{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T16:01:48Z","timestamp":1793289708142,"version":"4.5.0"},"reference-count":39,"publisher":"Elsevier BV","issue":"8","license":[{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T00:00:00Z","timestamp":1751500800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008349","name":"Boehringer Ingelheim GmbH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008349","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","esmoopen.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["ESMO Open"],"published-print":{"date-parts":[[2025,8]]},"DOI":"10.1016\/j.esmoop.2025.105540","type":"journal-article","created":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T00:31:29Z","timestamp":1753921889000},"page":"105540","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":3,"title":["Molecular profile and clinical impact of MDM2 amplification in patients with advanced biliary tract cancer"],"prefix":"10.1016","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-4502-8021","authenticated-orcid":false,"given":"H.","family":"Yoon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Jeong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3064-7895","authenticated-orcid":false,"given":"I.","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.-M.","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.O.","family":"Sung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.S.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.-Y.","family":"Ryoo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.-P.","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1451-8455","authenticated-orcid":false,"given":"C.","family":"Yoo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"10272","key":"10.1016\/j.esmoop.2025.105540_bib1","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1016\/S0140-6736(21)00153-7","article-title":"Biliary tract cancer","volume":"397","author":"Valle","year":"2021","journal-title":"Lancet"},{"issue":"9","key":"10.1016\/j.esmoop.2025.105540_bib2","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1038\/s41575-020-0310-z","article-title":"Cholangiocarcinoma 2020: the next horizon in mechanisms and management","volume":"17","author":"Banales","year":"2020","journal-title":"Nat Rev Gastroenterol Hepatol"},{"issue":"8","key":"10.1016\/j.esmoop.2025.105540_bib3","doi-asserted-by":"crossref","DOI":"10.1056\/EVIDoa2200015","article-title":"Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer","volume":"1","author":"Oh","year":"2022","journal-title":"NEJM Evid"},{"issue":"10391","key":"10.1016\/j.esmoop.2025.105540_bib4","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1016\/S0140-6736(23)00727-4","article-title":"Pembrolizumab in combination with gemcitabine and cisplatin compared with gemcitabine and cisplatin alone for patients with advanced biliary tract cancer (KEYNOTE-966): a randomised, double-blind, placebo-controlled, phase 3 trial","volume":"401","author":"Kelley","year":"2023","journal-title":"Lancet"},{"issue":"9","key":"10.1016\/j.esmoop.2025.105540_bib5","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1038\/ng.3375","article-title":"Genomic spectra of biliary tract cancer","volume":"47","author":"Nakamura","year":"2015","journal-title":"Nat Genet"},{"issue":"8","key":"10.1016\/j.esmoop.2025.105540_bib6","doi-asserted-by":"crossref","first-page":"2039","DOI":"10.3390\/cancers12082039","article-title":"Targeted therapies in advanced biliary tract cancer: an evolving paradigm","volume":"12","author":"Chakrabarti","year":"2020","journal-title":"Cancers (Basel)"},{"issue":"6","key":"10.1016\/j.esmoop.2025.105540_bib7","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1016\/S1470-2045(20)30157-1","article-title":"Ivosidenib in IDH1-mutant, chemotherapy-refractory cholangiocarcinoma (ClarIDHy): a multicentre, randomised, double-blind, placebo-controlled, phase 3 study","volume":"21","author":"Abou-Alfa","year":"2020","journal-title":"Lancet Oncol"},{"issue":"5","key":"10.1016\/j.esmoop.2025.105540_bib8","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/S1470-2045(20)30109-1","article-title":"Pemigatinib for previously treated, locally advanced or metastatic cholangiocarcinoma: a multicentre, open-label, phase 2 study","volume":"21","author":"Abou-Alfa","year":"2020","journal-title":"Lancet Oncol"},{"issue":"7","key":"10.1016\/j.esmoop.2025.105540_bib9","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1016\/S1470-2045(23)00242-5","article-title":"Zanidatamab for HER2-amplified, unresectable, locally advanced or metastatic biliary tract cancer (HERIZON-BTC-01): a multicentre, single-arm, phase 2b study","volume":"24","author":"Harding","year":"2023","journal-title":"Lancet Oncol"},{"key":"10.1016\/j.esmoop.2025.105540_bib10","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1200\/JCO.2023.41.4_suppl.531","article-title":"Characterization of long-term survivors in the TOPAZ-1 study of durvalumab or placebo plus gemcitabine and cisplatin in advanced biliary tract cancer","volume":"41","author":"Bouattour","year":"2023","journal-title":"J Clin Oncol"},{"issue":"6423","key":"10.1016\/j.esmoop.2025.105540_bib11","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1038\/362857a0","article-title":"Oncoprotein MDM2 conceals the activation domain of tumour suppressor p53","volume":"362","author":"Oliner","year":"1993","journal-title":"Nature"},{"issue":"1","key":"10.1016\/j.esmoop.2025.105540_bib12","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/cdd.2017.169","article-title":"How does p53 induce apoptosis and how does this relate to p53-mediated tumour suppression?","volume":"25","author":"Aubrey","year":"2018","journal-title":"Cell Death Differ"},{"issue":"3","key":"10.1016\/j.esmoop.2025.105540_bib13","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1124\/pharmrev.123.001026","article-title":"MDM2 inhibitors for cancer therapy: the past, present, and future","volume":"76","author":"Wang","year":"2024","journal-title":"Pharmacol Rev"},{"issue":"2","key":"10.1016\/j.esmoop.2025.105540_bib14","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/nrc3430","article-title":"MDM2, MDMX and p53 in oncogenesis and cancer therapy","volume":"13","author":"Wade","year":"2013","journal-title":"Nat Rev Cancer"},{"issue":"16","key":"10.1016\/j.esmoop.2025.105540_bib15","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.2217\/fon-2023-0963","article-title":"Brightline-2: a phase IIa\/IIb trial of brigimadlin (BI 907828) in advanced biliary tract cancer, pancreatic ductal adenocarcinoma or other solid tumors","volume":"20","author":"Yoo","year":"2024","journal-title":"Future Oncol"},{"issue":"11","key":"10.1016\/j.esmoop.2025.105540_bib16","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1101\/gr.239244.118","article-title":"Maftools: efficient and comprehensive analysis of somatic variants in cancer","volume":"28","author":"Mayakonda","year":"2018","journal-title":"Genome Res"},{"key":"10.1016\/j.esmoop.2025.105540_bib17","doi-asserted-by":"crossref","DOI":"10.1200\/PO.17.00011","article-title":"OncoKB: a precision oncology knowledge base","author":"Chakravarty","year":"2017","journal-title":"JCO Precis Oncol"},{"issue":"1","key":"10.1016\/j.esmoop.2025.105540_bib18","doi-asserted-by":"crossref","DOI":"10.1016\/j.esmoop.2024.104003","article-title":"ESMO Clinical Practice Guideline interim update on the management of biliary tract cancer","volume":"10","author":"Vogel","year":"2025","journal-title":"ESMO Open"},{"issue":"11","key":"10.1016\/j.esmoop.2025.105540_bib19","doi-asserted-by":"crossref","first-page":"2412","DOI":"10.1158\/2159-8290.CD-23-0669","article-title":"MRTX1719 is an MTA-cooperative PRMT5 inhibitor that exhibits synthetic lethality in preclinical models and patients with MTAP-deleted cancer","volume":"13","author":"Engstrom","year":"2023","journal-title":"Cancer Discov"},{"issue":"2","key":"10.1016\/j.esmoop.2025.105540_bib20","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.cell.2018.03.035","article-title":"Oncogenic signaling pathways in the cancer genome atlas","volume":"173","author":"Sanchez-Vega","year":"2018","journal-title":"Cell"},{"issue":"24","key":"10.1016\/j.esmoop.2025.105540_bib21","doi-asserted-by":"crossref","first-page":"2728","DOI":"10.1200\/JCO.19.02760","article-title":"Pathogenic germline mutations in DNA repair genes in combination with cancer treatment exposures and risk of subsequent neoplasms among long-term survivors of childhood cancer","volume":"38","author":"Qin","year":"2020","journal-title":"J Clin Oncol"},{"issue":"1","key":"10.1016\/j.esmoop.2025.105540_bib22","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/cr.2008.1","article-title":"Homologous recombination in DNA repair and DNA damage tolerance","volume":"18","author":"Li","year":"2008","journal-title":"Cell Res"},{"key":"10.1016\/j.esmoop.2025.105540_bib23","author":"Raghunathan"},{"issue":"suppl 4","key":"10.1016\/j.esmoop.2025.105540_bib24","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1200\/JCO.2025.43.4_suppl.544","article-title":"Real-world assessment of MDM2 amplification and survival among patients with advanced or metastatic biliary tract cancer in the United States","volume":"43","author":"Iyer","year":"2025","journal-title":"J Clin Oncol"},{"issue":"6","key":"10.1016\/j.esmoop.2025.105540_bib25","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1007\/s11523-024-01086-5","article-title":"The epidemiology of biliary tract cancer and associated prevalence of MDM2 amplification: a targeted literature review","volume":"19","author":"Kratz","year":"2024","journal-title":"Target Oncol"},{"issue":"4","key":"10.1016\/j.esmoop.2025.105540_bib26","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1097\/PAS.0000000000001006","article-title":"MDM2 amplification in intrahepatic cholangiocarcinomas: its relationship with large-duct type morphology and uncommon KRAS mutations","volume":"42","author":"Kim","year":"2018","journal-title":"Am J Surg Pathol"},{"issue":"1","key":"10.1016\/j.esmoop.2025.105540_bib27","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1186\/s12935-019-0937-4","article-title":"The role of MDM2 amplification and overexpression in therapeutic resistance of malignant tumors","volume":"19","author":"Hou","year":"2019","journal-title":"Cancer Cell Int"},{"issue":"3","key":"10.1016\/j.esmoop.2025.105540_bib28","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.lungcan.2003.09.010","article-title":"MDM2 gene amplification: a new independent factor of adverse prognosis in non-small cell lung cancer (NSCLC)","volume":"43","author":"Dworakowska","year":"2004","journal-title":"Lung Cancer"},{"key":"10.1016\/j.esmoop.2025.105540_bib29","doi-asserted-by":"crossref","DOI":"10.1016\/j.annonc.2020.08.1344","article-title":"1952P Comprehensive profiling of MDM2 amplified gastrointestinal (GI) cancers","volume":"31","author":"Battaglin","year":"2020","journal-title":"Ann Oncol"},{"issue":"9","key":"10.1016\/j.esmoop.2025.105540_bib30","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1101\/gad.886901","article-title":"ATM-dependent phosphorylation of Mdm2 on serine 395: role in p53 activation by DNA damage","volume":"15","author":"Maya","year":"2001","journal-title":"Genes Dev"},{"issue":"2","key":"10.1016\/j.esmoop.2025.105540_bib31","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1002\/(SICI)1096-9896(199806)185:2<188::AID-PATH53>3.0.CO;2-2","article-title":"Molecular abnormalities in liposarcoma: role of MDM2 and CDK4-containing amplicons at 12q13-22","volume":"185","author":"Pilotti","year":"1998","journal-title":"J Pathol"},{"issue":"2","key":"10.1016\/j.esmoop.2025.105540_bib32","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/S1535-6108(02)00102-2","article-title":"The RB and p53 pathways in cancer","volume":"2","author":"Sherr","year":"2002","journal-title":"Cancer Cell"},{"issue":"18","key":"10.1016\/j.esmoop.2025.105540_bib33","doi-asserted-by":"crossref","first-page":"5696","DOI":"10.1158\/1078-0432.CCR-08-3185","article-title":"Clinical and biological significance of CDK4 amplification in well-differentiated and dedifferentiated liposarcomas","volume":"15","author":"Italiano","year":"2009","journal-title":"Clin Cancer Res"},{"issue":"1","key":"10.1016\/j.esmoop.2025.105540_bib34","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-022-16455-1","article-title":"Amplification of CDK4 and MDM2: a detailed study of a high-risk neuroblastoma subgroup","volume":"12","author":"Martinez-Monleon","year":"2022","journal-title":"Sci Rep"},{"issue":"3","key":"10.1016\/j.esmoop.2025.105540_bib35","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1016\/j.jhep.2022.11.030","article-title":"Charting co-mutation patterns associated with actionable drivers in intrahepatic cholangiocarcinoma","volume":"78","author":"Kendre","year":"2023","journal-title":"J Hepatol"},{"issue":"10","key":"10.1016\/j.esmoop.2025.105540_bib36","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1038\/onc.2016.301","article-title":"Disruption of the RP-MDM2-p53 pathway accelerates APC loss-induced colorectal tumorigenesis","volume":"36","author":"Liu","year":"2017","journal-title":"Oncogene"},{"issue":"20","key":"10.1016\/j.esmoop.2025.105540_bib37","doi-asserted-by":"crossref","first-page":"11598","DOI":"10.1073\/pnas.181181198","article-title":"A phosphatidylinositol 3-kinase\/Akt pathway promotes translocation of Mdm2 from the cytoplasm to the nucleus","volume":"98","author":"Mayo","year":"2001","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"33","key":"10.1016\/j.esmoop.2025.105540_bib38","doi-asserted-by":"crossref","first-page":"53968","DOI":"10.18632\/oncotarget.16345","article-title":"MDM2 antagonists synergize with PI3K\/mTOR inhibition in well-differentiated\/dedifferentiated liposarcomas","volume":"8","author":"Laroche","year":"2017","journal-title":"Oncotarget"},{"key":"10.1016\/j.esmoop.2025.105540_bib39","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.ejca.2019.07.022","article-title":"Therapeutic relevance of targeted sequencing in management of patients with advanced biliary tract cancer: DNA damage repair gene mutations as a predictive biomarker","volume":"120","author":"Chae","year":"2019","journal-title":"Eur J Cancer"}],"container-title":["ESMO Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2059702925014097?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2059702925014097?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T08:11:31Z","timestamp":1777623091000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2059702925014097"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8]]},"references-count":39,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["S2059702925014097"],"URL":"https:\/\/doi.org\/10.1016\/j.esmoop.2025.105540","relation":{},"ISSN":["2059-7029"],"issn-type":[{"value":"2059-7029","type":"print"}],"subject":[],"published":{"date-parts":[[2025,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Molecular profile and clinical impact of MDM2 amplification in patients with advanced biliary tract cancer","name":"articletitle","label":"Article Title"},{"value":"ESMO Open","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.esmoop.2025.105540","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Author(s). Published by Elsevier Ltd on behalf of European Society for Medical Oncology.","name":"copyright","label":"Copyright"}],"article-number":"105540"}}