Journal of Liver Cancer

Review Articles

Epidemiology and genomic features of biliary tract cancer and its unique features in Korea: Seonjeong Woo, Youngun Kim, Sohyun Hwang, Hong Jae Chon; J Liver Cancer. 2025;25(1):41-51. Published online March 4, 2025; DOI: https://doi.org/10.17998/jlc.2025.02.27

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Biliary tract cancer (BTC) is a rare but highly aggressive malignancy that includes intrahepatic cholangiocarcinoma (ICC), extrahepatic cholangiocarcinoma, and gallbladder cancer (GBC). While BTC has a low global incidence, its regional variations are notable. Among nations, Korea has the second-highest incidence of BTC globally, with the highest mortality rate worldwide, underscoring the need for a deeper understanding of this cancer. Liver fluke infection and hepatitis B virus infection are key risk factors unique to Korea, contributing to regional differences in BTC incidence. Additionally, genomic alterations in Korean patients with BTC differ from those in other populations, including lower frequencies of IDH1 mutations and FGFR2 fusions in ICC and a higher prevalence of ERBB2 amplification in GBC. Recognizing the clinical significance of these alterations, ivosidenib and pemigatinib have been approved in Korea for BTC patients with IDH1 mutations and FGFR2 fusions, respectively. This review explores the epidemiology, risk factors, and molecular features of BTC, along with corresponding targeted therapies. Furthermore, we compare the unique characteristics of BTC in Korea with global data to inform future research and clinical practice.

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Global, regional, and national burden of gallbladder and biliary tract cancer among adults aged 55 years and older, 2010–2021
Mingjuan Li, Jiaguang Li, Shuangjiang Li, Minmin Zhang, Shuang Li, Jiahui Zhao, Tao Gan, Min Wu, Shunwen Luo, Yunying Liang, Qiuyun Li, Guangdong Pan, Jianqing Yang, Guoqing Ouyang
Frontiers in Nutrition.2025;[Epub] CrossRef
Changing patterns of cholangiocarcinoma and gallbladder cancer: A regional perspective from Northeastern Italy
Duygu Kirkik, Ayse Naz Ozabaci, Sevgi Kalkanli Tas
World Journal of Gastrointestinal Oncology.2025;[Epub] CrossRef

Molecular and immune landscape of hepatocellular carcinoma for therapeutic development: Hiroyuki Suzuki, Sumit Mishra, Subhojit Paul, Yujin Hoshida; J Liver Cancer. 2025;25(1):9-18. Published online December 6, 2024; DOI: https://doi.org/10.17998/jlc.2024.12.02

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Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, with an estimated 750,000 deaths in 2022. Recent emergence of molecular targeted agents and immune checkpoint inhibitors and their combination therapies have been transforming HCC care, but their prognostic impact in advanced-stage disease remains unsatisfactory. In addition, their application to early-stage disease is still an unmet need. Omics profiling studies have elucidated recurrent and heterogeneously present molecular aberrations involved in pro-cancer tumor (immune) microenvironment that may guide therapeutic strategies. Recurrent aberrations such somatic mutations in TERT promoter and TP53 have been regarded undruggable, but recent studies have suggested that these may serve as new classes of therapeutic targets. HCC markers such as alpha-fetoprotein, glypican-3, and epithelial cell adhesion molecule have also been explored as therapeutic targets. These molecular features may be utilized as biomarkers to guide the application of new approaches as companion biomarkers to maximize therapeutic benefits in patients who are likely to benefit from the therapies, while minimizing unnecessary harm in patients who will not respond. The explosive number of new agents in the pipelines have posed challenges in their clinical testing. Novel clinical trial designs guided by predictive biomarkers have been proposed to enable their efficient and cost-effective evaluation. These new developments collectively facilitate clinical translation of personalized molecular-targeted therapies in HCC and substantially improve prognosis of HCC patients.

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Paracancerous binuclear hepatocytes assessed by computer program is a novel biomarker for short term recurrence of hepatocellular carcinoma after surgery
Yifan Zhang, Yiquan Lu, Nan Wang, Fengjie Hao, Yongjun Chen, Xiaochun Fei, Junqing Wang
Scientific Reports.2025;[Epub] CrossRef
Differential Infiltration of T-Cell Populations in Tumor and Liver Tissues Predicts Recurrence-Free Survival in Surgically Resected Hepatocellular Carcinoma
Eun Ji Jang, Ho Joong Choi, Young Kyoung You, Deok Hwa Seo, Mi Hyun Kwon, Keungmo Yang, Jaejun Lee, Jeong Won Jang, Seung Kew Yoon, Ji Won Han, Pil Soo Sung
Cancers.2025; 17(9): 1548. CrossRef
Decision-Making Biomarkers Guiding Therapeutic Strategies in Hepatocellular Carcinoma: From Prediction to Personalized Care
Dongming Liu, Norihiro Imai
Cancers.2025; 17(19): 3105. CrossRef
YKL-40 in Virus-Associated Liver Disease: A Translational Biomarker Linking Fibrosis, Hepatocarcinogenesis, and Liver Transplantation
Jadranka Pavicic Saric, Dinka Lulic, Dunja Rogic, Stipislav Jadrijevic, Danko Mikulic, Tajana Filipec Kanizaj, Nikola Prpic, Laura Karla Bozic, Ivona Adamovic, Iva Bacak Kocman, Zrinka Sarec, Gorjana Erceg, Mirta Adanic, Petra Ozegovic Zuljan, Filip Jadri
International Journal of Molecular Sciences.2025; 26(19): 9584. CrossRef

New systemic treatment options for advanced cholangiocarcinoma: Valentina Zanuso, Giulia Tesini, Elena Valenzi, Lorenza Rimassa; J Liver Cancer. 2024;24(2):155-170. Published online August 8, 2024; DOI: https://doi.org/10.17998/jlc.2024.08.07

30,630 Views
565 Downloads
13 Citations

Abstract PDF

Cholangiocarcinoma (CCA) is a rare and aggressive cancer, mostly diagnosed at advanced or metastatic stage, at which point systemic treatment represents the only therapeutic option. Chemotherapy has been the backbone of advanced CCA treatment. More recently, immunotherapy has changed the therapeutic landscape, as immune checkpoint inhibitors have yielded the first improvement in survival and currently, the addition of either durvalumab or pembrolizumab to standard of care cisplatin plus gemcitabine represents the new first-line treatment option. However, the use of immunotherapy in subsequent lines has not demonstrated its efficacy and therefore, it is not approved, except for pembrolizumab in the selected microsatellite instability-high population. In addition, advances in comprehensive genomic profiling have led to the identification of targetable genetic alterations, such as isocitrate dehydrogenase 1 (IDH1), fibroblast growth factor receptor 2 (FGFR2), human epidermal growth factor receptor 2 (HER2), proto-oncogene B-Raf (BRAF), neurotrophic tropomyosin receptor kinase (NTRK), rearranged during transfection (RET), Kirsten rat sarcoma virus (KRAS), and mouse double minute 2 homolog (MDM2), thus favoring the development of a precision medicine approach in previously treated patients. Despite these advances, the use of molecularly driven agents is limited to a subgroup of patients. This review aims to provide an overview of the newly approved systemic therapies, the ongoing studies, and future research challenges in advanced CCA management.

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Genomic and transcriptomic signatures of sequential carcinogenesis from papillary neoplasm to biliary tract cancer
Taek Chung, Seungho Oh, Jeongsoo Won, Jiho Park, Jeong Eun Yoo, Ho Kyoung Hwang, Gi Hong Choi, Chang Moo Kang, Dai Hoon Han, Sangwoo Kim, Young Nyun Park
Journal of Hepatology.2025; 83(1): 119. CrossRef
A concise review of updated global guidelines for the management of hepatocellular carcinoma: 2017-2024
Hyunjae Shin, Su Jong Yu
Journal of Liver Cancer.2025; 25(1): 19. CrossRef
Modulating Wnt/β-catenin pathway activity to enhance chemosensitivity in cholangiocarcinoma
Kevin Delgado-Calvo, Luke Boulter, Oscar Briz, Aleksandra Rozyczko, Paula Olaizola, Jose J.G. Marin, Rocio I.R. Macias, Elisa Lozano
Biomedicine & Pharmacotherapy.2025; 188: 118225. CrossRef
Regorafenib plus modified gemcitabine-oxaliplatin in patients with advanced biliary tract cancer. The randomized phase Ib/II BREGO study
Jean-Frédéric Blanc, Mohamed Bouattour, Ludovic Gauthier, Emmanuel Deshayes, Sophie Guillemard, Yann Touchefeu, Fabienne Portales, Christophe Borg, Lobna Harguem, Rosine Guimbaud, Laurent Mineur, Marc Ychou, Thibault Mazard, Eric Assenat
The Oncologist.2025;[Epub] CrossRef
The new era of cholangiocarcinoma treatment: application of nano-based drug delivery systems
Paweena Dana, Prattana Tanyapanyachon, Saksorn Klibaim, Monthira Rattanatayarom, Walailuk Chonniyom, Nattika Saengkrit
Hepatoma Research.2025;[Epub] CrossRef
Diagnostic value of quantitative DWI and IVIM parameters in differentiating intrahepatic cholangiocarcinoma and hepatocellular carcinoma: a systematic review and meta-analysis
Saeed Mohammadzadeh, Alisa Mohebbi, Mehrad Zare, Faeze Salahshour, Afshin Mohammadi
Abdominal Radiology.2025;[Epub] CrossRef
Advanced cholangiocarcinoma with human epidermal growth factor receptor 2 (HER2) amplification treated with Trastuzumab deruxtecan (T-DXd): A case report
Xiaohui Bao, Zhi Chen, Jin Xiong, Zhenzhou Yang, Ni Zhang
Medicine.2025; 104(35): e44094. CrossRef
Validation of prognostic models for predicting postsurgical outcomes in intrahepatic cholangiocarcinoma patients using a multicenter cohort
Dong Hwan Kim, Sang Hyun Choi, Sehee Kim, Woohyung Lee, Hyung-Don Kim, Hyungjin Rhee, Eun-Suk Cho, Suk-Keu Yeom, Sumi Park, Seung Soo Lee, Mi-Suk Park
International Journal of Surgery.2025; 111(10): 7032. CrossRef
The Antibody–Drug Conjugate Sacituzumab Govitecan (IMMU-132) Represents a Potential Novel Therapeutic Strategy in Cholangiocarcinoma
Racha Hosni, Niklas Klümper, Christine Sanders, Sana Hosni, Vittorio Branchi, Alexander Semaan, Abdullah Alajati, Natalie Pelusi, Susanna S. Ng, Damian J. Ralser, Saif-Eldin Abedellatif, Hanno Matthaei, Jörg Kalff, Jasmitha Boovadira Poonacha, Veronika Lu
Molecular Cancer Therapeutics.2025; 24(11): 1775. CrossRef
Molecular Mechanisms and Therapeutic Perspectives of Gut Microbiota, Autophagy, and Apoptosis in Cholangiocarcinoma Pathophysiology
Viviana A. Ruiz-Pozo, Santiago Cadena-Ullauri, Patricia Guevara-Ramírez, Rafael Tamayo-Trujillo, Elius Paz-Cruz, Alejandro Cabrera-Andrade, Ana Karina Zambrano
International Journal of Molecular Sciences.2025; 26(20): 9949. CrossRef
Is 26S proteasome non-ATPase regulatory subunit 6 a potential molecular target for intrahepatic cholangiocarcinoma?
Yong-Zhi Zhuang, Li-Quan Tong, Xue-Ying Sun
World Journal of Hepatology.2024; 16(11): 1219. CrossRef
Imaging findings of intrahepatic cholangiocarcinoma for prognosis prediction and treatment decision-making: a narrative review
Jun Gu Kang, Taek Chung, Dong Kyu Kim, Hyungjin Rhee
The Ewha Medical Journal.2024;[Epub] CrossRef
Resectability and survival outcome in real world practice of 720 cholangiocarcinoma patients: intrahepatic, perihilar and distal cholangiocarcinoma.
Poowanai Sarkhampee, Weeris Ouransatien, Nithi Lertsawatvicha, Satsawat Chansitthichock, Paiwan Wattanarath
World Journal of Surgical Oncology.2024;[Epub] CrossRef

Systemic therapy for advanced hepatocellular carcinoma: consideration for selecting second-line treatment: Bo Hyun Kim, Joong-Won Park; J Liver Cancer. 2021;21(2):124-138. Published online September 30, 2021; DOI: https://doi.org/10.17998/jlc.2021.09.23

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4 Citations

Abstract PDF

Several molecular-targeted agents have been tested as first- or second-line therapies for hepatocellular carcinoma (HCC) but failed to improve clinical outcomes; sorafenib has been the only approved systemic agent for treating HCC for almost 10 years. Regorafenib resulted in a significant improvement in overall survival and thus was approved for HCC patients previously treated with sorafenib. Subsequently, cabozantinib and ramucirumab demonstrated superior overall survival compared with placebos in phase III clinical trials. Immune checkpoint inhibitors such as nivolumab with or without ipilimumab and pembrolizumab are also available in some countries for patients who are unresponsive to sorafenib. Some second-line agents are available for patients who are unresponsive to sorafenib; however, little is known about the considerations for selecting appropriate secondline systemic agents. Hence, this study aimed to review the current and future perspectives of second-line systemic agents.

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Exploring the efficacy of fluorouracil and platinum based chemotherapy in advanced hepatocellular carcinoma to bridge the treatment gap in resource limited settings
Se Jun Park, Kabsoo Shin, In-Ho Kim, MyungAh Lee, Tae Ho Hong, Hyunho Kim
Scientific Reports.2025;[Epub] CrossRef
Effect of regorafenib combined with immunotherapy and arterial chemoembolization on the survival of patients with advanced hepatocellular carcinoma: a retrospective study
Mingqiang Liu
American Journal of Translational Research.2025; 17(3): 1962. CrossRef
Expression of Peptidyl Arginine Deiminase 2 Is Closely Associated with Recurrence in Patients with Hepatocellular Carcinoma
Sunho Uhm, Yoon Cho, Ji-Young Choe, Ji Park, Min-Jeong Kim, Won-Ho Han, Junyong Lee, Jung Lee, Dong Shin, Jae Soh, Hyun Lim, Ho Kang, Sung-Hoon Moon, Sung-Eun Kim
Diagnostics.2023; 13(4): 659. CrossRef
Expert consensus on the management of adverse events in patients receiving lenvatinib for hepatocellular carcinoma
Bo Hyun Kim, Su Jong Yu, Wonseok Kang, Sung Bum Cho, Soo Young Park, Seung Up Kim, Do Young Kim
Journal of Gastroenterology and Hepatology.2022; 37(3): 428. CrossRef

Systemic Therapy for Advanced Hepatocellular Carcinoma: Targeted Therapy and Immunotherapy: Kim, Bo Hyun , Park, Joong Won; J Liver Cancer. 2018;18(1):17-22. Published online March 31, 2018; DOI: https://doi.org/10.17998/jlc.18.1.17

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81 Downloads
2 Citations

Abstract PDF

Systemic therapy for hepatocellular carcinoma (HCC) has markedly changed since 2007, with the approval of sorafenib. Sorafenib improved the overall survival of patients with advanced HCC; however, the modest efficacy and toxicity of this therapy present unmet needs. Subsequently, a variety of molecular targeted agents have been tested as first-line or secondline therapies but have failed, and sorafenib has remained the only approved systemic agent for almost 10 years. Recently, regorafenib significantly improved overall survival and was approved for patients with HCC who have been previously treated with sorafenib. Nivolumab, a programmed death protein-1 inhibitor, was also approved as second-line therapy, based on remarkable response rates.

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Sequential Use of Sorafenib and Regorafenib in Hepatocellular Cancer Recurrence After Liver Transplantation: Treatment Strategies and Outcomes
Mehmet Fatih Ozbay, Hakan Harputluoglu, Mustafa Karaca, Omer Tekin, Mehmet Ali Nahit Şendur, Muhammed Ali Kaplan, Berksoy Sahin, Caglayan Geredeli, Fatih Teker, Deniz Tural, Sezer Saglam, Timuçin Çil, Ahmet Bilici, Cihan Erol, Ziya Kalkan, Ertugrul Bayram
Cancers.2024; 16(22): 3880. CrossRef
Analysis of Existing Guidelines and Randomized, Controlled, Clinical Trials for Development of [Guideline of Clinical Trial on Herbal Medicinal Product for Liver Cancer]
Ga-jin Han, Dong-hun Kim, Eun-joo Park, Sin Seong, Sung-su Kim, Jung-tae Leem
The Journal of Internal Korean Medicine.2019; 40(1): 89. CrossRef

Case Report

A Case of Management for Hepatocellular Carcinoma with Lung Metastasis: Han Jo Jeon, Tae Hyung Kim, Soon Ho Um, Yeon Seok Seo, Hyun Seo Kim, Ki Joon Lim, Seung Woon Park, Han Ah Lee, Dong-Sik Kim; J Liver Cancer. 2016;16(2):129-133. Published online September 30, 2016; DOI: https://doi.org/10.17998/jlc.16.2.129

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Abstract PDF: Liver cancer is the 2nd most common cause of cancer related death in Korea. Especially, patients who present extrahepatic spread of hepatocellular carcinoma (HCC) have a shorter life expectancy (50% survival at 1 year and less than 4 months of median overall survival). Molecular target agent like sorafenib was usually mentioned as a treatment for them, but that was still not firmly established. We present a 75 year-old who had expanding nodular type of HCC. The mass was removed by resection and radiofrequency ablation. However, lung metastasis were revealed shortly after surgery. That lesions were treated with lenvatinib and systemic chemotherapy.

Review Articles

New Treatment Response Evaluation Criteria and Current Therapeutics for Hepatocellular Carcinoma: Hyung Joon Yim; Journal of the Korean Liver Cancer Study Group. 2009;9(1):17-23. Published online June 30, 2009

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Abstract PDF: There has been no proven effective therapy in the setting of advanced HCC (hepatocellular carcinoma) according to BCLC (Barcelona Clinic Liver Cancer). Targeted therapy opened a new era in this subset of patients. Although sorafenib showed survival benefit, objective tumor response is uncommon, while systemic chemotherapies sometimes show partial tumor response without statistically significant survival benefits. These findings suggest evaluation of treatment response should not depend on conventional treatment response evaluation criteria. Overall survival is now considered to be the most important endpoint and time to disease progression can be secondary endpoint. Time to recurrence is the primary endpoint after the curative therapy. Currently, targeted therapy in addition to known curative or palliative therapy is now under investigation for synergistic effects, and new therapeutic agents are under development. Such advancement in the treatment of HCC will certainly have a great impact on patients’ survival in the near future.

New Targeted Agents for Hepatocellular Carcinoma: Joong-Won Park; Journal of the Korean Liver Cancer Study Group. 2008;8(1):16-17. Published online June 30, 2008

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Abstract PDF: Most patients with hepatocellular carcinoma (HCC) present with advanced stage tumors at the time of initial diagnosis, only about 30%, who present with early stage tumors, undergo radical therapies such as resection, liver transplantation, and percutaneous ablation. Thus, over 50% of HCC patients receive palliative treatments. The newly developed, molecularly targeted agents, sorafenib is the first agent that has shown significant survival benefits for European and American patients with advanced HCC and sets the new standard for the first-line treatment of these patients. The role of sorafenib and other promising agents should be examined in the adjuvant setting after RFA, TACE, surgical resection or selective settings in liver transplantation in an attempt to improve further the outcomes of these patients.

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