{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T14:21:33Z","timestamp":1776522093408,"version":"3.51.2"},"reference-count":46,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T00:00:00Z","timestamp":1753142400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T00:00:00Z","timestamp":1753142400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"ARTBIO, Norway"},{"name":"The European Union\u2019s Horizon 2020 research and innovation programme","award":["No 101008571 (PRISMAP)"],"award-info":[{"award-number":["No 101008571 (PRISMAP)"]}]},{"DOI":"10.13039\/100008730","name":"Kreftforeningen","doi-asserted-by":"publisher","award":["273672 & 198016"],"award-info":[{"award-number":["273672 & 198016"]}],"id":[{"id":"10.13039\/100008730","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002341","name":"Research Council of Finland","doi-asserted-by":"publisher","award":["349314"],"award-info":[{"award-number":["349314"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Radforsk, Oslo, Norway","award":["TARACAN"],"award-info":[{"award-number":["TARACAN"]}]},{"DOI":"10.13039\/501100005366","name":"University of Oslo","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005366","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Med Oncol"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>The alpha-emitting radioligand [<jats:sup>212<\/jats:sup>Pb]Pb-AB001, targeting prostate-specific membrane antigen (PSMA), is a promising therapy approach for prostate cancer. Bromodomain and extra-terminal (BET) protein inhibitors, such as AZD5153 and JQ1, disrupt oncogenic transcriptional programs by altering chromatin structure. This study evaluated whether BET inhibition enhances the efficacy of radioligand therapy. Cytotoxic effects of [<jats:sup>212<\/jats:sup>Pb]Pb-AB001 alone and in combination with BET inhibitors were assessed in 2D monolayers and a 3D spheroid model of PSMA-positive C4-2 prostate cancer cells. Cell viability, cell cycle alterations, and DNA damage were assessed using viability assays and flow cytometry. Spheroid growth and viability were assessed by fluorescence microscopy. AZD5153 was more potent than JQ1 in reducing cell proliferation. [<jats:sup>212<\/jats:sup>Pb]Pb-AB001 induced activity- and time-dependent cytotoxicity with a delayed apoptotic response. BET inhibitors induced G1 arrest, while [<jats:sup>212<\/jats:sup>Pb]Pb-AB001 caused G2 arrest. Combination treatment reduced cell viability in an additive manner but did not further affect cell cycle distribution or increase apoptosis compared with [<jats:sup>212<\/jats:sup>Pb]Pb-AB001 alone. \u03b3H2AX staining in 2D models showed an activity- and time-dependent increase in DNA damage at 1, 3 and 6\u00a0days post-treatment with [<jats:sup>212<\/jats:sup>Pb]Pb-AB001. BET inhibitors alone induced minimal \u03b3H2AX, and combination treatments did not enhance DNA damage beyond [<jats:sup>212<\/jats:sup>Pb]Pb-AB001 alone. In 3D spheroids, combination treatment led to synergistic growth suppression. In conclusion, these findings indicate that therapeutic inhibition of BET bromodomain in combination with the alpha-emitting radioligand [<jats:sup>212<\/jats:sup>Pb]Pb-AB001 could significantly enhance tumour control and should be further evaluated in metastatic prostate cancer models.<\/jats:p>","DOI":"10.1007\/s12032-025-02925-9","type":"journal-article","created":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T06:23:52Z","timestamp":1753165432000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Combination of PSMA targeting alpha-emitting radioligand [212Pb]Pb-AB001 with BET bromodomain inhibitors in in vitro prostate cancer models"],"prefix":"10.1007","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-7547-3287","authenticated-orcid":false,"given":"Rugile","family":"Liukaityte","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4329-5411","authenticated-orcid":false,"given":"Vilde Yuli","family":"Stenberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6679-6705","authenticated-orcid":false,"given":"Andrius","family":"Kleinauskas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0114-903X","authenticated-orcid":false,"given":"Petras","family":"Juzenas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2931-3652","authenticated-orcid":false,"given":"Alfonso","family":"Urbanucci","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9426-0062","authenticated-orcid":false,"given":"Asta","family":"Juzeniene","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,7,22]]},"reference":[{"key":"2925_CR1","doi-asserted-by":"publisher","first-page":"1336","DOI":"10.1002\/ijc.35278","volume":"156","author":"AM Filho","year":"2024","unstructured":"Filho AM, et al. The GLOBOCAN 2022 cancer estimates: data sources, methods, and a snapshot of the cancer burden worldwide. Int J Cancer. 2024;156:1336.","journal-title":"Int J Cancer"},{"issue":"7","key":"2925_CR2","doi-asserted-by":"publisher","first-page":"914","DOI":"10.1007\/s11864-024-01215-2","volume":"25","author":"T Kulasegaran","year":"2024","unstructured":"Kulasegaran T, et al. Metastatic castration-resistant prostate cancer: advances in treatment and symptom management. Curr Treat Options Oncol. 2024;25(7):914\u201331.","journal-title":"Curr Treat Options Oncol"},{"issue":"4","key":"2925_CR3","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1016\/j.eururo.2019.06.030","volume":"76","author":"A Paschalis","year":"2019","unstructured":"Paschalis A, et al. Prostate-specific membrane antigen heterogeneity and DNA repair defects in prostate cancer. Eur Urol. 2019;76(4):469\u201378.","journal-title":"Eur Urol"},{"issue":"12","key":"2925_CR4","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.1056\/NEJMoa2107322","volume":"385","author":"O Sartor","year":"2021","unstructured":"Sartor O, et al. Lutetium-177-PSMA-617 for metastatic castration-resistant prostate cancer. N Engl J Med. 2021;385(12):1091\u2013103.","journal-title":"N Engl J Med"},{"issue":"10459","key":"2925_CR5","doi-asserted-by":"publisher","first-page":"1227","DOI":"10.1016\/S0140-6736(24)01653-2","volume":"404","author":"MJ Morris","year":"2024","unstructured":"Morris MJ, et al. 177Lu-PSMA-617 versus a change of androgen receptor pathway inhibitor therapy for taxane-naive patients with progressive metastatic castration-resistant prostate cancer (PSMAfore): a phase 3, randomised, controlled trial. Lancet. 2024;404(10459):1227\u201339.","journal-title":"Lancet"},{"issue":"1","key":"2925_CR6","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1358\/dot.2023.59.1.3476574","volume":"59","author":"X Liu","year":"2023","unstructured":"Liu X, et al. Lutetium Lu 177 vipivotide tetraxetan for prostate cancer. Drugs Today (Barc). 2023;59(1):37\u201349.","journal-title":"Drugs Today (Barc)"},{"issue":"5","key":"2925_CR7","doi-asserted-by":"publisher","first-page":"795","DOI":"10.2967\/jnumed.117.203539","volume":"59","author":"C Kratochwil","year":"2018","unstructured":"Kratochwil C, et al. Targeted \u03b1-therapy of metastatic castration-resistant prostate cancer with 225Ac-PSMA-617: swimmer-plot analysis suggests efficacy regarding duration of tumor control. J Nucl Med. 2018;59(5):795\u2013802.","journal-title":"J Nucl Med"},{"key":"2925_CR8","doi-asserted-by":"publisher","first-page":"692436","DOI":"10.3389\/fmed.2021.692436","volume":"8","author":"JP Pouget","year":"2021","unstructured":"Pouget JP, et al. Revisiting the radiobiology of targeted alpha therapy. Front Med (Lausanne). 2021;8:692436.","journal-title":"Front Med (Lausanne)"},{"issue":"3","key":"2925_CR9","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1016\/j.cpet.2024.03.006","volume":"19","author":"H Song","year":"2024","unstructured":"Song H, et al. Alpha and beta radiation for theragnostics. PET Clin. 2024;19(3):307\u201323.","journal-title":"PET Clin"},{"issue":"11","key":"2925_CR10","doi-asserted-by":"publisher","first-page":"1363","DOI":"10.1007\/s11912-023-01458-6","volume":"25","author":"D Arbuznikova","year":"2023","unstructured":"Arbuznikova D, et al. Towards improving the efficacy of PSMA-targeting radionuclide therapy for late-stage prostate cancer-combination strategies. Curr Oncol Rep. 2023;25(11):1363\u201374.","journal-title":"Curr Oncol Rep"},{"issue":"Pt A","key":"2925_CR11","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.mce.2017.06.007","volume":"462","author":"A Urbanucci","year":"2018","unstructured":"Urbanucci A, et al. Bromodomain-containing proteins in prostate cancer. Mol Cell Endocrinol. 2018;462(Pt A):31\u201340.","journal-title":"Mol Cell Endocrinol"},{"issue":"10","key":"2925_CR12","doi-asserted-by":"publisher","first-page":"2045","DOI":"10.1016\/j.celrep.2017.05.049","volume":"19","author":"A Urbanucci","year":"2017","unstructured":"Urbanucci A, et al. Androgen receptor deregulation drives bromodomain-mediated chromatin alterations in prostate cancer. Cell Rep. 2017;19(10):2045\u201359.","journal-title":"Cell Rep"},{"issue":"13","key":"2925_CR13","doi-asserted-by":"publisher","first-page":"3149","DOI":"10.1158\/1078-0432.CCR-17-3571","volume":"24","author":"J Welti","year":"2018","unstructured":"Welti J, et al. Targeting bromodomain and extra-terminal (BET) family proteins in castration-resistant prostate cancer (CRPC). Clin Cancer Res. 2018;24(13):3149\u201362.","journal-title":"Clin Cancer Res"},{"issue":"7504","key":"2925_CR14","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1038\/nature13229","volume":"510","author":"IA Asangani","year":"2014","unstructured":"Asangani IA, et al. Therapeutic targeting of BET bromodomain proteins in castration-resistant prostate cancer. Nature. 2014;510(7504):278\u201382.","journal-title":"Nature"},{"issue":"3","key":"2925_CR15","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1016\/j.celrep.2017.12.078","volume":"22","author":"X Li","year":"2018","unstructured":"Li X, et al. BRD4 promotes DNA repair and mediates the formation of TMPRSS2-ERG gene rearrangements in prostate cancer. Cell Rep. 2018;22(3):796\u2013808.","journal-title":"Cell Rep"},{"issue":"3","key":"2925_CR16","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1080\/13543784.2023.2186851","volume":"32","author":"A Mandl","year":"2023","unstructured":"Mandl A, et al. Role of bromodomain and extraterminal (BET) proteins in prostate cancer. Expert Opin Investig Drugs. 2023;32(3):213\u201328.","journal-title":"Expert Opin Investig Drugs"},{"issue":"9","key":"2925_CR17","doi-asserted-by":"publisher","first-page":"e152955","DOI":"10.1172\/jci.insight.152955","volume":"7","author":"X Li","year":"2022","unstructured":"Li X, et al. Targeting radioresistance and replication fork stability in prostate cancer. JCI Insight. 2022;7(9):e152955.","journal-title":"JCI Insight"},{"issue":"4","key":"2925_CR18","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1158\/1541-7786.MCR-15-0472","volume":"14","author":"IA Asangani","year":"2016","unstructured":"Asangani IA, et al. bet bromodomain inhibitors enhance efficacy and disrupt resistance to AR antagonists in the treatment of prostate cancer. Mol Cancer Res. 2016;14(4):324\u201331.","journal-title":"Mol Cancer Res"},{"key":"2925_CR19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/13543776.2025.2548586","volume":"35","author":"Y Chen","year":"2025","unstructured":"Chen Y, et al. A patent review of BRD4 inhibitors (2020-present). Expert Opin Ther Pat. 2025;35:1\u201316.","journal-title":"Expert Opin Ther Pat"},{"issue":"10","key":"2925_CR20","doi-asserted-by":"publisher","first-page":"1154","DOI":"10.1158\/1535-7163.MCT-23-0065","volume":"22","author":"EP Hamilton","year":"2023","unstructured":"Hamilton EP, et al. First-in-human study of AZD5153, a small-molecule inhibitor of bromodomain protein 4, in patients with relapsed\/refractory malignant solid tumors and lymphoma. Mol Cancer Ther. 2023;22(10):1154\u201365.","journal-title":"Mol Cancer Ther"},{"key":"2925_CR21","doi-asserted-by":"publisher","first-page":"732","DOI":"10.2967\/jnumed.124.269299","volume":"66","author":"K Berner","year":"2025","unstructured":"Berner K, et al. First-in-human phase 0 study of AB001, a prostate-specific membrane antigen-targeted 212Pb radioligand, in patients with metastatic castration-resistant prostate cancer. J Nucl Med. 2025;66:732.","journal-title":"J Nucl Med"},{"issue":"2","key":"2925_CR22","doi-asserted-by":"publisher","first-page":"798","DOI":"10.1159\/000494244","volume":"50","author":"G Shen","year":"2018","unstructured":"Shen G, et al. AZD5153 inhibits prostate cancer cell growth in vitro and in vivo. Cell Physiol Biochem. 2018;50(2):798\u2013809.","journal-title":"Cell Physiol Biochem"},{"issue":"1","key":"2925_CR23","doi-asserted-by":"publisher","first-page":"397","DOI":"10.18632\/aging.102630","volume":"12","author":"J Wang","year":"2020","unstructured":"Wang J, et al. The combined effect of epigenetic inhibitors for LSD1 and BRD4 alters prostate cancer growth and invasion. Aging (Albany NY). 2020;12(1):397\u2013415.","journal-title":"Aging (Albany NY)"},{"key":"2925_CR24","doi-asserted-by":"publisher","first-page":"839620","DOI":"10.3389\/fphar.2022.839620","volume":"13","author":"Y Xu","year":"2022","unstructured":"Xu Y, et al. Evaluation of JQ1 combined with docetaxel for the treatment of prostate cancer cells in 2D- and 3D-culture systems. Front Pharmacol. 2022;13:839620.","journal-title":"Front Pharmacol"},{"issue":"7","key":"2925_CR25","doi-asserted-by":"publisher","first-page":"114431","DOI":"10.1016\/j.celrep.2024.114431","volume":"43","author":"Y Zhang","year":"2024","unstructured":"Zhang Y, et al. Elevating PLK1 overcomes BETi resistance in prostate cancer via triggering BRD4 phosphorylation-dependent degradation in mitosis. Cell Rep. 2024;43(7):114431.","journal-title":"Cell Rep"},{"issue":"1","key":"2925_CR26","doi-asserted-by":"publisher","first-page":"173","DOI":"10.2967\/jnumed.122.264009","volume":"64","author":"RG Li","year":"2023","unstructured":"Li RG, et al. An experimental generator for production of high-purity 212Pb for use in radiopharmaceuticals. J Nucl Med. 2023;64(1):173\u20136.","journal-title":"J Nucl Med"},{"issue":"11","key":"2925_CR27","doi-asserted-by":"publisher","first-page":"2784","DOI":"10.3390\/cancers14112784","volume":"14","author":"VY Stenberg","year":"2022","unstructured":"Stenberg VY, et al. Factors influencing the therapeutic efficacy of the PSMA targeting radioligand 212Pb-NG001. Cancers (Basel). 2022;14(11):2784.","journal-title":"Cancers (Basel)"},{"key":"2925_CR28","doi-asserted-by":"publisher","first-page":"109362","DOI":"10.1016\/j.apradiso.2020.109362","volume":"166","author":"E Napoli","year":"2020","unstructured":"Napoli E, et al. Calibration of sodium iodide detectors and reentrant ionization chambers for 212Pb activity in different geometries by HPGe activity determined samples. Appl Radiat Isot. 2020;166:109362.","journal-title":"Appl Radiat Isot"},{"issue":"3","key":"2925_CR29","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1002\/jlcr.3825","volume":"63","author":"VY Stenberg","year":"2020","unstructured":"Stenberg VY, et al. Preparation of the alpha-emitting prostate-specific membrane antigen targeted radioligand [212Pb]Pb-NG001 for prostate cancer. J Labelled Comp Radiopharm. 2020;63(3):129\u201343.","journal-title":"J Labelled Comp Radiopharm"},{"issue":"9","key":"2925_CR30","doi-asserted-by":"publisher","first-page":"4815","DOI":"10.3390\/ijms22094815","volume":"22","author":"VY Stenberg","year":"2021","unstructured":"Stenberg VY, et al. Evaluation of the PSMA-binding ligand 212Pb-NG001 in multicellular tumour spheroid and mouse models of prostate cancer. Int J Mol Sci. 2021;22(9):4815.","journal-title":"Int J Mol Sci"},{"issue":"11","key":"2925_CR31","doi-asserted-by":"publisher","first-page":"e0224137","DOI":"10.1371\/journal.pone.0224137","volume":"14","author":"E Demidenko","year":"2019","unstructured":"Demidenko E, et al. Statistical determination of synergy based on Bliss definition of drugs independence. PLoS ONE. 2019;14(11):e0224137.","journal-title":"PLoS ONE"},{"issue":"2","key":"2925_CR32","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1158\/0008-5472.CAN-09-1947","volume":"70","author":"TC Chou","year":"2010","unstructured":"Chou TC. Drug combination studies and their synergy quantification using the Chou-Talalay method. Cancer Res. 2010;70(2):440\u20136.","journal-title":"Cancer Res"},{"issue":"8","key":"2925_CR33","doi-asserted-by":"publisher","first-page":"985","DOI":"10.1080\/095530099139746","volume":"75","author":"OV Belyakov","year":"1999","unstructured":"Belyakov OV, et al. Delayed lethality, apoptosis and micronucleus formation in human fibroblasts irradiated with x-rays or alpha-particles. Int J Radiat Biol. 1999;75(8):985\u201393.","journal-title":"Int J Radiat Biol"},{"key":"2925_CR34","doi-asserted-by":"publisher","first-page":"e15","DOI":"10.1017\/erm.2022.6","volume":"24","author":"Z Nikitaki","year":"2022","unstructured":"Nikitaki Z, et al. Key biological mechanisms involved in high-LET radiation therapies with a focus on DNA damage and repair. Expert Rev Mol Med. 2022;24:e15.","journal-title":"Expert Rev Mol Med"},{"issue":"4","key":"2925_CR35","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1007\/s002590100484","volume":"28","author":"JP Pouget","year":"2001","unstructured":"Pouget JP, et al. General aspects of the cellular response to low- and high-LET radiation. Eur J Nucl Med. 2001;28(4):541\u201361.","journal-title":"Eur J Nucl Med"},{"issue":"9","key":"2925_CR36","first-page":"491","volume":"73","author":"X Shi","year":"2018","unstructured":"Shi X, et al. JQ1: a novel potential therapeutic target. Pharmazie. 2018;73(9):491\u20133.","journal-title":"Pharmazie"},{"issue":"12","key":"2925_CR37","doi-asserted-by":"publisher","first-page":"1391","DOI":"10.1080\/13543784.2017.1393518","volume":"26","author":"MC Markowski","year":"2017","unstructured":"Markowski MC, et al. BET inhibitors in metastatic prostate cancer: therapeutic implications and rational drug combinations. Expert Opin Investig Drugs. 2017;26(12):1391\u20137.","journal-title":"Expert Opin Investig Drugs"},{"issue":"10","key":"2925_CR38","doi-asserted-by":"publisher","first-page":"2013","DOI":"10.1038\/bjc.2013.189","volume":"108","author":"KJ Yong","year":"2013","unstructured":"Yong KJ, et al. 212Pb-radioimmunotherapy potentiates paclitaxel-induced cell killing efficacy by perturbing the mitotic spindle checkpoint. Br J Cancer. 2013;108(10):2013\u201320.","journal-title":"Br J Cancer"},{"key":"2925_CR39","doi-asserted-by":"publisher","first-page":"877302","DOI":"10.3389\/fonc.2022.877302","volume":"12","author":"FDC Guerra Liberal","year":"2022","unstructured":"Guerra Liberal FDC, et al. Differential responses to 223Ra and alpha-particles exposure in prostate cancer driven by mitotic catastrophe. Front Oncol. 2022;12:877302.","journal-title":"Front Oncol"},{"issue":"3","key":"2925_CR40","doi-asserted-by":"publisher","first-page":"776","DOI":"10.1016\/j.ijrobp.2017.11.012","volume":"100","author":"RJ Carter","year":"2018","unstructured":"Carter RJ, et al. Complex DNA damage induced by high linear energy transfer alpha-particles and protons triggers a specific cellular DNA damage response. Int J Radiat Oncol Biol Phys. 2018;100(3):776\u201384.","journal-title":"Int J Radiat Oncol Biol Phys"},{"issue":"20","key":"2925_CR41","doi-asserted-by":"publisher","first-page":"11102","DOI":"10.3390\/ijms222011102","volume":"22","author":"J Sarnik","year":"2021","unstructured":"Sarnik J, et al. BET proteins as attractive targets for cancer therapeutics. Int J Mol Sci. 2021;22(20):11102.","journal-title":"Int J Mol Sci"},{"issue":"2","key":"2925_CR42","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1007\/s10637-018-0623-8","volume":"37","author":"T Takimoto-Shimomura","year":"2019","unstructured":"Takimoto-Shimomura T, et al. Dual targeting of bromodomain-containing 4 by AZD5153 and BCL2 by AZD4320 against B-cell lymphomas concomitantly overexpressing c-MYC and BCL2. Invest New Drugs. 2019;37(2):210\u201322.","journal-title":"Invest New Drugs"},{"issue":"19","key":"2925_CR43","doi-asserted-by":"publisher","first-page":"4691","DOI":"10.3390\/cancers14194691","volume":"14","author":"S Sender","year":"2022","unstructured":"Sender S, et al. Evaluation of the synergistic potential of simultaneous pan- or isoform-specific BET and SYK inhibition in B-cell lymphoma: an in vitro approach. Cancers (Basel). 2022;14(19):4691.","journal-title":"Cancers (Basel)"},{"issue":"4","key":"2925_CR44","doi-asserted-by":"publisher","first-page":"1114","DOI":"10.1002\/ijc.32515","volume":"146","author":"Y Takashima","year":"2020","unstructured":"Takashima Y, et al. Bromodomain and extraterminal domain inhibition synergizes with WEE1-inhibitor AZD1775 effect by impairing nonhomologous end joining and enhancing DNA damage in nonsmall cell lung cancer. Int J Cancer. 2020;146(4):1114\u201324.","journal-title":"Int J Cancer"},{"issue":"7","key":"2925_CR45","doi-asserted-by":"publisher","first-page":"3043","DOI":"10.3390\/molecules28073043","volume":"28","author":"KKW To","year":"2023","unstructured":"To KKW, et al. BET bromodomain inhibitors: novel design strategies and therapeutic applications. Molecules. 2023;28(7):3043.","journal-title":"Molecules"},{"issue":"20","key":"2925_CR46","doi-asserted-by":"publisher","first-page":"5338","DOI":"10.1158\/1078-0432.CCR-20-1707","volume":"26","author":"RR Aggarwal","year":"2020","unstructured":"Aggarwal RR, et al. A phase Ib\/IIa study of the Pan-BET inhibitor ZEN-3694 in combination with enzalutamide in patients with metastatic castration-resistant prostate cancer. Clin Cancer Res. 2020;26(20):5338\u201347.","journal-title":"Clin Cancer Res"}],"container-title":["Medical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12032-025-02925-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12032-025-02925-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12032-025-02925-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,7]],"date-time":"2025-09-07T18:55:50Z","timestamp":1757271350000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12032-025-02925-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,22]]},"references-count":46,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["2925"],"URL":"https:\/\/doi.org\/10.1007\/s12032-025-02925-9","relation":{},"ISSN":["1559-131X"],"issn-type":[{"value":"1559-131X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,22]]},"assertion":[{"value":"2 April 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 July 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 July 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Not Applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"All authors consent to the publication of this.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}],"article-number":"362"}}