{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T23:06:59Z","timestamp":1783984019030,"version":"3.55.0"},"reference-count":38,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100008886","name":"Princess Takamatsu Cancer Research Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008886","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Metastatic prostate cancer often develops resistance to second\u2010generation androgen receptor pathway inhibitors (ARPIs) such as enzalutamide and darolutamide, limiting their long\u2010term efficacy. In this study, we applied the high\u2010precision absolute quantitative proteomics platform iMPAQT to comprehensively profile protein expression changes in multiple prostate cancer cell lines and their ARPI\u2010resistant derivatives. Our analysis revealed consistent dysregulation of ferroptosis suppressor pathway alongside elevated phosphorylation of AMPK\u03b1 signaling in resistant cells. While antiandrogen treatment increased lipid peroxidation in parental cells, resistant cells adapted by upregulating key ferroptosis\u2010regulating proteins including FTH1 and GPX4, thereby evading ferroptosis. Functional assays demonstrated that the GPX4 inhibitor RSL3 selectively suppressed proliferation of resistant cells more potently than parental cells. Moreover, combination treatment with AMPK\u03b1 inhibitors enhanced the anti\u2010proliferative effect of RSL3. These findings suggest that ferroptosis suppression is a critical mechanism underpinning resistance to ARPIs in prostate cancer. Targeting pathways involved in ferroptosis regulation in combination with AMPK\u03b1 inhibitors holds promise for overcoming therapeutic resistance and improving patient outcomes.<\/jats:p>","DOI":"10.1111\/cas.70477","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T22:55:19Z","timestamp":1783983319000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Proteomic Analysis Reveals\n                    <scp>AMPK\u03b1<\/scp>\n                    \u2010Mediated Antiandrogen Resistance via Ferroptosis Suppression in Prostate Cancer"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3306-4858","authenticated-orcid":false,"given":"Masaki","family":"Shiota","sequence":"first","affiliation":[{"name":"Department of Urology, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1631-4720","authenticated-orcid":false,"given":"Tokiyoshi","family":"Tanegashima","sequence":"additional","affiliation":[{"name":"Department of Urology, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiko","family":"Hajime","sequence":"additional","affiliation":[{"name":"Department of Urology, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miho","family":"Ushijima","sequence":"additional","affiliation":[{"name":"Department of Urology, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3533-6781","authenticated-orcid":false,"given":"Shigehiro","family":"Tsukahara","sequence":"additional","affiliation":[{"name":"Department of Urology, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shohei","family":"Nagakawa","sequence":"additional","affiliation":[{"name":"Department of Urology, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Urology, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Department of Urology, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3312-9930","authenticated-orcid":false,"given":"Masatoshi","family":"Eto","sequence":"additional","affiliation":[{"name":"Department of Urology, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,13]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1007\/s11604-025-01816-3","article-title":"Recent Advances in Drug Treatment for Prostate Cancer","volume":"43","author":"Suzuki K.","year":"2025","journal-title":"Japanese Journal of Radiology"},{"key":"e_1_2_13_3_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.ctarc.2022.100606","article-title":"Current Status and Future Perspective on the Management of Metastatic Castration\u2010Sensitive Prostate Cancer","volume":"32","author":"Blas 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