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Conventional markers such as CA19-9 and CEA show inadequate diagnostic accuracy. Molecular genetics has revealed actionable alterations that support targeted therapies and can improve outcomes. Liquid biopsies using cfDNA and ctDNA enable non-invasive, real-time monitoring of tumor dynamics, heterogeneity, and treatment response. Non-coding RNAs in serum and bile may further aid diagnosis and prognosis, while immune checkpoint inhibitors work in subsets and require tumor immune microenvironment profiling.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/biomarkers-and-management-of-cholangiocarcinoma-unveiling-new-horizons-for-precision-therapy/507514/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/biomarkers-and-management-of-cholangiocarcinoma-unveiling-new-horizons-for-precision-therapy/507514.png","ImageObject",300,407,{"name":92,"@type":93},"Ophelia","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-28","2026-10-05",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",12,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"Why are reliable biomarkers needed for cholangiocarcinoma (CCA)?","Question",{"text":113,"@type":114},"CCA has limited early detection methods and lacks effective screening for high-risk populations. Reliable biomarkers are needed to improve diagnosis and guide management.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"What are conventional tumor markers, and what limitation do they have?",{"text":118,"@type":114},"Conventional tumor markers such as CA19-9 and CEA are used clinically, but they show insufficient diagnostic accuracy for CCA.",{"name":120,"@type":111,"acceptedAnswer":121},"How do liquid biopsies and non-coding RNAs contribute to CCA management?",{"text":122,"@type":114},"Liquid biopsies using cfDNA and ctDNA provide non-invasive, real-time monitoring of tumor dynamics, heterogeneity, and treatment response. Non-coding RNAs in serum and bile are also highlighted as promising diagnostic and prognostic biomarkers.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},507514,1791345390,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":26,"preview_page_count":4},7971461741311,"https://ap-avatar.wpscdn.com/avatar/74000253aff267980c6?x-image-process=image/resize,m_fixed,w_180,h_180&k=1779345379180704826","Review  \nBiomarkers and Management of Cholangiocarcinoma: Unveiling New Horizons for Precision Therapy  \nNaoshi Nishida   \nAcademic Editor: Takahiro Kodama  \nReceived: 22 January 2025  \nRevised: 31 March 2025  \nAccepted: 3 April 2025  \nPublished: 6 April 2025  \nCitation: Nishida, N. Biomarkers and Management of Cholangiocarcinoma: Unveiling New Horizons for Precision Therapy. Cancers 2025, 17, 1243 . [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)cancers17071243  \nCopyright: © 2025 by the author. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://creativecommons.org/](https://creativecommons.org/)[ ](https://creativecommons.org/)[licenses/by/4.0/](licenses/by/4.0/)) .  \nDepartment of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University Osaka 589-8511, Japan; [naoshi@med.kindai.ac.jp](naoshi@med.kindai.ac.jp); Tel.: +81-72-366-0221  \nSimple Summary: This review aims to provide a comprehensive update on the development of biomarker and therapeutic agents in cholangiocarcinoma (CCA) . CCA is an aggressive malignancy with limited early detection methods, necessitating reliable biomarkers for diagnosis and management. Conventional tumor markers lack diagnostic accuracy; recent advancements in next-generation sequencing have identified actionable mutations, such as FGFR2 fusions and IDH1/2 mutations, enabling targeted therapies that improve survival. Cancer panels facilitating multiplex profiling reveal actionable mutations, with mutation-guided therapies markedly enhancing outcomes. Liquid biopsies, including cfDNA and ctDNA, offer non-invasive, real-time tumor monitoring. Non-coding RNAsin serum and bile also show promise as diagnostic and prognostic biomarkers. Immune checkpoint inhibitors (ICIs) demonstrate efficacy in subsets of patients; analyses of tumor immune microenvironment (TME) may also provide valuable information. Integrating multi-omics approaches and advanced technologies holds the potential to revolutionize precision medicine, enabling early detection, improved prognosis, and personalized therapies in CCA.  \nAbstract: Cholangiocarcinoma (CCA) is an aggressive malignancy with limited methods for early detection, necessitating the development of reliable biomarkers for diagnosis and management. However, conventional tumor markers, such as CA19-9 and CEA, exhibit insufficient diagnostic accuracy. Recent advancements in molecular genetics have identified several actionable mutations in CCA, enabling molecularly targeted therapies that improve survival in patients harboring these genetic alterations. Cancer panels, which facilitate multiplex genetic profiling, are critical for identifying these mutations. Studies indicate that several actionable mutations are detected in CCA cases, with patients receiving mutationguided therapies achieving markedly better outcomes. Liquid biopsies, including cell-free DNA and circulating tumor DNA, offer real-time, non-invasive approaches to monitoring tumor dynamics, heterogeneity, and treatment responses. Furthermore, numerous studies have identified non-coding RNAs in serum and bile as promising biomarkers for the diagnosis and management of CCA. On the other hand, immunotherapy, particularly immune checkpoint inhibitors, has shown efficacy in subsets of CCA patients. However, the success of these therapies is often affected by the status of the tumor immune microenvironment (TME), underscoring the need for comprehensive TME analysis to predict responses to immune checkpoint inhibitors. Despite these advances, no single biomarker currently demonstrates sufficient sensitivity or specificity for clinical application. The integration of multi-omics approaches with cutting-edge technologies holds promise for enhancing diagnostic accuracy, optimizing treatment stratification, and advancing precision medicine in","cbCaiidPmas3d9Cw","https://ap.wps.com/l/cbCaiidPmas3d9Cw","pdf",2328875,24,"English","# Introduction\n## Systemic Therapy and Rationale for Biomarkers\n# Abstract and Core Themes\n## Molecularly Targeted Therapies\n## Liquid Biopsies and Non-coding RNAs\n## Immunotherapy and Tumor Immune Microenvironment\n# Keywords","[{\"question\":\"Why are reliable biomarkers needed for cholangiocarcinoma (CCA)?\",\"answer\":\"CCA has limited early detection methods and lacks effective screening for high-risk populations. Reliable biomarkers are needed to improve diagnosis and guide management.\"},{\"question\":\"What are conventional tumor markers, and what limitation do they have?\",\"answer\":\"Conventional tumor markers such as CA19-9 and CEA are used clinically, but they show insufficient diagnostic accuracy for CCA.\"},{\"question\":\"How do liquid biopsies and non-coding RNAs contribute to CCA management?\",\"answer\":\"Liquid biopsies using cfDNA and ctDNA provide non-invasive, real-time monitoring of tumor dynamics, heterogeneity, and treatment response. Non-coding RNAs in serum and bile are also highlighted as promising diagnostic and prognostic biomarkers.\"}]","Biomarkers and Management of Cholangiocarcinoma: Unveiling New Horizons for Precision Therapy | PDF",1791180020]