{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T13:08:06Z","timestamp":1790168886587,"version":"4.1.0"},"reference-count":304,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Med.","JCM"],"abstract":"<jats:p>Cholangiocarcinoma (CCA) remains an aggressive malignancy characterized by late-stage diagnosis, substantial molecular heterogeneity, and limited therapeutic options. Advances in molecular characterization have identified actionable alterations and expanded systemic treatment beyond conventional cytotoxic chemotherapy. This review examines three clinically relevant and mechanistically distinct targeted strategies in advanced CCA. Pemigatinib, a selective fibroblast growth factor receptor 1\u20133 (FGFR1\u20133) inhibitor, targets oncogenic signaling driven by FGFR2 fusions or rearrangements, which occur predominantly in intrahepatic CCA. Zanidatamab, a bispecific human epidermal growth factor receptor 2 (HER2)-directed antibody targeting two extracellular HER2 domains, provides a therapeutic approach for HER2-positive biliary tract cancers (BTCs). Ivosidenib, a selective inhibitor of mutant isocitrate dehydrogenase 1 (IDH1m), suppresses production of the oncometabolite D-2-hydroxyglutarate and targets the associated metabolic and epigenetic dysregulation in IDH1-mutant CCA. The review integrates the molecular rationale and pivotal clinical evidence supporting these therapies with their safety profiles, mechanisms of acquired resistance, biomarker selection, and therapeutic positioning. Particular attention is given to tumor heterogeneity and the tumor microenvironment as determinants of treatment response and resistance, as well as to emerging strategies involving next-generation inhibitors, antibody\u2013drug conjugates, immunotherapy, rational combinations, and longitudinal molecular monitoring. Collectively, the clinical development of pemigatinib, zanidatamab, and ivosidenib demonstrates the therapeutic value of matching actionable molecular alterations with mechanism-based treatments, while highlighting the need to overcome resistance and optimize treatment sequencing to achieve more durable benefit in advanced CCA.<\/jats:p>","DOI":"10.3390\/jcm15197396","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T12:36:07Z","timestamp":1790166967000},"page":"7396","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecularly Guided Therapy and the Tumor Microenvironment in Advanced Cholangiocarcinoma: Current Evidence and Emerging Strategies Targeting FGFR2, HER2, and IDH1 with Pemigatinib, Zanidatamab, and Ivosidenib"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3902-2744","authenticated-orcid":false,"given":"Piotr","family":"Kawczak","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Medical University of Gda\u0144sk, 80-416 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomasz","family":"B\u0105czek","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Medical University of Gda\u0144sk, 80-416 Gdansk, Poland"},{"name":"Department of Nursing and Medical Rescue, Institute of Health Sciences, Pomeranian University in S\u0142upsk, 76-200 Slupsk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1038\/s41575-020-0310-z","article-title":"CCA 2020: The next horizon in mechanisms and management","volume":"17","author":"Banales","year":"2020","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/nrclinonc.2017.157","article-title":"CCA\u2014Evolving concepts and therapeutic strategies","volume":"15","author":"Ilyas","year":"2018","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_3","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"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.jhep.2020.03.007","article-title":"Molecular targeted therapies: Ready for \u201cprime time\u201d in biliary tract cancer","volume":"73","author":"Lamarca","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/nrgastro.2016.51","article-title":"Expert Consensus Document: Cholangiocarcinoma: Current Knowledge and Future Perspectives Consensus Statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA)","volume":"13","author":"Banales","year":"2016","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1038\/s41572-021-00300-2","article-title":"Cholangiocarcinoma","volume":"7","author":"Brindley","year":"2021","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1111\/jgh.70357","article-title":"Intrahepatic Cholangiocarcinoma: Epidemiological Trends, Risk Factors, Diagnostic Challenges, and Advances in Personalized Therapy\u2014A Comprehensive Review","volume":"41","author":"Muhammad","year":"2026","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1016\/j.jhep.2014.01.021","article-title":"Guidelines for the diagnosis and management of intrahepatic CCA","volume":"60","author":"Bridgewater","year":"2014","journal-title":"J. Hepatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1111\/liv.14095","article-title":"CCA: Epidemiology and risk factors","volume":"39","author":"Khan","year":"2019","journal-title":"Liver Int."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1002\/hep.30289","article-title":"Intrahepatic CCA: Continuing challenges and translational advances","volume":"69","author":"Sirica","year":"2019","journal-title":"Hepatology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.jhep.2019.03.013","article-title":"Global trends in mortality from intrahepatic and extrahepatic CCA","volume":"71","author":"Bertuccio","year":"2019","journal-title":"J. Hepatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1056\/NEJMoa0908721","article-title":"Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer","volume":"362","author":"Valle","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1016\/S1470-2045(21)00027-9","article-title":"Second-line FOLFOX chemotherapy versus active symptom control for advanced biliary tract cancer (ABC-06): A phase 3, open-label, randomised, controlled trial","volume":"22","author":"Lamarca","year":"2021","journal-title":"Lancet Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"EVIDoa2200015","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."},{"key":"ref_15","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"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1080\/13543784.2021.1897102","article-title":"Durvalumab: An investigational anti-PD-L1 antibody for the treatment of biliary tract cancer","volume":"30","author":"Rizzo","year":"2021","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_17","first-page":"81","article-title":"Biologics, Immunotherapy, and Future Directions in the Treatment of Advanced Cholangiocarcinoma","volume":"18","author":"Saeed","year":"2019","journal-title":"Clin. Color. Cancer"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Massironi, S., Pilla, L., Elvevi, A., Longarini, R., Rossi, R.E., Bidoli, P., and Invernizzi, P. (2020). New and Emerging Systemic Therapeutic Options for Advanced Cholangiocarcinoma. Cells, 9.","DOI":"10.3390\/cells9030688"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1016\/j.hoc.2026.05.006","article-title":"Systemic Therapy for Biliary and Liver Neoplasms: Chemotherapy and Immunotherapy","volume":"40","author":"McLaughlin","year":"2026","journal-title":"Hematol. Oncol. Clin. N. Am."},{"key":"ref_20","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."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4154","DOI":"10.1158\/1078-0432.CCR-18-0078","article-title":"Comprehensive molecular profiling of intrahepatic and extrahepatic CCAs: Potential targets for intervention","volume":"24","author":"Lowery","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1158\/2159-8290.CD-17-0368","article-title":"Whole-genome and epigenomic landscapes of etiologically distinct subtypes of CCA","volume":"7","author":"Jusakul","year":"2017","journal-title":"Cancer Discov."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.jhep.2020.03.008","article-title":"Molecular classification and therapeutic targets in extrahepatic CCA","volume":"73","author":"Montal","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_24","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 CCA: A multicentre, open-label, phase 2 study","volume":"21","author":"Sahai","year":"2020","journal-title":"Lancet Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1200\/JCO.2017.75.5009","article-title":"Phase II study of BGJ398 in patients with FGFR-altered advanced CCA","volume":"36","author":"Javle","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1056\/NEJMoa2206834","article-title":"Futibatinib for FGFR2-rearranged intrahepatic CCA","volume":"388","author":"Goyal","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1158\/2159-8290.CD-20-0766","article-title":"Clinicogenomic analysis of FGFR2-rearranged CCA identifies correlates of response and mechanisms of resistance to pemigatinib","volume":"11","author":"Silverman","year":"2021","journal-title":"Cancer Discov."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.1016\/j.humpath.2014.03.014","article-title":"Fibroblast growth factor receptor 2 translocations in intrahepatic CCA","volume":"45","author":"Graham","year":"2014","journal-title":"Hum. Pathol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1002\/hep.26890","article-title":"Fibroblast growth factor receptor 2 tyrosine kinase fusions define a unique molecular subtype of CCA","volume":"59","author":"Arai","year":"2014","journal-title":"Hepatology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1634\/theoncologist.2013-0352","article-title":"New routes to targeted therapy of intrahepatic CCAs revealed by next-generation sequencing","volume":"19","author":"Ross","year":"2014","journal-title":"Oncologist"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Borad, M.J., Champion, M.D., Egan, J.B., Liang, W.S., Fonseca, R., Bryce, A.H., McCullough, A.E., Barrett, M.T., Hunt, K., and Patel, M.D. (2014). Integrated genomic characterization reveals novel, therapeutically relevant drug targets in FGFR and EGFR pathways in sporadic intrahepatic CCA. PLoS Genet., 10.","DOI":"10.1371\/journal.pgen.1004135"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2607","DOI":"10.2217\/fon-2023-0098","article-title":"Molecular Targeted and Systemic Therapy for Intrahepatic Cholangiocarcinoma: A Multi-Disciplinary Approach","volume":"19","author":"Merath","year":"2023","journal-title":"Future Oncol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"555","DOI":"10.21037\/hbsn-20-396","article-title":"Cholangiocarcinoma: A Review of the Literature and Future Directions in Therapy","volume":"11","author":"Halder","year":"2022","journal-title":"HepatoBiliary Surg. Nutr."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1038\/nrc2780","article-title":"Fibroblast growth factor signalling: From development to cancer","volume":"10","author":"Turner","year":"2010","journal-title":"Nat. Rev. Cancer"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1038\/nrc.2017.8","article-title":"Advances and challenges in targeting FGFR signalling in cancer","volume":"17","author":"Babina","year":"2017","journal-title":"Nat. Rev. Cancer"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1158\/1535-7163.MCT-19-0631","article-title":"Efficacy of FGFR inhibitors and combination therapies for acquired resistance in FGFR2-fusion CCA","volume":"19","author":"Krook","year":"2020","journal-title":"Mol. Cancer Ther."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"699","DOI":"10.21037\/jgo-2024-923","article-title":"Safety and efficacy of pemigatinib in patients with CCA: A systematic review","volume":"16","author":"Rasool","year":"2025","journal-title":"J. Gastrointest. Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1158\/2159-8290.CD-17-0245","article-title":"New horizons for precision medicine in biliary tract cancers","volume":"7","author":"Valle","year":"2017","journal-title":"Cancer Discov."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1002\/jhbp.65","article-title":"Potential Targeted Therapy for Liver Fluke Associated Cholangiocarcinoma","volume":"21","author":"Vaeteewoottacharn","year":"2014","journal-title":"J. Hepato-Biliary-Pancreat. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1186\/s13045-015-0155-z","article-title":"HER2\/neu-Directed Therapy for Biliary Tract Cancer","volume":"8","author":"Javle","year":"2015","journal-title":"J. Hematol. Oncol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1007\/s10555-016-9645-x","article-title":"HER2\/HER3 Pathway in Biliary Tract Malignancies; Systematic Review and Meta-Analysis: A Potential Therapeutic Target?","volume":"36","author":"Galdy","year":"2017","journal-title":"Cancer Metastasis Rev."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1038\/nrc3309","article-title":"The ERBB Network: At Last, Cancer Therapy Meets Systems Biology","volume":"12","author":"Yarden","year":"2012","journal-title":"Nat. Rev. Cancer"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2033","DOI":"10.1158\/1078-0432.CCR-18-2275","article-title":"Advances in HER2-Targeted Therapy: Novel Agents and Opportunities Beyond Breast and Gastric Cancer","volume":"25","author":"Johnson","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1016\/S1470-2045(21)00336-3","article-title":"Pertuzumab and Trastuzumab for HER2-Positive, Metastatic Biliary Tract Cancer (MyPathway): A Multicentre, Open-Label, Phase 2a, Multiple Basket Study","volume":"22","author":"Javle","year":"2021","journal-title":"Lancet Oncol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.1016\/S1470-2045(22)00621-0","article-title":"Zanidatamab, a Novel Bispecific Antibody, for the Treatment of Locally Advanced or Metastatic HER2-Expressing or HER2-Amplified Cancers: A Phase 1, Dose-Escalation and Expansion Study","volume":"23","author":"Beeram","year":"2022","journal-title":"Lancet Oncol."},{"key":"ref_46","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":"ref_47","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/s41571-019-0268-3","article-title":"HER2-Targeted Therapies\u2014A Role Beyond Breast Cancer","volume":"17","author":"Oh","year":"2020","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2780","DOI":"10.1016\/j.celrep.2017.02.033","article-title":"Integrative Genomic Analysis of CCA Identifies Distinct IDH-Mutant Molecular Profiles","volume":"18","author":"Farshidfar","year":"2017","journal-title":"Cell Rep."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1038\/nature08617","article-title":"Cancer-Associated IDH1 Mutations Produce 2-Hydroxyglutarate","volume":"462","author":"Dang","year":"2009","journal-title":"Nature"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1007\/s00280-023-04633-5","article-title":"Pharmacokinetics\/pharmacodynamics of ivosidenib in advanced IDH1-mutant CCA: Findings from the phase III ClarIDHy study","volume":"93","author":"Fan","year":"2024","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.1001\/jamaoncol.2021.3836","article-title":"Final Overall Survival Efficacy Results of Ivosidenib for Patients with Advanced CCA with IDH1 Mutation: The Phase 3 Randomized Clinical ClarIDHy Trial","volume":"7","author":"Zhu","year":"2021","journal-title":"JAMA Oncol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1016\/S2468-1253(19)30189-X","article-title":"Safety and Activity of Ivosidenib in Patients with IDH1-Mutant Advanced CCA: A Phase 1 Study","volume":"4","author":"Lowery","year":"2019","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1200\/JCO.19.02105","article-title":"Efficacy of Pembrolizumab in Patients with Noncolorectal High Microsatellite Instability\/Mismatch Repair\u2013Deficient Cancer: Results from the Phase II KEYNOTE-158 Study","volume":"38","author":"Marabelle","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1007\/s11523-025-01142-8","article-title":"Efficacy and Toxicity of Pemigatinib in Advanced CCA Harboring FGFR Fusions or Rearrangements: A Systematic Review and Meta-Analysis","volume":"20","author":"Akkus","year":"2025","journal-title":"Target. Oncol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1158\/2159-8290.CD-16-1000","article-title":"Polyclonal Secondary FGFR2 Mutations Drive Acquired Resistance to FGFR Inhibition in Patients with FGFR2 Fusion-Positive CCA","volume":"7","author":"Goyal","year":"2017","journal-title":"Cancer Discov."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"4861","DOI":"10.1038\/onc.2012.617","article-title":"Intrahepatic CCA: Pathogenesis and Rationale for Molecular Therapies","volume":"32","author":"Sia","year":"2013","journal-title":"Oncogene"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1158\/1078-0432.CCR-14-3296","article-title":"Molecular Pathogenesis and Targeted Therapies for Intrahepatic CCA","volume":"22","author":"Moeini","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_58","first-page":"100335","article-title":"First-Line Chemotherapy in Advanced Biliary Tract Cancer Ten Years After the ABC-02 Trial: \u201cAnd Yet It Moves!\u201d","volume":"27","author":"Rizzo","year":"2021","journal-title":"Cancer Treat. Res. Commun."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.1136\/gutjnl-2022-327099","article-title":"Clinical Relevance of Biomarkers in CCA: Critical Revision and Future Directions","volume":"71","author":"Macias","year":"2022","journal-title":"Gut"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1111\/apt.70769","article-title":"Review Article: Systemic Treatments for Advanced CCA\u2014State of the Art and Future Directions","volume":"64","author":"Qi","year":"2026","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2716","DOI":"10.1200\/JCO.21.02576","article-title":"Precision Medicine in Biliary Tract Cancer","volume":"40","author":"Scott","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/s41575-022-00741-4","article-title":"Immunology and Immunotherapy of Cholangiocarcinoma","volume":"20","author":"Greten","year":"2023","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.jhep.2019.10.009","article-title":"Systemic Therapies for Intrahepatic CCA","volume":"72","author":"Kelley","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e515","DOI":"10.1016\/S1470-2045(20)30554-4","article-title":"Dabrafenib plus Trametinib in Patients with BRAFV600E-Mutated Biliary Tract Cancer","volume":"21","author":"Dekker","year":"2020","journal-title":"Lancet Oncol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1016\/S1470-2045(20)30445-9","article-title":"Association of Tumour Mutational Burden with Outcomes in Patients with Advanced Solid Tumours Treated with Pembrolizumab: Prospective Biomarker Analysis of the Multicohort, Open-Label, Phase 2 KEYNOTE-158 Study","volume":"21","author":"Marabelle","year":"2020","journal-title":"Lancet Oncol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1200\/JCO.2017.75.3780","article-title":"Targeted Therapy for Advanced Solid Tumors on the Basis of Molecular Profiles: Results from MyPathway, an Open-Label, Phase IIa Multiple Basket Study","volume":"36","author":"Hainsworth","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1177\/10781552231171079","article-title":"Updates in the Use of Targeted Therapies for the Treatment of CCA","volume":"29","author":"Lodl","year":"2023","journal-title":"J. Oncol. Pharm. Pract."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1038\/s41591-019-0561-9","article-title":"Liquid versus Tissue Biopsy for Detecting Acquired Resistance and Tumor Heterogeneity in Gastrointestinal Cancers","volume":"25","author":"Parikh","year":"2019","journal-title":"Nat. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"107875","DOI":"10.5306\/wjco.v16.i10.107875","article-title":"Circulating Tumor DNA in Biliary Tract Cancers: A Review of Current Applications","volume":"16","author":"Teixeira","year":"2025","journal-title":"World J. Clin. Oncol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1038\/s41571-021-00560-7","article-title":"Predicting Cancer Outcomes with Radiomics and Artificial Intelligence in Radiology","volume":"19","author":"Bera","year":"2022","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1038\/s41575-020-0343-3","article-title":"Development of AI-Based Pathology Biomarkers in Gastrointestinal and Liver Cancer","volume":"17","author":"Kather","year":"2020","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"104235","DOI":"10.1016\/j.critrevonc.2023.104235","article-title":"Immunotherapy and Targeted Therapy for Cholangiocarcinoma: Artificial Intelligence Research in Imaging","volume":"194","author":"Liu","year":"2024","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/s11864-023-01153-5","article-title":"Current Standards, Multidisciplinary Approaches, and Future Directions in the Management of Extrahepatic Cholangiocarcinoma","volume":"25","author":"Wheless","year":"2024","journal-title":"Curr. Treat. Options Oncol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.hoc.2026.05.003","article-title":"Transhepatic Biliary Intervention for Malignant Biliary Obstruction","volume":"40","author":"Mastria","year":"2026","journal-title":"Hematol. Oncol. Clin. N. Am."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2684","DOI":"10.1158\/1078-0432.CCR-14-2329","article-title":"Targeting FGFR Signaling in Cancer","volume":"21","author":"Touat","year":"2015","journal-title":"Clin. Cancer Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1158\/1078-0432.CCR-14-3212","article-title":"The FGFR Landscape in Cancer: Analysis of 4,853 Tumors by Next-Generation Sequencing","volume":"22","author":"Helsten","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1093\/jjco\/hyaf162","article-title":"Remarkable response of gastric adenocarcinoma with FGFR2-TRIM44 fusion to pemigatinib: A case report","volume":"56","author":"Fujiwara","year":"2026","journal-title":"Jpn. J. Clin. Oncol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"797","DOI":"10.21037\/jgo.2016.09.01","article-title":"Molecular Profiling of Biliary Tract Cancer: A Target-Rich Disease","volume":"7","author":"Jain","year":"2016","journal-title":"J. Gastrointest. Oncol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"3","DOI":"10.3892\/ijmm.2016.2620","article-title":"FGFR Inhibitors: Effects on Cancer Cells, Tumor Microenvironment and Whole-Body Homeostasis (Review)","volume":"38","author":"Katoh","year":"2016","journal-title":"Int. J. Mol. Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.annonc.2022.10.506","article-title":"Biliary Tract Cancer: ESMO Clinical Practice Guideline for Diagnosis, Treatment and Follow-Up","volume":"34","author":"Vogel","year":"2023","journal-title":"Ann. Oncol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"389","DOI":"10.2217\/fon-2020-0726","article-title":"Pemigatinib, a potent inhibitor of FGFRs for the treatment of cholangiocarcinoma","volume":"17","author":"Merz","year":"2021","journal-title":"Future Oncol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"17562848221115317","DOI":"10.1177\/17562848221115317","article-title":"Pemigatinib for adults with previously treated, locally advanced or metastatic cholangiocarcinoma with FGFR2 fusions\/rearrangements","volume":"15","author":"Walden","year":"2022","journal-title":"Ther. Adv. Gastroenterol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1080\/14737140.2022.2150168","article-title":"Pemigatinib in cholangiocarcinoma with a FGFR2 rearrangement or fusion","volume":"22","author":"Storandt","year":"2022","journal-title":"Expert Rev. Anticancer Ther."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"4915","DOI":"10.1007\/s00432-022-04428-w","article-title":"Sustained response on sequential anti-FGFR therapy in metastatic gall bladder cancer: A case report and literature review","volume":"149","author":"Sheth","year":"2023","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"6087","DOI":"10.1038\/ncomms7087","article-title":"Massive Parallel Sequencing Uncovers Actionable FGFR2-PPHLN1 Fusion and ARAF Mutations in Intrahepatic CCA","volume":"6","author":"Sia","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"4888","DOI":"10.1158\/1078-0432.CCR-18-3334","article-title":"Multicenter Phase I Study of Erdafitinib (JNJ-42756493), Oral Pan-Fibroblast Growth Factor Receptor Inhibitor, in Patients with Advanced or Refractory Solid Tumors","volume":"25","author":"Bahleda","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Chmiel, P., G\u0119ca, K., Rawicz-Pruszy\u0144ski, K., Polkowski, W.P., and Sk\u00f3rzewska, M. (2022). FGFR Inhibitors in CCA\u2014A Novel Yet Primary Approach: Where Do We Stand Now and Where to Head Next in Targeting This Axis?. Cells, 11.","DOI":"10.3390\/cells11233929"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1038\/s42004-022-00718-z","article-title":"Characterization of the cholangiocarcinoma drug pemigatinib against FGFR gatekeeper mutants","volume":"5","author":"Lin","year":"2022","journal-title":"Commun. Chem."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"103488","DOI":"10.1016\/j.esmoop.2024.103488","article-title":"An Open-Label Study of Pemigatinib in CCA: Final Results from FIGHT-202","volume":"9","author":"Vogel","year":"2024","journal-title":"ESMO Open"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/S2468-1253(21)00196-5","article-title":"Infigratinib (BGJ398) in Previously Treated Patients with Advanced or Metastatic CCA with FGFR2 Fusions or Rearrangements: Mature Results from a Multicentre, Open-Label, Single-Arm, Phase 2 Study","volume":"6","author":"Javle","year":"2021","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"7925","DOI":"10.3390\/curroncol29100626","article-title":"Pemigatinib in intrahepatic cholangiocarcinoma: A work in progress","volume":"29","author":"Rizzo","year":"2022","journal-title":"Curr. Oncol."},{"key":"ref_92","first-page":"200","article-title":"Advanced Intrahepatic CCA: Post Hoc Analysis of the ABC-01, -02, and -03 Clinical Trials","volume":"112","author":"Lamarca","year":"2020","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2385","DOI":"10.2217\/fon-2020-0429","article-title":"FIGHT-302: First-Line Pemigatinib vs Gemcitabine Plus Cisplatin for Advanced CCA with FGFR2 Rearrangements","volume":"16","author":"Valle","year":"2020","journal-title":"Future Oncol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2187","DOI":"10.1200\/JCO-26-00788","article-title":"Pemigatinib for Unresectable or Metastatic Cholangiocarcinoma with Fibroblast Growth Factor Receptor-2 Rearrangement: Results from the Phase III FIGHT-302 Trial","volume":"44","author":"Melisi","year":"2026","journal-title":"J. Clin. Oncol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"102170","DOI":"10.1016\/j.ctrv.2021.102170","article-title":"Targeting FGFR Inhibition in CCA","volume":"95","author":"Goyal","year":"2021","journal-title":"Cancer Treat. Rev."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1080\/17474124.2021.1853527","article-title":"Recent Advances of Immunotherapy for Biliary Tract Cancer","volume":"15","author":"Rizzo","year":"2021","journal-title":"Expert Rev. Gastroenterol. Hepatol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1007\/s10637-026-01602-6","article-title":"Phase I results of a multicenter, open-label, dose de-escalation and expansion study of gemcitabine and cisplatin with ivosidenib or pemigatinib for advanced cholangiocarcinoma","volume":"44","author":"Saj","year":"2026","journal-title":"Investig. New Drugs"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1158\/2159-8290.CD-19-0182","article-title":"TAS-120 Overcomes Resistance to ATP-Competitive FGFR Inhibitors in Patients with FGFR2 Fusion-Positive Intrahepatic CCA","volume":"9","author":"Goyal","year":"2019","journal-title":"Cancer Discov."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"441","DOI":"10.21873\/cgp.20203","article-title":"Circulating Tumor DNA in Biliary Tract Cancer: Current Evidence and Future Perspectives","volume":"17","author":"Rizzo","year":"2020","journal-title":"Cancer Genom. Proteom."},{"key":"ref_100","first-page":"100337","article-title":"Pemigatinib: Hot Topics Behind the First Approval of a Targeted Therapy in CCA","volume":"27","author":"Rizzo","year":"2021","journal-title":"Cancer Treat. Res. Commun."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1093\/annonc\/mdx650","article-title":"Monitoring Resistance through Liquid Biopsy","volume":"29","author":"Parikh","year":"2018","journal-title":"Ann. Oncol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1038\/s41416-020-01157-0","article-title":"Fibroblast Growth Factor Receptors in Cancer: Genetic Alterations, Diagnostics, Therapeutic Targets and Mechanisms of Resistance","volume":"124","author":"Krook","year":"2021","journal-title":"Br. J. Cancer"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/s41419-025-07804-9","article-title":"Targeting the ROCK2\/UBA52\/DRP1 axis enhances ferroptosis and overcomes pemigatinib resistance in cholangiocarcinoma","volume":"16","author":"Zhang","year":"2025","journal-title":"Cell Death Dis."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1038\/s41419-026-08574-8","article-title":"N6-methyladenosine-mediated up-regulation of ARRB2 regulates intrahepatic cholangiocarcinoma malignant progression and pemigatinib resistance through MAPK and Hippo signaling pathways","volume":"17","author":"Chen","year":"2026","journal-title":"Cell Death Dis."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"3044","DOI":"10.1007\/s10620-026-09720-0","article-title":"VPS33A promotes pemigatinib resistance in cholangiocarcinoma via autophagy","volume":"71","author":"Chen","year":"2026","journal-title":"Dig. Dis. Sci."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Xin, X., and Miao, R. (2026). FGFR2-rearranged biliary tract cancer: Biology, resistance mechanisms, and emerging therapeutic strategies. Cancers, 18.","DOI":"10.3390\/cancers18030531"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Nishida, N., Aoki, T., Morita, M., Chishina, H., Takita, M., Ida, H., Hagiwara, S., Minami, Y., Ueshima, K., and Kudo, M. (2023). Non-Inflamed Tumor Microenvironment and Methylation\/Downregulation of Antigen-Presenting Machineries in Cholangiocarcinoma. Cancers, 15.","DOI":"10.3390\/cancers15082379"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"4185","DOI":"10.3390\/curroncol30040319","article-title":"Cancer-Associated Fibroblasts and Extracellular Matrix: Therapeutical Strategies for Modulating the Cholangiocarcinoma Microenvironment","volume":"30","author":"Minini","year":"2023","journal-title":"Curr. Oncol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/bs.acr.2022.01.009","article-title":"Cancer-Associated Fibroblasts in Intrahepatic Cholangiocarcinoma Progression and Therapeutic Resistance","volume":"156","author":"Ravichandra","year":"2022","journal-title":"Adv. Cancer Res."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"4943","DOI":"10.1158\/1078-0432.CCR-24-1834","article-title":"Understanding and Overcoming Resistance to Selective FGFR Inhibitors across FGFR2-Driven Malignancies","volume":"30","author":"Facchinetti","year":"2024","journal-title":"Clin. Cancer Res."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"2012","DOI":"10.1158\/2159-8290.CD-23-0475","article-title":"RLY-4008, the First Highly Selective FGFR2 Inhibitor with Activity across FGFR2 Alterations and Resistance Mutations","volume":"13","author":"Subbiah","year":"2023","journal-title":"Cancer Discov."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"e2317756121","DOI":"10.1073\/pnas.2317756121","article-title":"Discovery of Lirafugratinib (RLY-4008), a Highly Selective Irreversible Small-Molecule Inhibitor of FGFR2","volume":"121","author":"Ayaz","year":"2024","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1016\/j.annonc.2026.01.004","article-title":"Mechanisms of Clinical Resistance to Selective FGFR2 Inhibition by Lirafugratinib","volume":"37","author":"Ellis","year":"2026","journal-title":"Ann. Oncol."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"He, Z., Chen, Y., Li, G., Wang, J., Wang, Y., Tu, P., Huang, Y., Zhao, L., Pan, X., and Liu, H. (2026). FGFR Aberrations in Solid Tumors: Mechanistic Insights and Clinical Translation of Targeted Therapies. Cancers, 18.","DOI":"10.3390\/cancers18010089"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1645","DOI":"10.1038\/s41591-024-02934-7","article-title":"Pemigatinib in Previously Treated Solid Tumors with Activating FGFR1\u2013FGFR3 Alterations: Phase 2 FIGHT-207 Basket Trial","volume":"30","author":"Damian","year":"2024","journal-title":"Nat. Med."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"103625","DOI":"10.1016\/j.esmoop.2024.103625","article-title":"Open-Label, Dose-Escalation FIGHT-101 Study of Pemigatinib Combined with Targeted Therapy, Chemotherapy, or Immunotherapy in Patients with Advanced Malignancies","volume":"9","author":"Saleh","year":"2024","journal-title":"ESMO Open"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1002\/hep.31092","article-title":"Identification of Four Immune Subtypes Characterized by Distinct Composition and Functions of Tumor Microenvironment in Intrahepatic CCA","volume":"72","author":"Job","year":"2020","journal-title":"Hepatology"},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Cillis, J., Chen, C., Deshpande, S., Fong, Y., and Chaurasiya, S. (2026). Current Status of Drug Treatment of CCA\u2014Updated Progress and Critical Limitations. Pharmaceuticals, 19.","DOI":"10.3390\/ph19040554"},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Yang, Y., Li, J., Ma, D., Hao, F., Li, W., Xie, J., Qian, L., Wang, J., and Chen, Y. (2025). Systemic therapy with pemigatinib and sintilimab followed by resection for recurrent FGFR-2-positive intrahepatic cholangiocarcinoma: A case report. Front. Oncol., 15.","DOI":"10.3389\/fonc.2025.1527372"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1007\/s11523-023-01024-x","article-title":"Pemigatinib: A Review in Advanced CCA","volume":"19","author":"Frampton","year":"2024","journal-title":"Target. Oncol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1007\/s40265-020-01330-y","article-title":"Pemigatinib: First Approval","volume":"80","author":"Hoy","year":"2020","journal-title":"Drugs"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1177\/1078155220983425","article-title":"Fibroblast Growth Factor Receptor (FGFR) Inhibitors: A Review of a Novel Therapeutic Class","volume":"27","author":"Weaver","year":"2021","journal-title":"J. Oncol. Pharm. Pract."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.annonc.2020.11.005","article-title":"Prevention and Management of Dermatological Toxicities Related to Anticancer Agents: ESMO Clinical Practice Guidelines","volume":"32","author":"Lacouture","year":"2021","journal-title":"Ann. Oncol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1080\/14740338.2023.2227561","article-title":"A drug safety evaluation of pemigatinib for advanced cholangiocarcinoma","volume":"22","author":"Uson","year":"2023","journal-title":"Expert Opin. Drug Saf."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1097\/ICB.0000000000001468","article-title":"Subretinal fluid associated with pemigatinib therapy for cholangiocarcinoma: A case report and literature review","volume":"18","author":"Caranfa","year":"2024","journal-title":"Retin. Cases Brief. Rep."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"263","DOI":"10.36849\/JDD.9496","article-title":"Management of nail toxicities from fibroblast growth factor receptor inhibitors","volume":"25","author":"Patel","year":"2026","journal-title":"J. Drugs Dermatol."},{"key":"ref_127","first-page":"e108439","article-title":"Pemigatinib-associated psoriasis in a patient with cholangiocarcinoma","volume":"18","author":"Hendrie","year":"2026","journal-title":"Cureus"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"e2100511","DOI":"10.1200\/PO.21.00511","article-title":"FGFR Inhibitors in CCA: A Real-World Experience at a Tertiary Center","volume":"6","author":"Rizzo","year":"2022","journal-title":"JCO Precis. Oncol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"2328","DOI":"10.1093\/annonc\/mdu162","article-title":"Second-Line Chemotherapy in Advanced Biliary Cancer: A Systematic Review","volume":"25","author":"Lamarca","year":"2014","journal-title":"Ann. Oncol."},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Ding, P.Q., Tam, V.C., Ramjeesingh, R., Asselah, J., Sheffield, B.S., Mitchell, T., Gaudreau, A.J., Knox, J.J., and Cheung, W.Y. (2025). Pemigatinib in the real-world management of cholangiocarcinoma through a Canadian patient support program. Curr. Oncol., 32.","DOI":"10.3390\/curroncol32070405"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"100704","DOI":"10.1016\/j.esmorw.2026.100704","article-title":"Real-world patient characteristics and utilization patterns in patients with cholangiocarcinoma who received pemigatinib in the United States of America","volume":"12","author":"Verma","year":"2026","journal-title":"ESMO Real-World Data Digit. Oncol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/s12962-025-00713-w","article-title":"Battle against time for innovative cancer treatment: An updated cost-effectiveness analysis of pemigatinib in intrahepatic cholangiocarcinoma","volume":"24","author":"Wang","year":"2026","journal-title":"Cost Eff. Resour. Alloc."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"oyaf352","DOI":"10.1093\/oncolo\/oyaf352","article-title":"Economic and clinical outcomes among patients with cholangiocarcinoma receiving pemigatinib with or without history of cancer of unknown primary","volume":"30","author":"Verma","year":"2025","journal-title":"Oncologist"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"403","DOI":"10.6004\/jnccn.2025.0042","article-title":"Biliary Tract Cancers, Version 2.2025, NCCN Clinical Practice Guidelines in Oncology","volume":"23","author":"Benson","year":"2025","journal-title":"J. Natl. Compr. Cancer Netw."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1007\/s13402-026-01190-w","article-title":"Single-cell transcriptomic mapping of patient-derived primary liver cancer organoids reveals molecular subtypes and guides precision drug targeting","volume":"49","author":"Dai","year":"2026","journal-title":"Cell. Oncol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1080\/1120009X.2025.2497641","article-title":"Exposure-response analyses of pemigatinib in patients with myeloid\/lymphoid neoplasms with fibroblast growth factor receptor 1 rearrangement","volume":"38","author":"Gong","year":"2026","journal-title":"J. Chemother."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1038\/s41420-025-02844-8","article-title":"FGF1-FGFR2 axis regulated by nuclear receptor ROR\u03b3 represents an effective strategy in intrahepatic cholangiocarcinoma","volume":"11","author":"Gu","year":"2025","journal-title":"Cell Death Discov."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/S2468-1253(25)00230-4","article-title":"Tinengotinib for adults with advanced or metastatic cholangiocarcinoma: A multicentre, open-label, phase 2 trial","volume":"11","author":"Javle","year":"2026","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1007\/s40487-025-00371-1","article-title":"Sequential fibroblast growth factor receptor inhibition in intrahepatic cholangiocarcinoma: Navigating an evolving landscape of resistance and opportunity\u2014A case report and current opinion","volume":"13","author":"Sasanuma","year":"2025","journal-title":"Oncol. Ther."},{"key":"ref_140","unstructured":"(2026, August 08). Pemazyre\u00ae (Pemigatinib) Prescribing Information. U.S. Food and Drug Administration, Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2022\/213736s002lbl.pdf."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"113587","DOI":"10.1016\/j.ejca.2024.113587","article-title":"Pemigatinib for Patients with Previously Treated, Locally Advanced or Metastatic CCA Harboring FGFR2 Fusions or Rearrangements: A Joint Analysis of the French PEMI-BIL and Italian PEMI-REAL Cohort Studies","volume":"200","author":"Parisi","year":"2024","journal-title":"Eur. J. Cancer"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"55","DOI":"10.21037\/cco-23-72","article-title":"Targeting ERBB2\/HER2 Genetic Alterations: An Expanding Therapeutic Opportunity in Gastrointestinal Cancers","volume":"12","author":"Graham","year":"2023","journal-title":"Chin. Clin. Oncol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1038\/s41573-024-00896-6","article-title":"The Present and Future of Bispecific Antibodies for Cancer Therapy","volume":"23","author":"Klein","year":"2024","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1007\/s40265-025-02163-3","article-title":"Zanidatamab: First Approval","volume":"85","author":"Keam","year":"2025","journal-title":"Drugs"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1038\/35052073","article-title":"Untangling the ErbB Signalling Network","volume":"2","author":"Yarden","year":"2001","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.1038\/s41467-023-37029-3","article-title":"An anti-HER2 biparatopic antibody that induces unique HER2 clustering and complement-dependent cytotoxicity","volume":"14","author":"Weisser","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"3838","DOI":"10.1002\/cncr.30254","article-title":"Biliary Cancer: Utility of Next-Generation Sequencing for Clinical Management","volume":"122","author":"Javle","year":"2016","journal-title":"Cancer"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"6094","DOI":"10.1158\/1078-0432.CCR-17-0899","article-title":"Real-Time Genomic Profiling of Pancreatic Ductal Adenocarcinoma: Potential Actionability and Correlation with Clinical Phenotype","volume":"23","author":"Lowery","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"2153410","DOI":"10.1080\/19420862.2022.2153410","article-title":"Antibodies to watch in 2023","volume":"15","author":"Kaplon","year":"2023","journal-title":"mAbs"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"2443538","DOI":"10.1080\/19420862.2024.2443538","article-title":"Antibodies to watch in 2025","volume":"17","author":"Crescioli","year":"2025","journal-title":"mAbs"},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Shan, K.S., Musleh Ud Din, S., Dalal, S., Gonzalez, T., Dalal, M., Ferraro, P., Hussein, A., and Vulfovich, M. (2025). Bispecific antibodies in solid tumors: Advances and challenges. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26125838"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1038\/nrc1609","article-title":"ERBB Receptors and Cancer: The Complexity of Targeted Inhibitors","volume":"5","author":"Hynes","year":"2005","journal-title":"Nat. Rev. Cancer"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/nrc2656","article-title":"Novel Anticancer Targets: Revisiting ERBB2 and Discovering ERBB3","volume":"9","author":"Baselga","year":"2009","journal-title":"Nat. Rev. Cancer"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1038\/s41467-023-36399-y","article-title":"Antitumour Activity of Neratinib in Patients with HER2-Mutant Advanced Biliary Tract Cancers","volume":"14","author":"Harding","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"E11","DOI":"10.1038\/s41586-019-0974-0","article-title":"Author Correction: HER Kinase Inhibition in Patients with HER2- and HER3-Mutant Cancers","volume":"566","author":"Hyman","year":"2019","journal-title":"Nature"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1016\/S2468-1253(21)00171-0","article-title":"Current and emerging therapies for advanced biliary tract cancers","volume":"6","author":"Kam","year":"2021","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1007\/s40487-025-00370-2","article-title":"Opportunities and approaches to optimising advanced cholangiocarcinoma outcomes in the era of targeted therapies: A narrative review","volume":"13","author":"Macarulla","year":"2025","journal-title":"Oncol. Ther."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s40364-024-00565-1","article-title":"HER2-Targeted Therapies in Cancer: A Systematic Review","volume":"12","author":"Zhu","year":"2024","journal-title":"Biomark. Res."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1007\/s00280-022-04471-x","article-title":"Population pharmacokinetics of zanidatamab, an anti-HER2 biparatopic antibody, in patients with advanced or metastatic cancer","volume":"90","author":"Proctor","year":"2022","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_160","doi-asserted-by":"crossref","unstructured":"Kanwal, W., Narjis, K., Musani, S., Nancy, F., Qureshi, L., Mudasir, M., Naseem, R., Tooba, F., Yousuf, J., and Farhan, K. (2025). Exploring Zanidatamab\u2019s Efficacy across HER2-Positive Malignancies: A Narrative Review. BMC Cancer, 25.","DOI":"10.1186\/s12885-025-13749-1"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"2319","DOI":"10.1080\/14796694.2024.2368952","article-title":"A Plain Language Summary of the Results from the Phase 2b HERIZON-BTC-01 Study of Zanidatamab in Participants with HER2-Amplified Biliary Tract Cancer","volume":"20","author":"Harding","year":"2024","journal-title":"Future Oncol."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1001\/jamaoncol.2025.4736","article-title":"Zanidatamab in HER2-Positive Metastatic Biliary Tract Cancer: Final Results from HERIZON-BTC-01","volume":"12","author":"Pant","year":"2026","journal-title":"JAMA Oncol."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"115432","DOI":"10.1016\/j.ejca.2025.115432","article-title":"Real-World Efficacy of Zanidatamab in Patients with HER2-Positive Advanced Biliary Tract Cancers","volume":"222","author":"Smolenschi","year":"2025","journal-title":"Eur. J. Cancer"},{"key":"ref_164","doi-asserted-by":"crossref","unstructured":"(2025). Zanidatamab (Ziihera) for biliary tract cancer. Med. Lett. Drugs Ther., 67, e16\u2013e17.","DOI":"10.58347\/tml.2025.1720f"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"1416","DOI":"10.1111\/bph.17458","article-title":"Novel drugs approved by the EMA, the FDA and the MHRA in 2024: A year in review","volume":"182","author":"Topouzis","year":"2025","journal-title":"Br. J. Pharmacol."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"3290","DOI":"10.1002\/cncr.29471","article-title":"Second-Line Chemotherapy for Advanced Biliary Tract Cancer after Failure of the Gemcitabine-Platinum Combination: A Large Multicenter Study by the Association des Gastro-Ent\u00e9rologues Oncologues","volume":"121","author":"Brieau","year":"2015","journal-title":"Cancer"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"155","DOI":"10.17998\/jlc.2024.08.07","article-title":"New Systemic Treatment Options for Advanced CCA","volume":"24","author":"Zanuso","year":"2024","journal-title":"J. Liver Cancer"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"104655","DOI":"10.1016\/j.critrevonc.2025.104655","article-title":"HER2-Targeted Therapies: Unraveling Their Role in Biliary Tract Cancers","volume":"208","author":"Theocharopoulos","year":"2025","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"4125","DOI":"10.1007\/s12325-024-02975-x","article-title":"Efficacy of Trastuzumab Deruxtecan in HER2-Expressing Solid Tumors by Enrollment HER2 IHC Status: Post Hoc Analysis of DESTINY-PanTumor02","volume":"41","author":"Oaknin","year":"2024","journal-title":"Adv. Ther."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1097\/CCO.0000000000001043","article-title":"State of the art and upcoming trends in HER2-directed therapies in gastrointestinal malignancies","volume":"36","author":"Lee","year":"2024","journal-title":"Curr. Opin. Oncol."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"107695","DOI":"10.1016\/j.bioorg.2024.107695","article-title":"Advances in HER2-targeted therapies: From monoclonal antibodies to dual inhibitors developments in cancer treatment","volume":"151","author":"Bhagyalalitha","year":"2024","journal-title":"Bioorganic Chem."},{"key":"ref_172","doi-asserted-by":"crossref","unstructured":"Rogers, J.E., and Ajani, J.A. (2026). Bispecific antibodies and antibody-drug conjugates in advanced gastric adenocarcinoma. Cancers, 18.","DOI":"10.3390\/cancers18091448"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1016\/j.annonc.2020.07.014","article-title":"Recommendations for the Use of Next-Generation Sequencing (NGS) for Patients with Metastatic Cancers: A Report from the ESMO Precision Medicine Working Group","volume":"31","author":"Mosele","year":"2020","journal-title":"Ann. Oncol."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1007\/s11523-025-01132-w","article-title":"HER2 Pathway in Biliary Tract Cancer: A Snapshot of the Current Understanding and Future Directions","volume":"20","author":"Camera","year":"2025","journal-title":"Target. Oncol."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1080\/14712598.2025.2556903","article-title":"An Evaluation of Zanidatamab, a Novel, Anti-HER2 Biparatopic Antibody, for the Treatment of Biliary Tract Cancer","volume":"25","author":"Yoon","year":"2025","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"S237","DOI":"10.1016\/j.annonc.2024.08.2078","article-title":"TiP HERIZON-BTC-302: A Phase III Study of Zanidatamab with Standard-of-Care (SOC) Therapy vs SOC Alone for First-Line (1L) Treatment of Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Advanced\/Metastatic Biliary Tract Cancer (BTC)","volume":"35","author":"Harding","year":"2024","journal-title":"Ann. Oncol."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"3255","DOI":"10.2217\/fon-2022-0595","article-title":"HERIZON-GEA-01: Zanidatamab + chemo tislelizumab for 1L treatment of HER2-positive gastroesophageal adenocarcinoma","volume":"18","author":"Tabernero","year":"2022","journal-title":"Future Oncol."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"4293","DOI":"10.1038\/s41467-025-59279-z","article-title":"Zanidatamab monotherapy or combined with chemotherapy in HER2-expressing gastroesophageal adenocarcinoma: A phase 1 trial","volume":"16","author":"Rha","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"2002","DOI":"10.1056\/NEJMoa2517729","article-title":"Zanidatamab with and without tislelizumab in HER2-positive gastroesophageal cancer","volume":"394","author":"Shitara","year":"2026","journal-title":"N. Engl. J. Med."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"593457","DOI":"10.2147\/OTT.S593457","article-title":"Research on Targeted Therapy for Malignant Tumors of the Biliary Tract","volume":"19","author":"Yang","year":"2026","journal-title":"OncoTargets Ther."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"oyaf258","DOI":"10.1093\/oncolo\/oyaf258","article-title":"HER2 Alterations across Solid Tumors: Implications for Comprehensive Testing","volume":"30","author":"Ismail","year":"2025","journal-title":"Oncologist"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"1758835919833519","DOI":"10.1177\/1758835919833519","article-title":"HER2-Positive Breast Cancer: New Therapeutic Frontiers and Overcoming Resistance","volume":"11","author":"Pernas","year":"2019","journal-title":"Ther. Adv. Med. Oncol."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1158\/2159-8290.CD-17-1260","article-title":"Targeted Therapies for Targeted Populations: Anti-EGFR Treatment for EGFR-Amplified Gastroesophageal Adenocarcinoma","volume":"8","author":"Maron","year":"2018","journal-title":"Cancer Discov."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"e2400594","DOI":"10.1200\/PO-24-00594","article-title":"Safety and Efficacy of Anti-Human Epidermal Growth Factor 2 Agents in the Treatment of Biliary Tract Cancers: A Systematic Review","volume":"9","author":"Naleid","year":"2025","journal-title":"JCO Precis. Oncol."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1158\/2159-8290.CD-23-0838","article-title":"Co-clinical trial of novel bispecific anti-HER2 antibody zanidatamab in patient-derived xenografts","volume":"14","author":"DiPeri","year":"2024","journal-title":"Cancer Discov."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.humpath.2020.08.006","article-title":"Details of Human Epidermal Growth Factor Receptor 2 Status in 454 Cases of Biliary Tract Cancer","volume":"105","author":"Hiraoka","year":"2020","journal-title":"Hum. Pathol."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1158\/1078-0432.CCR-25-4464","article-title":"Shaping the Future of HER2-Directed Therapy in Biliary Tract Cancer","volume":"32","author":"Fitzpatrick","year":"2026","journal-title":"Clin. Cancer Res."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1038\/nrcardio.2015.65","article-title":"Cardiotoxicity of Anticancer Treatments","volume":"12","author":"Ewer","year":"2015","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.ygyno.2023.12.028","article-title":"A phase 2 trial of zanidatamab in HER2-overexpressed advanced endometrial carcinoma and carcinosarcoma (ZW25-IST-2)","volume":"182","author":"Lumish","year":"2024","journal-title":"Gynecol. Oncol."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1016\/S1470-2045(25)00140-8","article-title":"Zanidatamab plus palbociclib and fulvestrant in previously treated patients with hormone receptor-positive, HER2-positive metastatic breast cancer: Primary results from a two-part, multicentre, single-arm, phase 2a study","volume":"26","author":"Cejalvo","year":"2025","journal-title":"Lancet Oncol."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"105852","DOI":"10.1016\/j.esmoop.2025.105852","article-title":"Zanidatamab in combination with docetaxel in first-line HER2-positive breast cancer: Results from an open-label, multicenter, phase Ib\/II study","volume":"10","author":"Wang","year":"2025","journal-title":"ESMO Open"},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1158\/1078-0432.CCR-24-4295","article-title":"Phase Ib\/II study of zanidatamab in combination with tislelizumab and chemotherapy in first-line HER2-positive gastric\/gastroesophageal junction adenocarcinoma","volume":"32","author":"Lee","year":"2026","journal-title":"Clin. Cancer Res."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1016\/j.annonc.2024.04.005","article-title":"Recommendations for the Use of Next-Generation Sequencing (NGS) for Patients with Advanced Cancer in 2024: A Report from the ESMO Precision Medicine Working Group","volume":"35","author":"Mosele","year":"2024","journal-title":"Ann. Oncol."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1016\/S1470-2045(25)00287-6","article-title":"Zanidatamab plus Chemotherapy as First-Line Treatment for Patients with HER2-Positive Advanced Gastro-Oesophageal Adenocarcinoma: Primary Results of a Multicentre, Single-Arm, Phase 2 Study","volume":"26","author":"Elimova","year":"2025","journal-title":"Lancet Oncol."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"2136","DOI":"10.1158\/1078-0432.CCR-25-4158","article-title":"Zanidatamab, a dual HER2-targeted bispecific antibody, in patients with unresectable locally advanced or metastatic HER2-positive salivary gland cancer: A combined analysis of early-phase studies","volume":"32","author":"Lee","year":"2026","journal-title":"Clin. Cancer Res."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1038\/s41571-025-01048-4","article-title":"Zanidatamab shows promise as first-line therapy for advanced-stage HER2(+) GEA","volume":"22","author":"Killock","year":"2025","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1016\/S1470-2045(25)00301-8","article-title":"Zanidatamab, a bispecific monoclonal antibody for HER2-positive gastro-oesophageal adenocarcinoma patients: A new hope?","volume":"26","author":"Coutzac","year":"2025","journal-title":"Lancet Oncol."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1038\/s41571-026-01169-4","article-title":"First-line zanidatamab-chemotherapy with or without tislelizumab improves survival in advanced-stage HER2(+) GEA","volume":"23","author":"Romero","year":"2026","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"102245","DOI":"10.1016\/j.clinre.2023.102245","article-title":"New developments and standard of care in the management of advanced gastric cancer","volume":"48","author":"Depotte","year":"2024","journal-title":"Clin. Res. Hepatol. Gastroenterol."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"11","DOI":"10.3892\/mi.2026.295","article-title":"Multimodal treatment and tumour biology-driven long-term survival in PSC-associated hilar cholangiocarcinoma: A case report","volume":"6","author":"Florou","year":"2026","journal-title":"Med. Int."},{"key":"ref_201","unstructured":"(2026, August 09). Ziihera\u00ae (Zanidatamab-hrii) Prescribing Information. U.S. Food and Drug Administration, Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2024\/761416s000lbl.pdf."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.ccr.2010.01.020","article-title":"The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate","volume":"17","author":"Ward","year":"2010","journal-title":"Cancer Cell"},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1101\/gad.217406.113","article-title":"What a difference a hydroxyl makes: Mutant IDH, (R)-2-hydroxyglutarate, and cancer","volume":"27","author":"Losman","year":"2013","journal-title":"Genes Dev."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1158\/2159-8290.CD-13-0083","article-title":"Oncogenic isocitrate dehydrogenase mutations: Mechanisms, models, and clinical opportunities","volume":"3","author":"Cairns","year":"2013","journal-title":"Cancer Discov."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1634\/theoncologist.2011-0386","article-title":"Frequent mutation of isocitrate dehydrogenase (IDH)1 and IDH2 in CCA identified through broad-based tumor genotyping","volume":"17","author":"Borger","year":"2012","journal-title":"Oncologist"},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.1038\/ng.2813","article-title":"Exome sequencing identifies frequent inactivating mutations in BAP1, ARID1A and PBRM1 in intrahepatic CCAs","volume":"45","author":"Jiao","year":"2013","journal-title":"Nat. Genet."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1038\/nature13441","article-title":"Mutant IDH inhibits HNF-4\u03b1 to block hepatocyte differentiation and promote biliary cancer","volume":"513","author":"Saha","year":"2014","journal-title":"Nature"},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1007\/s40265-018-0978-3","article-title":"Ivosidenib: First global approval","volume":"78","author":"Dhillon","year":"2018","journal-title":"Drugs"},{"key":"ref_209","doi-asserted-by":"crossref","unstructured":"Ivanov, S., Nano, O., Hana, C., Bonano-Rios, A., and Hussein, A. (2024). Molecular targeting of the isocitrate dehydrogenase pathway and the implications for cancer therapy. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25137337"},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.ejcsup.2025.12.001","article-title":"Clinical advancement in the management of mutant isocitrate dehydrogenase (IDH) cancers","volume":"17","author":"Bridgewater","year":"2026","journal-title":"EJC Suppl."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"20420986251347376","DOI":"10.1177\/20420986251347376","article-title":"Safety profiles of the new target therapies\u2014Pemigatinib, futibatinib, and ivosidenib\u2014For the treatment of CCA: A systematic review","volume":"16","author":"Matranga","year":"2025","journal-title":"Ther. Adv. Drug Saf."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"e370","DOI":"10.1016\/S1470-2045(20)30343-0","article-title":"Ivosidenib for advanced IDH1-mutant CCA","volume":"21","author":"Gervaso","year":"2020","journal-title":"Lancet Oncol."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1007\/s11523-023-01002-3","article-title":"Ivosidenib: A review in advanced CCA","volume":"18","author":"Frampton","year":"2023","journal-title":"Target. Oncol."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1080\/17474124.2021.1915765","article-title":"Ivosidenib for the treatment of isocitrate dehydrogenase-1 mutant cholangiocarcinoma","volume":"15","author":"Corrigan","year":"2021","journal-title":"Expert Rev. Gastroenterol. Hepatol."},{"key":"ref_215","first-page":"e21018","article-title":"Ivosidenib for IDH1 mutant cholangiocarcinoma: A narrative review","volume":"14","author":"Sumbly","year":"2022","journal-title":"Cureus"},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.1080\/14656566.2022.2138331","article-title":"An evaluation of ivosidenib for the treatment of IDH1-mutant cholangiocarcinoma","volume":"23","author":"Tella","year":"2022","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1007\/s11523-024-01106-4","article-title":"Correction: Ivosidenib: A review in advanced cholangiocarcinoma","volume":"20","author":"Frampton","year":"2025","journal-title":"Target. Oncol."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"100159","DOI":"10.1016\/j.esmogo.2025.100159","article-title":"Quantitative benefit-risk assessment of data from the phase III ClarIDHy study of ivosidenib versus placebo in patients with mIDH1 CCA","volume":"8","author":"Valle","year":"2025","journal-title":"ESMO Gastrointest. Oncol."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"e371","DOI":"10.1016\/S1470-2045(20)30394-6","article-title":"Ivosidenib for advanced IDH1-mutant cholangiocarcinoma\u2014Authors\u2019 reply","volume":"21","author":"Pandya","year":"2020","journal-title":"Lancet Oncol."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.2147\/CMAR.S326060","article-title":"Clinical utility of ivosidenib in the treatment of IDH1-mutant cholangiocarcinoma: Evidence to date","volume":"15","author":"Borad","year":"2023","journal-title":"Cancer Manag. Res."},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1097\/CAD.0000000000001757","article-title":"Safety and efficacy of ivosidenib in the treatment of isocitrate dehydrogenase 1 mutant cholangiocarcinoma and acute myeloid leukemia: A systematic review and meta-analysis","volume":"36","author":"Qasim","year":"2025","journal-title":"Anticancer Drugs"},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1080\/14796694.2025.2470609","article-title":"IDHIRA: A prospective, observational study on ivosidenib in patients with IDH1 R132-mutated advanced CCA","volume":"21","author":"Michl","year":"2025","journal-title":"Future Oncol."},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.ctrv.2018.09.002","article-title":"Biliary tract cancer: State of the art and potential role of DNA damage repair","volume":"70","author":"Lamarca","year":"2018","journal-title":"Cancer Treat. Rev."},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.cld.2020.04.005","article-title":"CCA: Diagnosis and management","volume":"24","author":"Buckholz","year":"2020","journal-title":"Clin. Liver Dis."},{"key":"ref_225","doi-asserted-by":"crossref","unstructured":"(2026). Ivosidenib for cholangiocarcinoma and acute myeloid leukaemia. Aust. Prescr., 49, 36\u201338.","DOI":"10.18773\/austprescr.2026.004"},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"108170","DOI":"10.1016\/j.pharmthera.2022.108170","article-title":"Ivosidenib in IDH1-mutated CCA: Clinical evaluation and future directions","volume":"237","author":"Lavacchi","year":"2022","journal-title":"Pharmacol. Ther."},{"key":"ref_227","doi-asserted-by":"crossref","unstructured":"Chen, K.A., Huang, W.M., Chen, E.Y., Ho, P.K., Chueh, C.H., Wen, Y.W., Chen, M.H., Chiang, N.J., and Tsai, Y.W. (2024). Cost-effectiveness of ivosidenib versus chemotherapy for previously treated IDH1-mutant advanced intrahepatic cholangiocarcinoma in Taiwan. BMC Cancer, 24.","DOI":"10.1186\/s12885-024-12362-y"},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/j.hbpd.2025.12.018","article-title":"Cost-effectiveness of ivosidenib in patients with previously treated isocitrate dehydrogenase 1 (IDH1)-mutant cholangiocarcinoma: An Italian perspective","volume":"25","author":"Giuliani","year":"2026","journal-title":"Hepatobiliary Pancreat. Dis. Int."},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"S103","DOI":"10.1016\/j.annonc.2025.05.277","article-title":"Preliminary efficacy outcomes of ivosidenib in patients with IDH1-mutated CCA (mIDH1 CCA): Initial results from the phase IIIb ProvIDHe study","volume":"36","author":"Bridgewater","year":"2025","journal-title":"Ann. Oncol."},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"e70295","DOI":"10.1111\/liv.70295","article-title":"Ivosidenib for IDH1-mutant intrahepatic CCA: Insights from a multicenter real-world study","volume":"45","author":"Niger","year":"2025","journal-title":"Liver Int."},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"2733","DOI":"10.1158\/1078-0432.CCR-21-4462","article-title":"FDA approval summary: Ivosidenib for the treatment of patients with advanced unresectable or metastatic, chemotherapy refractory CCA with an IDH1 mutation","volume":"28","author":"Casak","year":"2022","journal-title":"Clin. Cancer Res."},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"17588359231171574","DOI":"10.1177\/17588359231171574","article-title":"Updated survival outcomes with ivosidenib in patients with previously treated IDH1-mutated intrahepatic cholangiocarcinoma: An Italian real-world experience","volume":"15","author":"Rimini","year":"2023","journal-title":"Ther. Adv. Med. Oncol."},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"4280","DOI":"10.1158\/1078-0432.CCR-20-0834","article-title":"Differentiation syndrome with ivosidenib and enasidenib treatment in patients with relapsed or refractory IDH-mutated AML: A U.S. Food and Drug Administration systematic analysis","volume":"26","author":"Norsworthy","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"1894","DOI":"10.1182\/bloodadvances.2020001503","article-title":"Molecular mechanisms mediating relapse following ivosidenib monotherapy in IDH1-mutant relapsed or refractory AML","volume":"4","author":"Choe","year":"2020","journal-title":"Blood Adv."},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1158\/2159-8290.CD-18-0877","article-title":"Isoform switching as a mechanism of acquired resistance to mutant isocitrate dehydrogenase inhibition","volume":"8","author":"Harding","year":"2018","journal-title":"Cancer Discov."},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1038\/s41586-018-0251-7","article-title":"Acquired resistance to IDH inhibition through trans or cis dimer-interface mutations","volume":"559","author":"Intlekofer","year":"2018","journal-title":"Nature"},{"key":"ref_237","doi-asserted-by":"crossref","unstructured":"Zhuang, X., Pei, H.Z., Li, T., Huang, J., Guo, Y., Zhao, Y., Yang, M., Zhang, D., Chang, Z., and Zhang, Q. (2022). The molecular mechanisms of resistance to IDH inhibitors in acute myeloid leukemia. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.931462"},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1038\/s41698-022-00304-5","article-title":"Secondary IDH1 resistance mutations and oncogenic IDH2 mutations cause acquired resistance to ivosidenib in cholangiocarcinoma","volume":"6","author":"Cleary","year":"2022","journal-title":"npj Precis. Oncol."},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1182\/blood-2017-04-779405","article-title":"Enasidenib in Mutant IDH2 Relapsed or Refractory Acute Myeloid Leukemia","volume":"130","author":"Stein","year":"2017","journal-title":"Blood"},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1097\/HEP.0000000000001185","article-title":"Tumor-Derived CCL2 Drives Tumor Growth and Immunosuppression in IDH1-Mutant Cholangiocarcinoma","volume":"82","author":"Zabransky","year":"2025","journal-title":"Hepatology"},{"key":"ref_241","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1158\/1078-0432.CCR-25-3284","article-title":"MAPK pathway mutations emerge in mutant IDH1 inhibitor-resistant cholangiocarcinoma and attenuate the IFN response","volume":"32","author":"Wan","year":"2026","journal-title":"Clin. Cancer Res."},{"key":"ref_242","doi-asserted-by":"crossref","first-page":"2403334","DOI":"10.1080\/20450923.2024.2403334","article-title":"Integration of circulating tumor DNA in biliary tract cancer: The emerging landscape","volume":"11","author":"Awosika","year":"2024","journal-title":"Hepatic Oncol."},{"key":"ref_243","doi-asserted-by":"crossref","first-page":"3668","DOI":"10.1007\/s12094-026-04334-4","article-title":"Circulating tumor DNA-based detection of molecular residual disease in isocitrate dehydrogenase-mutant cholangiocarcinoma for biomarker-guided therapy","volume":"28","author":"Yumashev","year":"2026","journal-title":"Clin. Transl. Oncol."},{"key":"ref_244","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1038\/s41591-018-0095-6","article-title":"Suppression of antitumor T cell immunity by the oncometabolite (R)-2-hydroxyglutarate","volume":"24","author":"Bunse","year":"2018","journal-title":"Nat. Med."},{"key":"ref_245","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1002\/hep.32424","article-title":"Biology of IDH mutant CCA","volume":"75","author":"Wu","year":"2022","journal-title":"Hepatology"},{"key":"ref_246","doi-asserted-by":"crossref","first-page":"e00909","DOI":"10.1097\/HC9.0000000000000909","article-title":"Mitochondrial targets in IDH1-mutated cholangiocarcinoma","volume":"10","author":"Carvalho","year":"2026","journal-title":"Hepatol. Commun."},{"key":"ref_247","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1158\/2767-9764.CRC-25-0591","article-title":"Mutant isocitrate dehydrogenase 1 sensitizes intrahepatic cholangiocarcinoma cells to MDM2 inhibitors","volume":"6","author":"Liu","year":"2026","journal-title":"Cancer Res. Commun."},{"key":"ref_248","doi-asserted-by":"crossref","first-page":"101899","DOI":"10.1016\/j.jhepr.2026.101899","article-title":"IDH1 R132 mutations or HER2-positivity and benefit from platinum-based therapy for biliary tract cancers","volume":"8","author":"Tesini","year":"2026","journal-title":"JHEP Rep."},{"key":"ref_249","doi-asserted-by":"crossref","unstructured":"Darman, L., Kaurich, Q., Hassan, M.S., von Holzen, U., and Awasthi, N. (2025). Expanding horizons in cholangiocarcinoma: Emerging targets beyond FGFR2 and IDH1. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms262110755"},{"key":"ref_250","doi-asserted-by":"crossref","first-page":"347","DOI":"10.35772\/ghm.2025.01102","article-title":"Perioperative and precision strategies in resectable intrahepatic cholangiocarcinoma","volume":"7","author":"Chen","year":"2025","journal-title":"Glob. Health Med."},{"key":"ref_251","first-page":"1107","article-title":"State of the art of IDH inhibitors: Emerging questions and perspectives","volume":"26","author":"Lima","year":"2026","journal-title":"Anticancer Agents Med. Chem."},{"key":"ref_252","doi-asserted-by":"crossref","first-page":"e199730","DOI":"10.1172\/JCI199730","article-title":"The allosteric IDH1 inhibitor ivosidenib overcomes chemoresistance in intrahepatic cholangiocarcinoma models expressing wild-type IDH1","volume":"136","author":"Li","year":"2026","journal-title":"J. Clin. Investig."},{"key":"ref_253","unstructured":"(2026, August 09). Tibsovo\u00ae (Ivosidenib) Prescribing Information. U.S. Food and Drug Administration, Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2018\/211192s000lbl.pdf."},{"key":"ref_254","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1007\/s11523-026-01211-6","article-title":"Real-world outcomes of ivosidenib in IDH1-mutant biliary tract cancer: A multicenter retrospective analysis and comparison with the TriNetX database","volume":"21","author":"Dreikhausen","year":"2026","journal-title":"Target. Oncol."},{"key":"ref_255","doi-asserted-by":"crossref","first-page":"100262","DOI":"10.1016\/j.esmogo.2025.100262","article-title":"Real-world treatment patterns and outcomes in biliary tract cancer: A Danish retrospective cohort study","volume":"10","author":"Markussen","year":"2025","journal-title":"ESMO Gastrointest. Oncol."},{"key":"ref_256","doi-asserted-by":"crossref","first-page":"2625","DOI":"10.1080\/14796694.2024.2379237","article-title":"Real-world treatment patterns, resource utilization and costs in biliary tract cancers in the USA","volume":"20","author":"Wang","year":"2024","journal-title":"Future Oncol."},{"key":"ref_257","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1007\/s11523-023-01000-5","article-title":"A systematised literature review of real-world treatment patterns and outcomes in unresectable advanced or metastatic biliary tract cancer","volume":"18","author":"Peirce","year":"2023","journal-title":"Target. Oncol."},{"key":"ref_258","doi-asserted-by":"crossref","first-page":"112056","DOI":"10.1016\/j.ejrad.2025.112056","article-title":"Molecular Signatures of Intrahepatic Cholangiocarcinoma: Role in Targeted Therapy Selection","volume":"187","author":"Glushko","year":"2025","journal-title":"Eur. J. Radiol."},{"key":"ref_259","doi-asserted-by":"crossref","first-page":"217540","DOI":"10.1016\/j.canlet.2025.217540","article-title":"Current Status and Prospects of Targeted Therapy for Cholangiocarcinoma Based on Molecular Characteristics","volume":"614","author":"Cui","year":"2025","journal-title":"Cancer Lett."},{"key":"ref_260","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1016\/S1470-2045(20)30157-1","article-title":"Ivosidenib in IDH1-mutant, chemotherapy-refractory CCA (ClarIDHy): A multicentre, randomised, double-blind, placebo-controlled, phase 3 study","volume":"21","author":"Macarulla","year":"2020","journal-title":"Lancet Oncol."},{"key":"ref_261","doi-asserted-by":"crossref","unstructured":"Chen, W., Hu, Z., Song, J., Wu, Y., Zhang, B., and Zhang, L. (2022). The state of therapy modalities in clinic for biliary tract cancer. Front. Biosci., 27.","DOI":"10.31083\/j.fbl2706185"},{"key":"ref_262","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.bpg.2015.02.010","article-title":"Future Directions in the Treatment of Cholangiocarcinoma","volume":"29","author":"Zhu","year":"2015","journal-title":"Best Pract. Res. Clin. Gastroenterol."},{"key":"ref_263","doi-asserted-by":"crossref","first-page":"2738","DOI":"10.2174\/0113816128428934260307141948","article-title":"Cholangiocarcinoma in the Era of Precision Medicine: Emerging Insights and Therapeutic Strategies","volume":"32","author":"Agarwal","year":"2026","journal-title":"Curr. Pharm. Des."},{"key":"ref_264","doi-asserted-by":"crossref","first-page":"e70230","DOI":"10.1111\/apm.70230","article-title":"Predictive Immunohistochemistry in Cholangiocarcinoma: Current Clinical Utility, Practical Limitations, and Emerging Directions","volume":"134","author":"Vasuri","year":"2026","journal-title":"APMIS"},{"key":"ref_265","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1200\/JCO.2017.76.8671","article-title":"Circulating tumor DNA analysis in patients with cancer: American Society of Clinical Oncology and College of American Pathologists Joint Review","volume":"36","author":"Merker","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_266","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1080\/14737159.2026.2670701","article-title":"Liquid Biopsy for Biliary Tract Cancer: Available Evidence and Future Research Directions","volume":"26","author":"Erul","year":"2026","journal-title":"Expert Rev. Mol. Diagn."},{"key":"ref_267","doi-asserted-by":"crossref","first-page":"113564","DOI":"10.1016\/j.ejca.2024.113564","article-title":"Revolutionizing anti-HER2 therapies for extrahepatic CCA and gallbladder cancer: Current advancements and future perspectives","volume":"199","author":"Pedregal","year":"2024","journal-title":"Eur. J. Cancer"},{"key":"ref_268","doi-asserted-by":"crossref","first-page":"e000279","DOI":"10.1136\/esmoopen-2017-000279","article-title":"Activating HER2 mutations as emerging targets in multiple solid cancers","volume":"2","author":"Connell","year":"2017","journal-title":"ESMO Open"},{"key":"ref_269","doi-asserted-by":"crossref","unstructured":"Kawczak, P., Feszak, I.J., and B\u0105czek, T. (2025). Targeted Therapies Modulating Mesenchymal\u2013Epithelial Transition-Linked Oncogenic Signaling in the Tumor Microenvironment: Comparative Profiling of Capmatinib, Bemcentinib, and Galunisertib. J. Clin. Med., 14.","DOI":"10.3390\/jcm14196853"},{"key":"ref_270","doi-asserted-by":"crossref","first-page":"1833","DOI":"10.1080\/14656566.2023.2259802","article-title":"FGFR Inhibitor Resistance in Cholangiocarcinoma: Current Understanding and Future Directions","volume":"24","author":"Neureiter","year":"2023","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_271","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1159\/000545308","article-title":"Anti-human epidermal growth factor receptor-2 therapies in biliary tract cancers: A meta-analysis on disease location, human epidermal growth factor receptor-2 status, and survival outcomes","volume":"104","author":"Camera","year":"2026","journal-title":"Oncology"},{"key":"ref_272","doi-asserted-by":"crossref","first-page":"e19386","DOI":"10.7717\/peerj.19386","article-title":"Comparative Efficacy of Targeted Therapy, Chemotherapy and Their Combination for Advanced Cholangiocarcinoma: A Systematic Review and Network Meta-Analysis","volume":"13","author":"Liao","year":"2025","journal-title":"PeerJ"},{"key":"ref_273","doi-asserted-by":"crossref","unstructured":"Du, J., Lv, X., Zhang, Z., Huang, Z., and Zhang, E. (2023). Revisiting targeted therapy and immunotherapy for advanced CCA. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1142690"},{"key":"ref_274","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1097\/CM9.0000000000002759","article-title":"Advances in immunotherapy for biliary tract cancers","volume":"137","author":"Zhao","year":"2024","journal-title":"Chin. Med. J."},{"key":"ref_275","doi-asserted-by":"crossref","unstructured":"Rossari, F., Sala, M., Rimini, M., Camera, S., Persano, M., Tonon, G., Bonini, C., Cangi, M.G., Pecciarini, L., and Doglioni, C. (2026). Proof-of-Principle 4-Marker Spatial Profiling Reveals Distinct, Location-Independent Immune Clusters in Biliary Tract Cancers. Pathol. Oncol. Res., 32.","DOI":"10.3389\/pore.2026.1612389"},{"key":"ref_276","doi-asserted-by":"crossref","first-page":"101850","DOI":"10.1016\/j.jhepr.2026.101850","article-title":"Role of the Stromal and Immune Microenvironment in Intrahepatic Cholangiocarcinoma","volume":"8","author":"Affo","year":"2026","journal-title":"JHEP Rep."},{"key":"ref_277","first-page":"581943","article-title":"Cancer-Associated Fibroblasts in the Treatment of Intrahepatic Cholangiocarcinoma: Present and Prospects","volume":"13","author":"Yuan","year":"2026","journal-title":"J. Hepatocell. Carcinoma"},{"key":"ref_278","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/s41591-018-0316-z","article-title":"A guide to deep learning in healthcare","volume":"25","author":"Esteva","year":"2019","journal-title":"Nat. Med."},{"key":"ref_279","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/s41591-018-0300-7","article-title":"High-performance medicine: The convergence of human and artificial intelligence","volume":"25","author":"Topol","year":"2019","journal-title":"Nat. Med."},{"key":"ref_280","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1038\/nature15819","article-title":"Patient-centric trials for therapeutic development in precision oncology","volume":"526","author":"Biankin","year":"2015","journal-title":"Nature"},{"key":"ref_281","doi-asserted-by":"crossref","unstructured":"Cossiga, V., Guarino, M., Capasso, M., and Morisco, F. (2023). Relevance of Bile Acids in Cholangiocarcinoma Pathogenesis: Critical Revision and Future Directions. Cells, 12.","DOI":"10.3390\/cells12121576"},{"key":"ref_282","doi-asserted-by":"crossref","unstructured":"Ike, I., Teymouri, F., Crook, C., Guzman, S., Hazeltine, M., Castillo, D., Li, D., and Brar, G. (2026). The Interplay between Bile Acid Metabolism and Gut Microbiome in Biliary Tract Cancers. Front. Microbiomes, 5.","DOI":"10.3389\/frmbi.2026.1774429"},{"key":"ref_283","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1186\/s13062-026-00861-w","article-title":"Analysis and Validation of Abnormal Signaling Pathways and Immune Cell Infiltration Characteristics in Digestive System Cancers Based on Peroxisome-Related Genes","volume":"21","author":"Wen","year":"2026","journal-title":"Biol. Direct"},{"key":"ref_284","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1007\/s11523-023-00998-y","article-title":"Trastuzumab deruxtecan: A review in gastric or gastro-oesophageal junction adenocarcinoma","volume":"18","author":"Kang","year":"2023","journal-title":"Target. Oncol."},{"key":"ref_285","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S1470-2045(21)00605-7","article-title":"Sotorasib for previously treated colorectal cancers with KRASG12C mutation (CodeBreaK100): A prespecified analysis of a single-arm, phase 2 trial","volume":"23","author":"Fakih","year":"2022","journal-title":"Lancet Oncol."},{"key":"ref_286","doi-asserted-by":"crossref","unstructured":"Khanna, V., Vadde, S., Henry, A.S., Johnson, T.P., Shaheen, S., Heestand, G.M., Holden, T., Chong, C.R., Goyal, L., and Fisher, G.A. (2026). Clinical Benefit of Various HER2-Directed Regimens in Gastrointestinal Malignancies: A Retrospective Cohort Study. BMC Cancer, 26.","DOI":"10.1186\/s12885-026-16309-3"},{"key":"ref_287","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1056\/NEJMra1706169","article-title":"Chimeric antigen receptor therapy","volume":"379","author":"June","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_288","doi-asserted-by":"crossref","unstructured":"Saccu, G., and Fagoonee, S. (2026). Lipid Nanoparticles and Extracellular Vesicles: Emerging Cell Free Therapeutic Platforms for Hepatobiliary Cancers. Front. Cell Dev. Biol., 14.","DOI":"10.3389\/fcell.2026.1812373"},{"key":"ref_289","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1056\/NEJMp1405158","article-title":"Updating cost-effectiveness\u2014The curious resilience of the $50,000-per-QALY threshold","volume":"371","author":"Neumann","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_290","doi-asserted-by":"crossref","first-page":"e72060","DOI":"10.1002\/hsr2.72060","article-title":"The economic burden of gastric cancer: A systematic review","volume":"9","author":"Bordbar","year":"2026","journal-title":"Health Sci. Rep."},{"key":"ref_291","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s10549-013-2666-z","article-title":"The impact of the Oncotype Dx breast cancer assay in clinical practice: A systematic review and meta-analysis","volume":"141","author":"Carlson","year":"2013","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_292","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1007\/s10198-019-01032-7","article-title":"Is rate of return pricing a useful approach when value-based pricing is not appropriate?","volume":"20","author":"Drummond","year":"2019","journal-title":"Eur. J. Health Econ."},{"key":"ref_293","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1056\/NEJMra1510062","article-title":"Master protocols to study multiple therapies, multiple diseases, or both","volume":"377","author":"Woodcock","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_294","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1200\/JCO.2014.59.8433","article-title":"Basket trials and the evolution of clinical trial design in an era of genomic medicine","volume":"33","author":"Redig","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_295","doi-asserted-by":"crossref","unstructured":"Chen, Q.F., Hu, Y., Chen, S., Jiang, X.Y., and Zhao, M. (2026). Hepatic Artery Infusion Chemotherapy for Cholangiocarcinoma in 2025. Liver Cancer, Online ahead of print.","DOI":"10.1159\/000551430"},{"key":"ref_296","doi-asserted-by":"crossref","first-page":"222","DOI":"10.4103\/jcrt.jcrt_707_25","article-title":"Advancements in Selective Internal Radiotherapy: Efficacy, Safety, and Future Directions","volume":"22","author":"Zhang","year":"2026","journal-title":"J. Cancer Res. Ther."},{"key":"ref_297","doi-asserted-by":"crossref","first-page":"100378","DOI":"10.1016\/j.esmoop.2021.100378","article-title":"How I treat biliary tract cancer","volume":"7","author":"Lamarca","year":"2022","journal-title":"ESMO Open"},{"key":"ref_298","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/S1470-2045(18)30915-X","article-title":"Capecitabine compared with observation in resected biliary tract cancer (BILCAP): A randomised, controlled, multicentre, phase 3 study","volume":"20","author":"Primrose","year":"2019","journal-title":"Lancet Oncol."},{"key":"ref_299","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1016\/S1470-2045(20)30321-1","article-title":"Dabrafenib plus trametinib in patients with BRAFV600E-mutated biliary tract cancer (ROAR): A phase 2, open-label, single-arm, multicentre basket trial","volume":"21","author":"Subbiah","year":"2020","journal-title":"Lancet Oncol."},{"key":"ref_300","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1056\/NEJMoa1714448","article-title":"Efficacy of larotrectinib in TRK fusion-positive cancers in adults and children","volume":"378","author":"Drilon","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_301","doi-asserted-by":"crossref","first-page":"104923","DOI":"10.1016\/j.critrevonc.2025.104923","article-title":"Is it a new era for intrahepatic CCA?","volume":"215","author":"Liguori","year":"2025","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_302","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1016\/j.ejso.2020.03.202","article-title":"Outcomes in older patients with biliary tract cancer","volume":"47","author":"McNamara","year":"2021","journal-title":"Eur. J. Surg. Oncol."},{"key":"ref_303","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1080\/0284186X.2017.1418532","article-title":"Translating the ABC-02 trial into daily practice: Outcome of palliative treatment in patients with unresectable biliary tract cancer treated with gemcitabine and cisplatin","volume":"57","author":"Dierks","year":"2018","journal-title":"Acta Oncol."},{"key":"ref_304","doi-asserted-by":"crossref","first-page":"791","DOI":"10.4143\/crt.2017.044","article-title":"Chemotherapy versus best supportive care in advanced biliary tract carcinoma: A multi-institutional propensity score matching analysis","volume":"50","author":"Ji","year":"2018","journal-title":"Cancer Res. Treat."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/19\/7396\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T12:51:50Z","timestamp":1790167910000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/19\/7396"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,23]]},"references-count":304,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2026,10]]}},"alternative-id":["jcm15197396"],"URL":"https:\/\/doi.org\/10.3390\/jcm15197396","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,23]]}}}