{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T13:25:20Z","timestamp":1786973120234,"version":"build-2736575974"},"reference-count":48,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"abstract":"<jats:p>\n                    Host metabolic changes in response to drug treatment may shape individual pharmacological outcomes. This study aims to identify serum metabolomics signatures potentially associated with individual responses to enzalutamide treatment in metastatic castrate\u2010resistant prostate cancer (mCRPC) patients. Targeted metabolomic profiles in serum collected from 18 mCRPC patients treated with 160\u2009mg\/day of enzalutamide were measured at baseline, after 3\u2009months of treatment, and until disease progression by a validated liquid chromatography tandem mass spectrometry analytical platform. The difference in the serum metabolomic profiles during enzalutamide treatment between good and poor responders was investigated by both multivariate and univariate statistical analysis. Primary mouse hepatocytes and Caco\u20102 cell models were employed to gain mechanistic insights into the most relevant changes detected. Enzalutamide induced a significant and sustained increase in several amino acids, with taurine displaying the most significant change. The\n                    <jats:italic>in vitro<\/jats:italic>\n                    data suggest that enzalutamide\u2010induced elevation of systemic taurine results from both increased intestinal absorption and decreased hepatic extraction. Finally, serum metabolomic changes observed after 3 months of treatment were found to be significantly associated with the pharmacological response. This hypothesis\u2010generating study reveals that enzalutamide significantly alters the host serum metabolome, inducing changes that correlate with therapeutic response over time. These results highlight the importance of host\u2010drug metabolic interactions during androgen receptor inhibitor treatment and, although further validation is required, they support the hypothesis that metabolic profiling could eventually aid in the personalized management of enzalutamide therapy.\n                  <\/jats:p>","DOI":"10.1002\/cpt.70442","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T12:37:22Z","timestamp":1786970242000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Enzalutamide\u2010Induced Host Metabolic Reprogramming Is Associated with Treatment Outcomes in Patients with Castration\u2010Resistant Prostate Cancer: A Hypothesis\u2010Generating Study"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3619-7709","authenticated-orcid":false,"given":"Giuseppe","family":"Corona","sequence":"first","affiliation":[{"name":"Immunopathology and Cancer Biomarkers Unit Centro di Riferimento Oncologico di Aviano (CRO), IRCCS  Aviano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0209-5600","authenticated-orcid":false,"given":"Michele","family":"Visentin","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Toxicology University Hospital Zurich, University of Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia Leonie","family":"Samodelov","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Toxicology University Hospital Zurich, University of Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Maines","sequence":"additional","affiliation":[{"name":"Medical Oncology Department Santa Chiara Hospital, APSS  Trento Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orazio","family":"Caffo","sequence":"additional","affiliation":[{"name":"Medical Oncology Department Santa Chiara Hospital, APSS  Trento Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianmaria","family":"Miolo","sequence":"additional","affiliation":[{"name":"Medical Oncology and Cancer Prevention Unit Centro di Riferimento Oncologico di Aviano (CRO), IRCCS  Aviano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,17]]},"reference":[{"key":"e_1_2_12_1_1","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1007\/s11864-024-01215-2","article-title":"Metastatic castration\u2010resistant prostate cancer: advances in treatment and symptom management","volume":"25","author":"Kulasegaran T.","year":"2024","journal-title":"Curr. Treat. Options Oncol."},{"key":"e_1_2_12_2_1","doi-asserted-by":"crossref","DOI":"10.1001\/jamanetworkopen.2024.28444","article-title":"Abiraterone or enzalutamide for patients with metastatic castration\u2010resistant prostate cancer","volume":"7","author":"La J.","year":"2024","journal-title":"JAMA Netw. Open"},{"key":"e_1_2_12_3_1","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1080\/14737140.2024.2405103","article-title":"Current uses and resistance mechanisms of enzalutamide in prostate cancer treatment","volume":"24","author":"Miller C.D.","year":"2024","journal-title":"Expert Rev. Anticancer Ther."},{"key":"e_1_2_12_4_1","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1056\/NEJMoa1315815","article-title":"AR\u2010V7 and resistance to enzalutamide and abiraterone in prostate cancer","volume":"371","author":"Antonarakis E.S.","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"e_1_2_12_5_1","doi-asserted-by":"crossref","DOI":"10.1172\/JCI168649","article-title":"Androgen receptor splice variants drive castration\u2010resistant prostate cancer metastasis by activating distinct transcriptional programs","volume":"134","author":"Han D.","year":"2024","journal-title":"J. Clin. Invest."},{"key":"e_1_2_12_6_1","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1038\/s41568-024-00786-4","article-title":"Metabolic interplays between the tumour and the host shape the tumour macroenvironment","volume":"25","author":"Altea\u2010Manzano P.","year":"2025","journal-title":"Nat. Rev. Cancer"},{"issue":"2","key":"e_1_2_12_7_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2025.115234","article-title":"Emerging insights into the impact of systemic metabolic changes on tumor\u2010immune interactions","volume":"44","author":"Cote A.L.","year":"2025","journal-title":"Cell Rep."},{"key":"e_1_2_12_8_1","doi-asserted-by":"crossref","first-page":"E767","DOI":"10.1152\/ajpendo.00584.2010","article-title":"Increased adiposity in DNA binding\u2010dependent androgen receptor knockout male mice associated with decreased voluntary activity and not insulin resistance","volume":"301","author":"Rana K.","year":"2011","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"e_1_2_12_9_1","doi-asserted-by":"crossref","first-page":"1717","DOI":"10.2337\/diabetes.54.6.1717","article-title":"Insulin and leptin resistance with hyperleptinemia in mice lacking androgen receptor","volume":"54","author":"Lin H.Y.","year":"2005","journal-title":"Diabetes"},{"key":"e_1_2_12_10_1","doi-asserted-by":"crossref","DOI":"10.3390\/cancers16111991","article-title":"Metabolic response to androgen deprivation therapy of prostate cancer","volume":"16","author":"Chen Y.","year":"2024","journal-title":"Cancers (Basel)."},{"key":"e_1_2_12_11_1","doi-asserted-by":"crossref","first-page":"14328","DOI":"10.1074\/jbc.RA118.004442","article-title":"Inhibition of cholesterol biosynthesis overcomes enzalutamide resistance in castration\u2010resistant prostate cancer (CRPC)","volume":"293","author":"Kong Y.","year":"2018","journal-title":"J. Biol. Chem."},{"key":"e_1_2_12_12_1","doi-asserted-by":"crossref","DOI":"10.3390\/ijms24020910","article-title":"Emerging hallmarks of metabolic reprogramming in prostate cancer","volume":"24","author":"Lasorsa F.","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/cas.15016"},{"key":"e_1_2_12_14_1","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.canlet.2020.05.007","article-title":"GLUT1 is an AR target contributing to tumor growth and glycolysis in castration\u2010resistant and enzalutamide\u2010resistant prostate cancers","volume":"485","author":"Wang J.","year":"2020","journal-title":"Cancer Lett."},{"key":"e_1_2_12_15_1","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1038\/nrd.2016.32","article-title":"Emerging applications of metabolomics in drug discovery and precision medicine","volume":"15","author":"Wishart D.S.","year":"2016","journal-title":"Nat. Rev. Drug Discov."},{"key":"e_1_2_12_16_1","doi-asserted-by":"crossref","DOI":"10.3390\/cancers17243993","article-title":"Metabolomic insights into prostate cancer treatment and relapse","volume":"17","author":"Lundquist K.","year":"2025","journal-title":"Cancer"},{"key":"e_1_2_12_17_1","doi-asserted-by":"crossref","first-page":"G295","DOI":"10.1152\/ajpgi.00076.2022","article-title":"Testosterone enhances taurine synthesis by upregulating androgen receptor and cysteine sulfinic acid decarboxylase expressions in male mouse liver","volume":"324","author":"Zhang D.","year":"2023","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"e_1_2_12_18_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/0471140856.tx2006s47","article-title":"Caco\u20102 cells as a model for intestinal absorption","volume":"47","author":"Angelis I.D.","year":"2011","journal-title":"Curr. Protoc. Toxicol."},{"key":"e_1_2_12_19_1","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1124\/mol.116.103390","article-title":"Role of multidrug resistance protein 3 in antifungal\u2010induced cholestasis","volume":"90","author":"Mahdi Z.M.","year":"2016","journal-title":"Mol. Pharmacol."},{"key":"e_1_2_12_20_1","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1111\/bju.12898","article-title":"Enzalutamide in European and north American men participating in the AFFIRM trial","volume":"115","author":"Merseburger A.S.","year":"2015","journal-title":"BJU Int."},{"key":"e_1_2_12_21_1","doi-asserted-by":"crossref","first-page":"676","DOI":"10.3181\/00379727-100-24741","article-title":"Dietary glycine and taurine on bile acid conjugation in man; bile acids and steroids 75","volume":"100","author":"Sjovall J.","year":"1959","journal-title":"Proc. Soc. Exp. Biol. Med."},{"key":"e_1_2_12_22_1","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1152\/physrev.1992.72.1.101","article-title":"Physiological actions of taurine","volume":"72","author":"Huxtable R.J.","year":"1992","journal-title":"Physiol. Rev."},{"key":"e_1_2_12_23_1","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1007\/s00726-012-1386-8","article-title":"Taurine homeostasis requires de novo synthesis via cysteine sulfinic acid decarboxylase during zebrafish early embryogenesis","volume":"44","author":"Chang Y.C.","year":"2013","journal-title":"Amino Acids"},{"key":"e_1_2_12_24_1","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1124\/dmd.119.089995","article-title":"Flavin\u2010containing monooxygenase 1 catalyzes the production of taurine from Hypotaurine","volume":"48","author":"Veeravalli S.","year":"2020","journal-title":"Drug Metab. Dispos."},{"key":"e_1_2_12_25_1","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1093\/jn\/84.3.220","article-title":"Vitamin B6 depletion in man: urinary taurine and sulfate excretion and nitrogen balance","volume":"84","author":"Swan P.","year":"1964","journal-title":"J. Nutr."},{"key":"e_1_2_12_26_1","doi-asserted-by":"crossref","DOI":"10.3390\/metabo13070824","article-title":"Upregulation of taurine biosynthesis and bile acid conjugation with taurine through FXR in a mouse model with human\u2010like bile acid composition","volume":"13","author":"Miyazaki T.","year":"2023","journal-title":"Metabolites."},{"key":"e_1_2_12_27_1","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/0005-2736(80)90272-2","article-title":"Taurine transport by rat hepatocytes in primary culture","volume":"598","author":"Hardison W.G.","year":"1980","journal-title":"Biochim. Biophys. Acta"},{"key":"e_1_2_12_28_1","doi-asserted-by":"crossref","first-page":"G291\u20107","DOI":"10.1152\/ajpgi.00388.2011","article-title":"Involvement of \u03b3\u2010aminobutyric acid transporter 2 in the hepatic uptake of taurine in rats","volume":"303","author":"Ikeda S.","year":"2012","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"issue":"4","key":"e_1_2_12_29_1","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1113\/jphysiol.2008.164228","article-title":"Taurine uptake across the human intestinal brush\u2010border membrane is via two transporters: H+\u2010coupled PAT1 (SLC36A1) and Na+\u2212 and Cl(\u2212)\u2010dependent TauT (SLC6A6)","volume":"587","author":"Anderson C.M.","year":"2009","journal-title":"J.\u00a0Physiol."},{"issue":"2","key":"e_1_2_12_30_1","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1113\/jphysiol.2002.026500","article-title":"Structure, function and immunolocalization of a proton\u2010coupled amino acid transporter (hPAT1) in the human\u00a0intestinal cell line Caco\u20102","volume":"546","author":"Chen Z.","year":"2003","journal-title":"J. Physiol."},{"key":"e_1_2_12_31_1","doi-asserted-by":"crossref","DOI":"10.1007\/s00345-024-05280-y","article-title":"Enzalutamide versus abiraterone acetate in the development of new\u2010onset or worsening type 2 diabetes mellitus in patients with metastatic castration\u2010resistant prostate cancer: EVADE study","volume":"42","author":"Bahl A.","year":"2024","journal-title":"World J. Urol."},{"key":"e_1_2_12_32_1","doi-asserted-by":"crossref","DOI":"10.1186\/s13046-025-03600-7","article-title":"STARD4 suppresses tumorigenesis and attenuates enzalutamide resistance via lipid metabolic reprogramming and AR stabilization in prostate cancer","volume":"44","author":"Zhang Y.","year":"2025","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"e_1_2_12_33_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.canlet.2025.217808","article-title":"Ketogenesis instigates immune suppression in enzalutamide resistant prostate cancer via OTUD7B \u03b2\u2010hydroxybutyrylation","volume":"625","author":"Jiang H.","year":"2025","journal-title":"Cancer Lett."},{"key":"e_1_2_12_34_1","doi-asserted-by":"crossref","DOI":"10.1186\/s40170-020-00217-6","article-title":"Therapy\u2010induced lipid uptake and remodeling underpin ferroptosis hypersensitivity in prostate cancer","volume":"8","author":"Tousignant K.D.","year":"2020","journal-title":"Cancer Metab."},{"key":"e_1_2_12_35_1","doi-asserted-by":"crossref","first-page":"2347","DOI":"10.1038\/s41388-023-02756-w","article-title":"Critical role of antioxidant programs in enzalutamide\u2010resistant prostate cancer","volume":"42","author":"Blatt E.B.","year":"2023","journal-title":"Oncogene"},{"key":"e_1_2_12_36_1","first-page":"192","article-title":"The role of glutamine metabolism in castration\u2010resistant prostate cancer","volume":"25","author":"Zhao B.","year":"2023","journal-title":"Asian J. Androl."},{"key":"e_1_2_12_37_1","doi-asserted-by":"crossref","DOI":"10.3389\/fonc.2024.1286896","article-title":"Metabolomics analysis reveals novel serum metabolite alterations in cancer cachexia","volume":"14","author":"More T.H.","year":"2024","journal-title":"Front. Oncol."},{"key":"e_1_2_12_38_1","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1111\/iju.13473","article-title":"Metabolic changes in patients with prostate cancer during androgen deprivation therapy","volume":"25","author":"Mitsuzuka K.","year":"2018","journal-title":"Int. J. Urol."},{"key":"e_1_2_12_39_1","doi-asserted-by":"crossref","first-page":"R371","DOI":"10.1530\/ERC-14-0172","article-title":"Muscle and bone effects of androgen deprivation therapy: current and emerging therapies","volume":"21","author":"Cheung A.S.","year":"2014","journal-title":"Endocr. Relat. Cancer"},{"key":"e_1_2_12_40_1","doi-asserted-by":"crossref","DOI":"10.3390\/cells11152337","article-title":"Versatile triad Alliance: bile acid, taurine and microbiota","volume":"11","author":"Duszka K.","year":"2022","journal-title":"Cells"},{"key":"e_1_2_12_41_1","doi-asserted-by":"crossref","DOI":"10.3389\/fendo.2023.1017886","article-title":"The role of taurine in male reproduction: physiology, pathology and toxicology","volume":"14","author":"Li Y.","year":"2023","journal-title":"Front. Endocrinol."},{"key":"e_1_2_12_42_1","doi-asserted-by":"crossref","DOI":"10.1038\/nrdp.2017.105","article-title":"Cancer\u2010associated cachexia","volume":"4","author":"Baracos V.E.","year":"2018","journal-title":"Nat. Rev. Dis. Primers."},{"key":"e_1_2_12_43_1","article-title":"Branched\u2010chain amino acid metabolic reprogramming and cancer: molecular mechanisms, immune regulation, and precision targeting","volume":"34","author":"Cai D.","year":"2025","journal-title":"Oncol. Res."},{"key":"e_1_2_12_44_1","doi-asserted-by":"crossref","first-page":"225","DOI":"10.4062\/biomolther.2017.251","article-title":"Effects and mechanisms of taurine as a therapeutic agent","volume":"26","author":"Schaffer S.","year":"2018","journal-title":"Biomol Ther (Seoul)."},{"key":"e_1_2_12_45_1","doi-asserted-by":"crossref","DOI":"10.3892\/mmr.2021.12242","article-title":"Protective role of taurine against oxidative stress (review)","volume":"24","author":"Baliou S.","year":"2021","journal-title":"Mol. Med. Rep."},{"key":"e_1_2_12_46_1","doi-asserted-by":"crossref","first-page":"1705","DOI":"10.21037\/tcr-22-1297","article-title":"Effect of taurine on the proliferation, apoptosis and MST1\/hippo signaling in prostate cancer cells","volume":"11","author":"Song X.","year":"2022","journal-title":"Transl. Cancer Res."},{"issue":"2","key":"e_1_2_12_47_1","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1007\/978-94-024-1079-2_96","article-title":"Taurine attenuates epithelial\u2010mesenchymal transition\u2010related genes in human prostate cancer cells","volume":"975","author":"Tang Y.","year":"2017","journal-title":"Adv. Exp. Med. Biol."},{"key":"e_1_2_12_48_1","doi-asserted-by":"crossref","DOI":"10.3389\/fcell.2021.631163","article-title":"Taurine attenuates the Hypotaurine\u2010induced progression of CRC via ERK\/RSK signaling","volume":"9","author":"Hou X.","year":"2021","journal-title":"Front. Cell Dev. Biol."}],"container-title":["Clinical Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.70442","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cpt.70442","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.70442","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T12:37:28Z","timestamp":1786970248000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/cpt.70442"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,17]]},"references-count":48,"alternative-id":["10.1002\/cpt.70442"],"URL":"https:\/\/doi.org\/10.1002\/cpt.70442","archive":["Portico"],"relation":{},"ISSN":["0009-9236","1532-6535"],"issn-type":[{"value":"0009-9236","type":"print"},{"value":"1532-6535","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,17]]},"assertion":[{"value":"2026-03-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"cpt.70442"}}