{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T22:22:07Z","timestamp":1790461327725,"version":"4.1.0"},"reference-count":57,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:00:00Z","timestamp":1769731200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T00:00:00Z","timestamp":1771891200000},"content-version":"vor","delay-in-days":25,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"the Outstanding Innovative Research Team for Molecular Enzymology and Detection in Anhui Provincial Universities","award":["2022AH010012"],"award-info":[{"award-number":["2022AH010012"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["22277131"],"award-info":[{"award-number":["22277131"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82171558"],"award-info":[{"award-number":["82171558"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"crossref","award":["2023YFC3603300"],"award-info":[{"award-number":["2023YFC3603300"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Yunnan Fundamental Research Projects","award":["202305AH340006"],"award-info":[{"award-number":["202305AH340006"]}]},{"name":"CAS \"Light of West China\"","award":["xbzg-zdsys-202312"],"award-info":[{"award-number":["xbzg-zdsys-202312"]}]},{"name":"Academician Expert Workstation of Yunnan Kunming","award":["YSZJGZZ-2022063"],"award-info":[{"award-number":["YSZJGZZ-2022063"]}]},{"name":"Technology Talent and Platform Plan of Yunnan Province","award":["202305AF150160"],"award-info":[{"award-number":["202305AF150160"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Med"],"DOI":"10.1186\/s12916-026-04671-9","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T09:34:59Z","timestamp":1769765699000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Targeting BCL-XL for degradation synergizes with gemcitabine against cholangiocarcinoma"],"prefix":"10.1186","volume":"24","author":[{"given":"Qinghua","family":"Zeng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiwen","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongzhang","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuni","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Lai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoping","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonghan","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,30]]},"reference":[{"key":"4671_CR1","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1111\/liv.14101","volume":"39","author":"JM Banales","year":"2019","unstructured":"Banales JM, Cardinale V, Macias RIR, et al. Cholangiocarcinoma: state-of-the-art knowledge and challenges. Liver Int. 2019;39:5\u20136.","journal-title":"Liver Int"},{"issue":"9","key":"4671_CR2","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1038\/s41575-020-0310-z","volume":"17","author":"JM Banales","year":"2020","unstructured":"Banales JM, Marin JJG, Lamarca A, et al. Cholangiocarcinoma 2020: the next horizon in mechanisms and management. Nat Rev Gastroenterol Hepatol. 2020;17(9):557\u201388.","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"4671_CR3","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.jhep.2019.09.007","volume":"72","author":"O Clements","year":"2020","unstructured":"Clements O, Eliahoo J, Kim JU, Taylor-Robinson SD, Khan SA. Risk factors for intrahepatic and extrahepatic cholangiocarcinoma: a systematic review and meta-analysis. J Hepatol. 2020;72:95\u2013103.","journal-title":"J Hepatol"},{"key":"4671_CR4","first-page":"17","volume":"73","author":"RL Siegel","year":"2023","unstructured":"Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023;73:17\u201348.","journal-title":"CA Cancer J Clin"},{"key":"4671_CR5","doi-asserted-by":"publisher","first-page":"2168","DOI":"10.1016\/S0140-6736(13)61903-0","volume":"383","author":"N Razumilava","year":"2014","unstructured":"Razumilava N, Gores GJ. Cholangiocarcinoma. Lancet. 2014;383:2168\u201379.","journal-title":"Lancet"},{"key":"4671_CR6","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1016\/j.suc.2018.12.004","volume":"99","author":"AS Khan","year":"2019","unstructured":"Khan AS, Dageforde LA. Cholangiocarcinoma. Surg Clin North Am. 2019;99:315\u201335.","journal-title":"Surg Clin North Am"},{"key":"4671_CR7","doi-asserted-by":"publisher","first-page":"1451474","DOI":"10.3389\/fimmu.2024.1451474","volume":"15","author":"F Chen","year":"2024","unstructured":"Chen F, Sheng J, Li X, et al. Tumor-associated macrophages: orchestrators of cholangiocarcinoma progression. Front Immunol. 2024;15:1451474.","journal-title":"Front Immunol"},{"key":"4671_CR8","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1038\/nrm3722","volume":"15","author":"PE Czabotar","year":"2014","unstructured":"Czabotar PE, Lessene G, Strasser A, Adams JM. Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy. Nat Rev Mol Cell Biol. 2014;15:49\u201363.","journal-title":"Nat Rev Mol Cell Biol"},{"key":"4671_CR9","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1016\/j.molcel.2010.01.025","volume":"37","author":"JE Chipuk","year":"2010","unstructured":"Chipuk JE, Moldoveanu T, Llambi F, Parsons MJ, Green DR. The BCL-2 family reunion. Mol Cell. 2010;37:299\u2013310.","journal-title":"Mol Cell"},{"key":"4671_CR10","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","volume":"144","author":"D Hanahan","year":"2011","unstructured":"Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646\u201374.","journal-title":"Cell"},{"key":"4671_CR11","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1038\/nrclinonc.2017.157","volume":"15","author":"SI Ilyas","year":"2018","unstructured":"Ilyas SI, Khan SA, Hallemeier CL, Kelley RK, Gores GJ. Cholangiocarcinoma - evolving concepts and therapeutic strategies. Nat Rev Clin Oncol. 2018;15:95\u2013111.","journal-title":"Nat Rev Clin Oncol"},{"key":"4671_CR12","first-page":"546","volume":"9","author":"X Ding","year":"2019","unstructured":"Ding X, Zhang Y, Huang T, et al. Targeting sphingosine kinase 2 suppresses cell growth and synergizes with BCL2\/BCL-XL inhibitors through NOXA-mediated MCL1 degradation in cholangiocarcinoma. Am J Cancer Res. 2019;9:546\u201361.","journal-title":"Am J Cancer Res"},{"issue":"12","key":"4671_CR13","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1038\/nrd2658","volume":"7","author":"G Lessene","year":"2008","unstructured":"Lessene G, Czabotar PE, Colman PM. Bcl-2 family antagonists for cancer therapy. Nat Rev Drug Discov. 2008;7(12):989\u20131000.","journal-title":"Nat Rev Drug Discov"},{"issue":"5","key":"4671_CR14","doi-asserted-by":"publisher","first-page":"943","DOI":"10.1038\/sj.cdd.4402081","volume":"14","author":"H Zhang","year":"2007","unstructured":"Zhang H, Nimmer PM, Tahir SK, et al. Bcl-2 family proteins are essential for platelet survival. Cell Death Differ. 2007;14(5):943\u201351.","journal-title":"Cell Death Differ"},{"issue":"6","key":"4671_CR15","first-page":"1173","volume":"128","author":"KD Mason","year":"2007","unstructured":"Mason KD, Carpinelli MR, Fletcher JI, et al. Programmed anuclear cell death delimits platelet life span. Cell Death Differ. 2007;128(6):1173\u201386.","journal-title":"Cell Death Differ"},{"issue":"11","key":"4671_CR16","doi-asserted-by":"publisher","first-page":"3163","DOI":"10.1158\/1078-0432.CCR-11-3090","volume":"18","author":"CM Rudin","year":"2012","unstructured":"Rudin CM, Hann CL, Garon EB, et al. Phase II study of single-agent navitoclax (ABT-263) and biomarker correlates in patients with relapsed small cell lung cancer. Clin Cancer Res. 2012;18(11):3163\u20139.","journal-title":"Clin Cancer Res"},{"issue":"9","key":"4671_CR17","doi-asserted-by":"publisher","first-page":"3421","DOI":"10.1158\/0008-5472.CAN-07-5836","volume":"68","author":"C Tse","year":"2008","unstructured":"Tse C, Shoemaker AR, Adickes J, et al. ABT-263: a potent and orally bioavailable Bcl-2 family inhibitor. Cancer Res. 2008;68(9):3421\u20138.","journal-title":"Cancer Res"},{"issue":"10","key":"4671_CR18","doi-asserted-by":"publisher","first-page":"638","DOI":"10.1038\/s41568-021-00365-x","volume":"21","author":"B Dale","year":"2021","unstructured":"Dale B, Cheng M, Park KS, Kaniskan H\u00dc, Xiong Y, Jin J. Advancing targeted protein degradation for cancer therapy. Nat Rev Cancer. 2021;21(10):638\u201354.","journal-title":"Nat Rev Cancer"},{"key":"4671_CR19","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1038\/s41589-019-0362-y","volume":"15","author":"PP Chamberlain","year":"2019","unstructured":"Chamberlain PP, Hamann LG. Development of targeted protein degradation therapeutics. Nat Chem Biol. 2019;15:937\u201344.","journal-title":"Nat Chem Biol"},{"key":"4671_CR20","doi-asserted-by":"publisher","first-page":"114112","DOI":"10.1016\/j.biopha.2022.114112","volume":"158","author":"X Jia","year":"2023","unstructured":"Jia X, Han X. Targeting androgen receptor degradation with PROTACs from bench to bedside. Biomed Pharmacother. 2023;158:114112.","journal-title":"Biomed Pharmacother"},{"key":"4671_CR21","doi-asserted-by":"publisher","first-page":"112186","DOI":"10.1016\/j.ejmech.2020.112186","volume":"192","author":"X Zhang","year":"2020","unstructured":"Zhang X, Thummuri D, Liu X, et al. Discovery of PROTAC BCL-X(L) degraders as potent anticancer agents with low on-target platelet toxicity. Eur J Med Chem. 2020;192:112186.","journal-title":"Eur J Med Chem"},{"key":"4671_CR22","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1186\/s13045-020-00928-9","volume":"13","author":"Y He","year":"2020","unstructured":"He Y, Koch R, Budamagunta V, et al. DT2216\u2014a Bcl-xL-specific degrader is highly active against Bcl-xL-dependent T cell lymphomas. J Hematol Oncol. 2020;13:95.","journal-title":"J Hematol Oncol"},{"key":"4671_CR23","doi-asserted-by":"publisher","first-page":"3495","DOI":"10.1039\/D5MD00119F","volume":"16","author":"P Zhang","year":"2025","unstructured":"Zhang P, Thummuri D, Hu W, et al. Discovery of PZ671, a highly potent and in vivo active CRBN-recruiting Bcl-xL degrader. RSC Med Chem. 2025;16:3495\u2013506.","journal-title":"RSC Med Chem"},{"key":"4671_CR24","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1007\/978-1-4939-3578-9_6","volume":"1418","author":"Z Wang","year":"2016","unstructured":"Wang Z, Jensen MA, Zenklusen JC. A practical guide to the cancer genome atlas (TCGA). Methods Mol Biol. 2016;1418:111\u201341.","journal-title":"Methods Mol Biol"},{"key":"4671_CR25","doi-asserted-by":"publisher","first-page":"W556","DOI":"10.1093\/nar\/gkz430","volume":"47","author":"Z Tang","year":"2019","unstructured":"Tang Z, Kang B, Li C, Chen T, Zhang Z. GEPIA2: an enhanced web server for large-scale expression profiling and interactive analysis. Nucleic Acids Res. 2019;47:W556\u201360.","journal-title":"Nucleic Acids Res"},{"key":"4671_CR26","doi-asserted-by":"publisher","first-page":"1938","DOI":"10.1038\/s41591-019-0668-z","volume":"25","author":"S Khan","year":"2019","unstructured":"Khan S, Zhang X, Lv D, et al. A selective BCL-X(L) PROTAC degrader achieves safe and potent antitumor activity. Nat Med. 2019;25:1938\u201347.","journal-title":"Nat Med"},{"key":"4671_CR27","doi-asserted-by":"publisher","first-page":"279ra40","DOI":"10.1126\/scitranslmed.aaa4642","volume":"7","author":"JD Leverson","year":"2015","unstructured":"Leverson JD, Phillips DC, Mitten MJ, et al. Exploiting selective BCL-2 family inhibitors to dissect cell survival dependencies and define improved strategies for cancer therapy. Sci Transl Med. 2015;7:279ra40.","journal-title":"Sci Transl Med"},{"key":"4671_CR28","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1038\/nrd.2016.253","volume":"16","author":"A Ashkenazi","year":"2017","unstructured":"Ashkenazi A, Fairbrother WJ, Leverson JD, Souers AJ. From basic apoptosis discoveries to advanced selective BCL-2 family inhibitors. Nat Rev Drug Discov. 2017;16:273\u201384.","journal-title":"Nat Rev Drug Discov"},{"key":"4671_CR29","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1200\/JCO.2010.31.6208","volume":"29","author":"L Gandhi","year":"2011","unstructured":"Gandhi L, de Ribeiro Oliveira M, Bonomi P, et al. Phase I study of navitoclax (ABT-263), a novel Bcl-2 family inhibitor, in patients with small-cell lung cancer and other solid tumors. J Clin Oncol. 2011;29:909\u201316.","journal-title":"J Clin Oncol"},{"issue":"26","key":"4671_CR30","doi-asserted-by":"publisher","first-page":"4909","DOI":"10.1038\/s41388-020-1336-y","volume":"39","author":"S Khan","year":"2020","unstructured":"Khan S, He Y, Zhang X, et al. PROteolysis TArgeting Chimeras (PROTACs) as emerging anticancer therapeutics. Oncogene. 2020;39(26):4909\u201324.","journal-title":"Oncogene"},{"key":"4671_CR31","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1186\/s13045-020-00924-z","volume":"13","author":"Y He","year":"2020","unstructured":"He Y, Khan S, Huo Z, et al. Proteolysis targeting chimeras (PROTACs) are emerging therapeutics for hematologic malignancies. J Hematol Oncol. 2020;13:103.","journal-title":"J Hematol Oncol"},{"issue":"1","key":"4671_CR32","doi-asserted-by":"publisher","first-page":"7773","DOI":"10.1038\/s41467-025-62829-0","volume":"16","author":"M Steger","year":"2025","unstructured":"Steger M, Nishiguchi G, Wu Q, et al. Unbiased mapping of cereblon neosubstrate landscape by high-throughput proteomics. Nat Commun. 2025;16(1):7773.","journal-title":"Nat Commun"},{"key":"4671_CR33","doi-asserted-by":"publisher","first-page":"1966","DOI":"10.1002\/anie.201507978","volume":"55","author":"M Toure","year":"2016","unstructured":"Toure M, Crews CM. Small-molecule PROTACs: new approaches to protein degradation. Angew Chem Int Ed Engl. 2016;55:1966\u201373.","journal-title":"Angew Chem Int Ed Engl"},{"key":"4671_CR34","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1038\/nrd.2016.211","volume":"16","author":"AC Lai","year":"2017","unstructured":"Lai AC, Crews CM. Induced protein degradation: an emerging drug discovery paradigm. Nat Rev Drug Discov. 2017;16:101\u201314.","journal-title":"Nat Rev Drug Discov"},{"issue":"1","key":"4671_CR35","doi-asserted-by":"publisher","first-page":"1996","DOI":"10.1038\/s41467-020-15838-0","volume":"11","author":"Y He","year":"2020","unstructured":"He Y, Zhang X, Chang J, et al. Using proteolysis-targeting chimera technology to reduce navitoclax platelet toxicity and improve its senolytic activity. Nat Commun. 2020;11(1):1996.","journal-title":"Nat Commun"},{"issue":"5","key":"4671_CR36","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1038\/nrgastro.2016.51","volume":"13","author":"JM Banales","year":"2016","unstructured":"Banales JM, Cardinale V, Carpino G, et al. Expert consensus document: cholangiocarcinoma\u2014current knowledge and future perspectives. Nat Rev Gastroenterol Hepatol. 2016;13(5):261\u201380.","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"4671_CR37","doi-asserted-by":"publisher","first-page":"3282","DOI":"10.1038\/s41418-021-00816-w","volume":"28","author":"P Ramesh","year":"2021","unstructured":"Ramesh P, Lannagan TRM, Jackstadt R, et al. Bcl-xl is crucial for progression through the adenoma-to-carcinoma sequence of colorectal cancer. Cell Death Differ. 2021;28:3282\u201396.","journal-title":"Cell Death Differ"},{"key":"4671_CR38","doi-asserted-by":"publisher","first-page":"111826","DOI":"10.1016\/j.celrep.2022.111826","volume":"41","author":"V Bharti","year":"2022","unstructured":"Bharti V, Watkins R, Kumar A, et al. BCL-xL inhibition potentiates cancer therapies by redirecting the outcome of p53 activation from senescence to apoptosis. Cell Rep. 2022;41:111826.","journal-title":"Cell Rep"},{"key":"4671_CR39","doi-asserted-by":"publisher","first-page":"1421","DOI":"10.3389\/fonc.2019.01421","volume":"9","author":"JU Marquardt","year":"2019","unstructured":"Marquardt JU, Edlich F. Predisposition to apoptosis in hepatocellular carcinoma: from mechanistic insights to therapeutic strategies. Front Oncol. 2019;9:1421.","journal-title":"Front Oncol"},{"key":"4671_CR40","doi-asserted-by":"publisher","first-page":"2397","DOI":"10.1042\/BST20210750","volume":"49","author":"WD Fairlie","year":"2021","unstructured":"Fairlie WD, Lee EF. Targeting the BCL-2\u2013regulated apoptotic pathway for the treatment of solid cancers. Biochem Soc Trans. 2021;49:2397\u2013410.","journal-title":"Biochem Soc Trans"},{"key":"4671_CR41","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1038\/s41419-020-03092-7","volume":"11","author":"AL Scherr","year":"2020","unstructured":"Scherr AL, Mock A, Gdynia G, et al. Identification of BCL-XL as highly active survival factor and promising therapeutic target in colorectal cancer. Cell Death Dis. 2020;11:875.","journal-title":"Cell Death Dis"},{"key":"4671_CR42","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1038\/nm.4010","volume":"22","author":"J Chang","year":"2016","unstructured":"Chang J, Wang Y, Shao L, et al. Clearance of senescent cells by ABT-263 rejuvenates aged hematopoietic stem cells in mice. Nat Med. 2016;22:78\u201383.","journal-title":"Nat Med"},{"key":"4671_CR43","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1111\/acel.12445","volume":"15","author":"Y Zhu","year":"2016","unstructured":"Zhu Y, Tchkonia T, Fuhrmann-Stroissnigg H, et al. Identification of a novel senolytic agent, navitoclax, targeting the Bcl-2 family of anti-apoptotic factors. Aging Cell. 2016;15:428\u201335.","journal-title":"Aging Cell"},{"key":"4671_CR44","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1186\/s13045-020-00885-3","volume":"13","author":"X Li","year":"2020","unstructured":"Li X, Song Y. Proteolysis-targeting chimera (PROTAC) for targeted protein degradation and cancer therapy. J Hematol Oncol. 2020;13:50.","journal-title":"J Hematol Oncol"},{"key":"4671_CR45","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1471-2164-14-1","volume":"14","author":"PF Bray","year":"2013","unstructured":"Bray PF, McKenzie SE, Edelstein LC, et al. The complex transcriptional landscape of the anucleate human platelet. BMC Genomics. 2013;14:1.","journal-title":"BMC Genomics"},{"key":"4671_CR46","doi-asserted-by":"publisher","first-page":"1829","DOI":"10.1021\/acsmedchemlett.9b00568","volume":"11","author":"L Wang","year":"2020","unstructured":"Wang L, Doherty GA, Judd AS, et al. Discovery of a-1331852, a first-in-class, potent, and orally bioavailable BCL-X(L) inhibitor. ACS Med Chem Lett. 2020;11:1829\u201336.","journal-title":"ACS Med Chem Lett"},{"key":"4671_CR47","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/j.cell.2019.11.031","volume":"181","author":"GM Burslem","year":"2018","unstructured":"Burslem GM, Crews CM. Proteolysis-targeting chimeras as therapeutics and tools for biological discovery. Cell. 2018;181:102\u201314.","journal-title":"Cell"},{"key":"4671_CR48","doi-asserted-by":"publisher","first-page":"58","DOI":"10.3324\/haematol.2020.260331","volume":"107","author":"BZ Carter","year":"2022","unstructured":"Carter BZ, Mak PY, Tao W, et al. Targeting MCL-1 dysregulates cell metabolism and leukemia\u2013stroma interactions and resensitizes acute myeloid leukemia to BCL-2 inhibition. Haematologica. 2022;107:58\u201376.","journal-title":"Haematologica"},{"key":"4671_CR49","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.1038\/s42003-021-02564-6","volume":"4","author":"H Widden","year":"2021","unstructured":"Widden H, Placzek WJ. The multiple mechanisms of MCL1 in the regulation of cell fate. Commun Biol. 2021;4:1029.","journal-title":"Commun Biol"},{"issue":"31","key":"4671_CR50","doi-asserted-by":"publisher","first-page":"e202507702","DOI":"10.1002\/anie.202507702","volume":"64","author":"X Zhang","year":"2025","unstructured":"Zhang X, Song Z, Zhang X, et al. Unconventional PROTACs for targeted protein degradation in cancer therapy. Angew Chem Int Ed Engl. 2025;64(31):e202507702.","journal-title":"Angew Chem Int Ed Engl"},{"issue":"2","key":"4671_CR51","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1093\/annonc\/mdt540","volume":"25","author":"JW Valle","year":"2014","unstructured":"Valle JW, Furuse J, Jitlal M, et al. Cisplatin and gemcitabine for advanced biliary tract cancer: a meta-analysis of two randomised trials. Ann Oncol. 2014;25(2):391\u20138.","journal-title":"Ann Oncol"},{"issue":"4 Pt B","key":"4671_CR52","doi-asserted-by":"publisher","first-page":"1444","DOI":"10.1016\/j.bbadis.2017.06.005","volume":"1864","author":"JJG Marin","year":"2018","unstructured":"Marin JJG, Lozano E, Herraez E, et al. Chemoresistance and chemosensitization in cholangiocarcinoma. Biochim Biophys Acta. 2018;1864(4 Pt B):1444\u201353.","journal-title":"Biochim Biophys Acta"},{"key":"4671_CR53","doi-asserted-by":"publisher","first-page":"67754","DOI":"10.18632\/oncotarget.18834","volume":"8","author":"R Montano","year":"2017","unstructured":"Montano R, Khan N, Hou H, et al. Cell cycle perturbation induced by gemcitabine in human tumor cells in cell culture, xenografts and bladder cancer patients. Oncotarget. 2017;8:67754\u201368.","journal-title":"Oncotarget"},{"key":"4671_CR54","doi-asserted-by":"publisher","first-page":"3195","DOI":"10.21873\/invivo.12155","volume":"34","author":"D Namima","year":"2020","unstructured":"Namima D, Fujihara S, Iwama H, et al. The effect of gemcitabine on cell cycle arrest and microRNA signatures in pancreatic cancer cells. In Vivo. 2020;34:3195\u2013203.","journal-title":"In Vivo"},{"key":"4671_CR55","doi-asserted-by":"publisher","first-page":"1694","DOI":"10.1002\/ijc.35483","volume":"157","author":"W Mi","year":"2025","unstructured":"Mi W, van Tienderen GS, Shi S, et al. Apoptosis regulators of the Bcl-2 family play a key role in chemoresistance of cholangiocarcinoma organoids. Int J Cancer. 2025;157:1694\u2013708.","journal-title":"Int J Cancer"},{"key":"4671_CR56","doi-asserted-by":"publisher","first-page":"101143","DOI":"10.1016\/j.neo.2025.101143","volume":"62","author":"TV Steen","year":"2025","unstructured":"Steen TV, Espinoza I, Duran C, et al. Fatty acid synthase (FASN) inhibition cooperates with BH3 mimetic drugs to overcome resistance to mitochondrial apoptosis in pancreatic cancer. Neoplasia. 2025;62:101143.","journal-title":"Neoplasia"},{"key":"4671_CR57","doi-asserted-by":"publisher","first-page":"1176","DOI":"10.1158\/0008-5472.CAN-06-2203","volume":"67","author":"SK Tahir","year":"2007","unstructured":"Tahir SK, Yang X, Anderson MG, et al. Influence of Bcl-2 family members on the cellular response of small-cell lung cancer cell lines to ABT-737. Cancer Res. 2007;67:1176\u201383.","journal-title":"Cancer Res"}],"container-title":["BMC Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12916-026-04671-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12916-026-04671-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12916-026-04671-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T23:03:40Z","timestamp":1771974220000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12916-026-04671-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,30]]},"references-count":57,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["4671"],"URL":"https:\/\/doi.org\/10.1186\/s12916-026-04671-9","relation":{},"ISSN":["1741-7015"],"issn-type":[{"value":"1741-7015","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,30]]},"assertion":[{"value":"11 October 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 January 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 January 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Human samples were collected in accordance with the Declaration of Helsinki. The study was approved by the Ethics Committee of The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, and the Ethics Committee of the Kunming Institute of Zoology, Chinese Academy of Sciences (Approval No. KIZRKX-2025-SQ-046). Written informed consent was obtained from all participants.All animal experiments were approved by the Animal Ethics Committee of the Kunming Institute of Zoology, Chinese Academy of Sciences (IACUC-RE-2025-03-006) and conducted in accordance with the Guide for the Care and Use of Laboratory Animals. During the experiment, the maximum tumor volume in nude mice did not exceed the ethically permitted limit of 1500 mm\n                      3\n                      .","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"126"}}