{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T13:51:11Z","timestamp":1776174671006,"version":"3.50.1"},"reference-count":52,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T00:00:00Z","timestamp":1772496000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T00:00:00Z","timestamp":1772496000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100000771","name":"Prostate Cancer UK","doi-asserted-by":"publisher","award":["RIA15-ST2-016"],"award-info":[{"award-number":["RIA15-ST2-016"]}],"id":[{"id":"10.13039\/501100000771","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000771","name":"Prostate Cancer UK","doi-asserted-by":"publisher","award":["RIA15-ST2-016"],"award-info":[{"award-number":["RIA15-ST2-016"]}],"id":[{"id":"10.13039\/501100000771","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Wallscourt Foundation"},{"DOI":"10.13039\/100009828","name":"Cancer Research Wales","doi-asserted-by":"publisher","award":["2450"],"award-info":[{"award-number":["2450"]}],"id":[{"id":"10.13039\/100009828","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009828","name":"Cancer Research Wales","doi-asserted-by":"publisher","award":["2494"],"award-info":[{"award-number":["2494"]}],"id":[{"id":"10.13039\/100009828","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Br J Cancer"],"published-print":{"date-parts":[[2026,5,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Prostate cancer is a leading cause of cancer-associated death in men worldwide. Inhibition of the Cellular FLICE-like Inhibitory Protein (cFLIP), which is overexpressed in prostate cancer, alongside TRAIL treatment can trigger apoptosis and suppress cancer stem cell (CSC) activity in different cancer types but has not been fully explored in prostate cancer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Established and primary prostate cancer lines were treated with the cFLIP inhibitor, OH14, in combination with recombinant TRAIL to investigate changes in viability and colony forming potential. Patient-derived xenograft (PDX) tumour cells were treated ex vivo and re-transplanted into mice in limiting dilution assays. Docetaxel resistant PC-3 cells were also treated with OH14 +\/- docetaxel, while PDX tumours were treated in vivo with this combination.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Combined OH14 and TRAIL treatment induced a potent apoptotic response in prostate cancer cells, significantly reducing viability and CSC activity compared to single agents. OH14 also sensitised tumour cells to docetaxel both in vitro and in vivo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Inhibition of cFLIP in combination with either TRAIL or docetaxel has the potential to be used as a novel therapeutic approach to provide more potent, long-lasting benefits to men with prostate cancer.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1038\/s41416-026-03359-4","type":"journal-article","created":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T05:49:35Z","timestamp":1772516975000},"page":"1300-1310","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Inhibition of c-FLIP alongside TRAIL treatment suppresses prostate cancer stem cell activity"],"prefix":"10.1038","volume":"134","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2540-7363","authenticated-orcid":false,"given":"Daniel J.","family":"Turnham","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rhiannon","family":"French","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fiona M.","family":"Frame","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valerie S.","family":"Meniel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norman J.","family":"Maitland","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard W. E.","family":"Clarkson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,3,3]]},"reference":[{"key":"3359_CR1","first-page":"209","volume":"71","author":"H Sung","year":"2021","unstructured":"Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer J Clin. 2021;71:209\u201349.","journal-title":"CA: A Cancer J Clin"},{"key":"3359_CR2","doi-asserted-by":"publisher","first-page":"63","DOI":"10.14740\/wjon1191","volume":"10","author":"P Rawla","year":"2019","unstructured":"Rawla P. Epidemiology of prostate cancer. World J Oncol. 2019;10:63\u201389.","journal-title":"World J Oncol"},{"key":"3359_CR3","doi-asserted-by":"publisher","first-page":"e2119568","DOI":"10.1001\/jamanetworkopen.2021.19568","volume":"4","author":"AO Elmehrath","year":"2021","unstructured":"Elmehrath AO, Afifi AM, Al-Husseini MJ, Saad AM, Wilson N, Shohdy KS, et al. Causes of death among patients with metastatic prostate cancer in the US From 2000 to 2016. JAMA Netw Open. 2021;4:e2119568\u2013e.","journal-title":"JAMA Netw Open"},{"key":"3359_CR4","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1016\/j.eururo.2016.08.002","volume":"71","author":"P Cornford","year":"2017","unstructured":"Cornford P, Bellmunt J, Bolla M, Briers E, De Santis M, Gross T, et al. EAU-ESTRO-SIOG Guidelines on Prostate Cancer. Part II: Treatment of Relapsing, Metastatic, and Castration-Resistant Prostate Cancer. Eur Urol. 2017;71:630\u201342.","journal-title":"Eur Urol"},{"key":"3359_CR5","doi-asserted-by":"crossref","unstructured":"Nagireddy S, Qureshi R, Best J, Frech FS, Shah K, Soni Y, et al. Current Treatment Modalities Targeting Tumor Microenvironment in Castration-Resistant Prostate Cancer. In: Birbrair A, editor. Tumor Microenvironment: Novel Concepts. Cham: Springer International Publishing; 2021. p. 295-323.","DOI":"10.1007\/978-3-030-73119-9_16"},{"key":"3359_CR6","doi-asserted-by":"publisher","first-page":"3822","DOI":"10.1158\/1078-0432.CCR-11-3277","volume":"18","author":"C McCourt","year":"2012","unstructured":"McCourt C, Maxwell P, Mazzucchelli R, Montironi R, Scarpelli M, Salto-Tellez M, et al. Elevation of c-FLIP in Castrate-Resistant Prostate Cancer Antagonizes Therapeutic Response to Androgen Receptor\u2013Targeted Therapy. Clin Cancer Res. 2012;18:3822.","journal-title":"Clin Cancer Res"},{"key":"3359_CR7","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1080\/01926230701320337","volume":"35","author":"S Elmore","year":"2007","unstructured":"Elmore S. Apoptosis: a review of programmed cell death. Toxicol Pathol. 2007;35:495\u2013516.","journal-title":"Toxicol Pathol"},{"key":"3359_CR8","doi-asserted-by":"publisher","first-page":"782","DOI":"10.1038\/nrc2465","volume":"8","author":"RW Johnstone","year":"2008","unstructured":"Johnstone RW, Frew AJ, Smyth MJ. The TRAIL apoptotic pathway in cancer onset, progression and therapy. Nat Rev Cancer. 2008;8:782\u201398.","journal-title":"Nat Rev Cancer"},{"key":"3359_CR9","doi-asserted-by":"publisher","first-page":"1756","DOI":"10.1038\/s41388-019-1100-3","volume":"39","author":"LK Hillert","year":"2020","unstructured":"Hillert LK, Ivanisenko NV, Espe J, K\u00f6nig C, Ivanisenko VA, K\u00e4hne T, et al. Long and short isoforms of c-FLIP act as control checkpoints of DED filament assembly. Oncogene. 2020;39:1756\u201372.","journal-title":"Oncogene"},{"key":"3359_CR10","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1016\/j.trecan.2021.12.002","volume":"8","author":"NV Ivanisenko","year":"2022","unstructured":"Ivanisenko NV, Seyrek K, Hillert-Richter LK, K\u00f6nig C, Espe J, Bose K, et al. Regulation of extrinsic apoptotic signaling by c-FLIP: towards targeting cancer networks. Trends Cancer. 2022;8:190\u2013209.","journal-title":"Trends Cancer"},{"key":"3359_CR11","doi-asserted-by":"publisher","first-page":"1723","DOI":"10.1111\/bph.12238","volume":"169","author":"O Micheau","year":"2013","unstructured":"Micheau O, Shirley S, Dufour F. Death receptors as targets in cancer. Br J Pharm. 2013;169:1723\u201344.","journal-title":"Br J Pharm"},{"key":"3359_CR12","doi-asserted-by":"crossref","unstructured":"Snajdauf M, Havlova K, Vachtenheim J, Ozaniak A, Lischke R, Bartunkova J, et al. The TRAIL in the Treatment of Human Cancer: An Update on Clinical Trials. Frontiers in Molecular Biosciences.8.(2021)","DOI":"10.3389\/fmolb.2021.628332"},{"key":"3359_CR13","doi-asserted-by":"publisher","first-page":"7086","DOI":"10.1158\/0008-5472.CAN-04-1498","volume":"64","author":"X Zhang","year":"2004","unstructured":"Zhang X, Jin T-G, Yang H, DeWolf WC, Khosravi-Far R, Olumi AF. Persistent c-FLIP(L) Expression Is Necessary and Sufficient to Maintain Resistance to Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand\u2013Mediated Apoptosis in Prostate Cancer. Cancer Res. 2004;64:7086\u201391.","journal-title":"Cancer Res"},{"key":"3359_CR14","doi-asserted-by":"publisher","first-page":"2649","DOI":"10.1158\/1535-7163.MCT-08-0148","volume":"7","author":"C Wilson","year":"2008","unstructured":"Wilson C, Wilson T, Johnston PG, Longley DB, Waugh DJJ. Interleukin-8 signaling attenuates TRAIL- and chemotherapy-induced apoptosis through transcriptional regulation of c-FLIP in prostate cancer cells. Mol Cancer Therapeutics. 2008;7:2649.","journal-title":"Mol Cancer Therapeutics"},{"key":"3359_CR15","first-page":"280","volume":"46","author":"UM Nazim","year":"2020","unstructured":"Nazim UM, Yin H, Park SY. Downregulation of c\u2011FLIP and upregulation of DR\u20115 by cantharidin sensitizes TRAIL\u2011mediated apoptosis in prostate cancer cells via autophagy flux. Int J Mol Med. 2020;46:280\u20138.","journal-title":"Int J Mol Med"},{"key":"3359_CR16","doi-asserted-by":"publisher","first-page":"1618","DOI":"10.4161\/cbt.5.12.3352","volume":"5","author":"SJ White","year":"2006","unstructured":"White SJ, Ping L, Keller G, Voelkel-Johnson C. Targeting the short form of cFLIP by RNA interference is sufficient to enhance TRAIL sensitivity in PC3 prostate carcinoma cells. Cancer Biol Ther. 2006;5:1618\u201323.","journal-title":"Cancer Biol Ther"},{"key":"3359_CR17","doi-asserted-by":"publisher","DOI":"10.1186\/bcr2945","volume":"13","author":"L Piggott","year":"2011","unstructured":"Piggott L, Omidvar N, P\u00e9rez SM, Eberl M, Clarkson RWE. Suppression of apoptosis inhibitor c-FLIP selectively eliminates breast cancer stem cell activity in response to the anti-cancer agent, TRAIL. Breast Cancer Res. 2011;13:R88.","journal-title":"Breast Cancer Res"},{"key":"3359_CR18","doi-asserted-by":"publisher","first-page":"S20","DOI":"10.1097\/MD.0000000000004766","volume":"95","author":"JC Chang","year":"2016","unstructured":"Chang JC. Cancer stem cells: Role in tumor growth, recurrence, metastasis, and treatment resistance. Med (Baltim). 2016;95:S20\u2013s5.","journal-title":"Med (Baltim)"},{"key":"3359_CR19","doi-asserted-by":"crossref","unstructured":"Giancotti GFR, Hayward O, lee KY, Robinson T, Ribeiro da Silva A, et al. The discovery of small-molecule inhibitors of cFLIP that sensitise tumour cells to TNF-related apoptosis-inducing ligand. Academia Oncology.2.(2025)","DOI":"10.20935\/AcadOnco7680"},{"key":"3359_CR20","doi-asserted-by":"publisher","first-page":"2117","DOI":"10.1038\/s41418-020-0489-0","volume":"27","author":"LK Hillert","year":"2020","unstructured":"Hillert LK, Ivanisenko NV, Busse D, Espe J, K\u00f6nig C, Peltek SE, et al. Dissecting DISC regulation via pharmacological targeting of caspase-8\/c-FLIPL heterodimer. Cell Death Differ. 2020;27:2117\u201330.","journal-title":"Cell Death Differ"},{"key":"3359_CR21","doi-asserted-by":"publisher","first-page":"710","DOI":"10.3390\/cimb46010046","volume":"46","author":"K Yaacoub","year":"2024","unstructured":"Yaacoub K, Pedeux R, Lafite P, Jarry U, Aci-S\u00e8che S, Bonnet P, et al. The identification of new c-FLIP inhibitors for restoring apoptosis in TRAIL-Resistant Cancer Cells. Curr Issues Mol Biol. 2024;46:710\u201328.","journal-title":"Curr Issues Mol Biol"},{"key":"3359_CR22","doi-asserted-by":"publisher","DOI":"10.1186\/1476-4598-10-126","volume":"10","author":"AJ O\u2019Neill","year":"2011","unstructured":"O\u2019Neill AJ, Prencipe M, Dowling C, Fan Y, Mulrane L, Gallagher WM, et al. Characterisation and manipulation of docetaxel resistant prostate cancer cell lines. Mol Cancer. 2011;10:126.","journal-title":"Mol Cancer"},{"key":"3359_CR23","doi-asserted-by":"crossref","unstructured":"Parry-Jones A, Spary LK The Wales Cancer Bank (WCB). Open Journal of Bioresources.(2018)","DOI":"10.5334\/ojb.46"},{"key":"3359_CR24","doi-asserted-by":"crossref","unstructured":"Frame FM, Pellacani D, Collins AT, Maitland NJ Harvesting Human Prostate Tissue Material and Culturing Primary Prostate Epithelial Cells. In: McEwan PIJ, editor. The Nuclear Receptor Superfamily: Methods and Protocols. New York, NY: Springer New York; 2016. p. 181-201.","DOI":"10.1007\/978-1-4939-3724-0_12"},{"key":"3359_CR25","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1038\/nmeth.2089","volume":"9","author":"CA Schneider","year":"2012","unstructured":"Schneider CA, Rasband WS, Eliceiri KW. NIH Image to ImageJ: 25 years of image analysis. Nat Methods. 2012;9:671\u20135.","journal-title":"Nat Methods"},{"key":"3359_CR26","doi-asserted-by":"publisher","first-page":"e0188228","DOI":"10.1371\/journal.pone.0188228","volume":"12","author":"AJ Taurozzi","year":"2017","unstructured":"Taurozzi AJ, Beekharry R, Wantoch M, Labarthe MC, Walker HF, Seed RI, et al. Spontaneous development of Epstein-Barr Virus associated human lymphomas in a prostate cancer xenograft program. PLoS One. 2017;12:e0188228.","journal-title":"PLoS One"},{"key":"3359_CR27","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-26840-5","volume":"12","author":"M Bolis","year":"2021","unstructured":"Bolis M, Bossi D, Vallerga A, Ceserani V, Cavalli M, Impellizzieri D, et al. Dynamic prostate cancer transcriptome analysis delineates the trajectory to disease progression. Nat Commun. 2021;12:7033.","journal-title":"Nat Commun"},{"key":"3359_CR28","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.neo.2022.01.001","volume":"25","author":"DS Chandrashekar","year":"2022","unstructured":"Chandrashekar DS, Karthikeyan SK, Korla PK, Patel H, Shovon AR, Athar M, et al. UALCAN: An update to the integrated cancer data analysis platform. Neoplasia. 2022;25:18\u201327.","journal-title":"Neoplasia"},{"key":"3359_CR29","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1016\/j.neo.2017.05.002","volume":"19","author":"DS Chandrashekar","year":"2017","unstructured":"Chandrashekar DS, Bashel B, Balasubramanya SAH, Creighton CJ, Ponce-Rodriguez I, Chakravarthi B, et al. UALCAN: A Portal for Facilitating Tumor Subgroup Gene Expression and Survival Analyses. Neoplasia. 2017;19:649\u201358.","journal-title":"Neoplasia"},{"key":"3359_CR30","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.jim.2009.06.008","volume":"347","author":"Y Hu","year":"2009","unstructured":"Hu Y, Smyth GK. ELDA: extreme limiting dilution analysis for comparing depleted and enriched populations in stem cell and other assays. J Immunol Methods. 2009;347:70\u20138.","journal-title":"J Immunol Methods"},{"key":"3359_CR31","doi-asserted-by":"crossref","unstructured":"den Hollander P, Joseph R, Vasaikar S, Kuburich NA, Deshmukh AP, Mani SA Limiting Dilution Tumor Initiation Assay: An In Vivo Approach for the Study of Cancer Stem Cells. In: Kannan N, Beer P, editors. Stem Cell Assays: Methods and Protocols. New York, NY: Springer US; 2022. p. 547-54.","DOI":"10.1007\/978-1-0716-1979-7_38"},{"key":"3359_CR32","doi-asserted-by":"publisher","first-page":"1513","DOI":"10.1056\/NEJMoa041318","volume":"351","author":"DP Petrylak","year":"2004","unstructured":"Petrylak DP, Tangen CM, Hussain MHA, Lara PN, Jones JA, Taplin ME, et al. Docetaxel and Estramustine Compared with Mitoxantrone and Prednisone for Advanced Refractory Prostate Cancer. N Engl J Med. 2004;351:1513\u201320.","journal-title":"N Engl J Med"},{"key":"3359_CR33","doi-asserted-by":"publisher","first-page":"1502","DOI":"10.1056\/NEJMoa040720","volume":"351","author":"IF Tannock","year":"2004","unstructured":"Tannock IF, Wit RD, Berry WR, Horti J, Pluzanska A, Chi KN, et al. Docetaxel plus Prednisone or Mitoxantrone plus Prednisone for Advanced Prostate Cancer. N Engl J Med. 2004;351:1502\u201312.","journal-title":"N Engl J Med"},{"key":"3359_CR34","doi-asserted-by":"publisher","first-page":"e0246733","DOI":"10.1371\/journal.pone.0246733","volume":"16","author":"KA Grayson","year":"2021","unstructured":"Grayson KA, Jyotsana N, Ortiz-Otero N, King MR. Overcoming TRAIL-resistance by sensitizing prostate cancer 3D spheroids with taxanes. PLoS One. 2021;16:e0246733.","journal-title":"PLoS One"},{"key":"3359_CR35","doi-asserted-by":"publisher","first-page":"649","DOI":"10.5534\/wjmh.220073","volume":"41","author":"WH Lee","year":"2023","unstructured":"Lee WH, Kim SC, Kim SH, Yoon JH, Moon KH, Cheon SH, et al. Docetaxel enhances tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in prostate cancer cells via epigenetic gene regulation by enhancer of zeste homolog 2. World J Mens Health. 2023;41:649\u201358.","journal-title":"World J Mens Health"},{"key":"3359_CR36","doi-asserted-by":"publisher","first-page":"833","DOI":"10.1158\/1535-7163.MCT-20-0495","volume":"20","author":"KA Grayson","year":"2021","unstructured":"Grayson KA, Hope JM, Wang W, Reinhart-King CA, King MR. Taxanes sensitize prostate cancer cells to TRAIL-induced apoptotic synergy via endoplasmic reticulum stress. Mol Cancer Ther. 2021;20:833\u201345.","journal-title":"Mol Cancer Ther"},{"key":"3359_CR37","doi-asserted-by":"publisher","first-page":"B129","DOI":"10.1158\/1535-7163.TARG-17-B129","volume":"17","author":"CA Higgins","year":"2018","unstructured":"Higgins CA, Majkut J, Fox J, Humphreys L, Fiedler GE, Boffey RJ, et al. Abstract B129: Development and preclinical assessment of a first-in-class small-molecule inhibitor of FLIP. Mol Cancer Therapeutics. 2018;17:B129\u2013B.","journal-title":"Mol Cancer Therapeutics"},{"key":"3359_CR38","doi-asserted-by":"crossref","unstructured":"Logan IR, McClurg UL, Jones DL, O\u2019Neill DJ, Shaheen FS, Lunec J, et al. Nutlin-3 inhibits androgen receptor-driven c-FLIP expression, resulting in apoptosis of prostate cancer cells. Oncotarget.7.(2016)","DOI":"10.18632\/oncotarget.12542"},{"key":"3359_CR39","doi-asserted-by":"crossref","unstructured":"Zhang X, Wen X, Peng R, Pan Q, Weng D, Ma Y, et al. A first-in-human phase I study of a novel MDM2\/p53 inhibitor alrizomadlin in advanced solid tumors. ESMO Open.9.(2024)","DOI":"10.1016\/j.esmoop.2024.103636"},{"key":"3359_CR40","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1093\/annonc\/mdp270","volume":"21","author":"LR Molife","year":"2010","unstructured":"Molife LR, Attard G, Fong PC, Karavasilis V, Reid AHM, Patterson S, et al. Phase II, two-stage, single-arm trial of the histone deacetylase inhibitor (HDACi) romidepsin in metastatic castration-resistant prostate cancer (CRPC). Ann Oncol. 2010;21:109\u201313.","journal-title":"Ann Oncol"},{"key":"3359_CR41","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1007\/s10637-017-0536-y","volume":"36","author":"X Ouyang","year":"2018","unstructured":"Ouyang X, Shi M, Jie F, Bai Y, Shen P, Yu Z, et al. Phase III study of dulanermin (recombinant human tumor necrosis factor-related apoptosis-inducing ligand\/Apo2 ligand) combined with vinorelbine and cisplatin in patients with advanced non-small-cell lung cancer. Invest N Drugs. 2018;36:315\u201322.","journal-title":"Invest N Drugs"},{"key":"3359_CR42","doi-asserted-by":"publisher","first-page":"8809","DOI":"10.1128\/MCB.25.20.8809-8823.2005","volume":"25","author":"A Panner","year":"2005","unstructured":"Panner A, James CD, Berger MS, Pieper RO. mTOR controls FLIPS translation and TRAIL sensitivity in glioblastoma multiforme cells. Mol Cell Biol. 2005;25:8809\u201323.","journal-title":"Mol Cell Biol"},{"key":"3359_CR43","doi-asserted-by":"publisher","first-page":"7345","DOI":"10.1128\/MCB.00126-06","volume":"26","author":"A Panner","year":"2006","unstructured":"Panner A, Nakamura JL, Parsa AT, Rodriguez-Viciana P, Berger MS, Stokoe D, et al. mTOR-independent translational control of the extrinsic cell death pathway by RalA. Mol Cell Biol. 2006;26:7345\u201357.","journal-title":"Mol Cell Biol"},{"key":"3359_CR44","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1038\/cdd.2010.99","volume":"18","author":"M Bleumink","year":"2011","unstructured":"Bleumink M, K\u00f6hler R, Giaisi M, Proksch P, Krammer PH, Li-Weber M. Rocaglamide breaks TRAIL resistance in HTLV-1-associated adult T-cell leukemia\/lymphoma by translational suppression of c-FLIP expression. Cell Death Differ. 2011;18:362\u201370.","journal-title":"Cell Death Differ"},{"key":"3359_CR45","doi-asserted-by":"publisher","first-page":"5046","DOI":"10.1158\/0008-5472.CAN-09-3979","volume":"70","author":"A Panner","year":"2010","unstructured":"Panner A, Crane CA, Weng C, Feletti A, Fang S, Parsa AT, et al. Ubiquitin-specific protease 8 links the PTEN-Akt-AIP4 pathway to the control of FLIPS stability and TRAIL sensitivity in glioblastoma multiforme. Cancer Res. 2010;70:5046\u201353.","journal-title":"Cancer Res"},{"key":"3359_CR46","doi-asserted-by":"publisher","first-page":"7911","DOI":"10.1158\/0008-5472.CAN-09-1287","volume":"69","author":"A Panner","year":"2009","unstructured":"Panner A, Crane CA, Weng C, Feletti A, Parsa AT, Pieper RO. A novel PTEN-dependent link to ubiquitination controls FLIPS stability and TRAIL sensitivity in glioblastoma multiforme. Cancer Res. 2009;69:7911\u20136.","journal-title":"Cancer Res"},{"key":"3359_CR47","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1677\/jme.1.01991","volume":"36","author":"S Gao","year":"2006","unstructured":"Gao S, Wang H, Lee P, Melamed J, Li CX, Zhang F, et al. Androgen receptor and prostate apoptosis response factor-4 target the c-FLIP gene to determine survival and apoptosis in the prostate gland. J Mol Endocrinol. 2006;36:463\u201383.","journal-title":"J Mol Endocrinol"},{"key":"3359_CR48","doi-asserted-by":"publisher","first-page":"1696","DOI":"10.1002\/pros.20844","volume":"68","author":"KA Raclaw","year":"2008","unstructured":"Raclaw KA, Heemers HV, Kidd EM, Dehm SM, Tindall DJ. Induction of FLIP expression by androgens protects prostate cancer cells from TRAIL-mediated apoptosis. Prostate. 2008;68:1696\u2013706.","journal-title":"Prostate"},{"key":"3359_CR49","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2021.666300","volume":"12","author":"S Ge","year":"2021","unstructured":"Ge S, Hua X, Chen J, Xiao H, Zhang L, Zhou J, et al. Identification of a costimulatory molecule-related signature for predicting prognostic risk in prostate cancer. Front Genet. 2021;12:666300.","journal-title":"Front Genet"},{"key":"3359_CR50","doi-asserted-by":"publisher","first-page":"17861","DOI":"10.1074\/jbc.M116.718536","volume":"291","author":"A Misawa","year":"2016","unstructured":"Misawa A, Takayama K-i, Urano T, Inoue S. Androgen-induced Long Noncoding RNA (lncRNA) SOCS2-AS1 Promotes Cell Growth and Inhibits Apoptosis in Prostate Cancer Cells*. J Biol Chem. 2016;291:17861\u201380.","journal-title":"J Biol Chem"},{"key":"3359_CR51","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1016\/j.eururo.2003.11.032","volume":"45","author":"D Hirano","year":"2004","unstructured":"Hirano D, Okada Y, Minei S, Takimoto Y, Nemoto N. Neuroendocrine differentiation in hormone refractory prostate cancer following androgen deprivation therapy. Eur Urol. 2004;45:586\u201392. discussion 92.","journal-title":"Eur Urol"},{"key":"3359_CR52","doi-asserted-by":"publisher","first-page":"T67","DOI":"10.1530\/ERC-21-0140","volume":"28","author":"H Beltran","year":"2021","unstructured":"Beltran H, Demichelis F. Therapy considerations in neuroendocrine prostate cancer: what next? Endocr Relat Cancer. 2021;28:T67\u2013t78.","journal-title":"Endocr Relat Cancer"}],"container-title":["British Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41416-026-03359-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41416-026-03359-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41416-026-03359-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T13:02:27Z","timestamp":1776171747000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41416-026-03359-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,3]]},"references-count":52,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,5,5]]}},"alternative-id":["3359"],"URL":"https:\/\/doi.org\/10.1038\/s41416-026-03359-4","relation":{},"ISSN":["0007-0920","1532-1827"],"issn-type":[{"value":"0007-0920","type":"print"},{"value":"1532-1827","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,3]]},"assertion":[{"value":"4 June 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 January 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 February 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 March 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The use of human samples was performed in accordance with the Declaration of Helsinki. Patient samples were collected with ethical permission from Castle Hill Hospital (Ethics Number: 07\/H1304\/121) and the Wales Cancer Biobank (Project Number: 16007). Use of patient tissue was approved by the Local Research Ethics Committees. Patients gave informed consent and all patient samples were anonymized. Animal work was approved by the Cardiff University, School of Biosciences ethics committee and performed under UK Home Office licence PP1361991 following ARRIVE 2.0 and NC3R guidelines","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}}]}}