PUFAs significantly inhibited invasive carcinoma compared to a saturated fat-enriched diet. Thus, environmental PUFAs modulate and enhance the therapeutic efficacy of FASN-targeted strategies. These findings set the stage for pharmacologic and dietary intervention in prostate cancer patients.\n                <\/jats:p>","DOI":"10.64898\/2026.03.25.714193","type":"posted-content","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T21:10:29Z","timestamp":1774645829000},"source":"Crossref","is-referenced-by-count":0,"title":["Suppression of de novo lipogenesis and dietary PUFA supplementation inhibit prostate cancer progression"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7239-8324","authenticated-orcid":false,"given":"Silvia D.","family":"Rodrigues","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6785-6933","authenticated-orcid":false,"given":"Caroline","family":"Fidalgo Ribeiro","sequence":"additional","affiliation":[{"name":"Department of Pathology 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