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Review Articles
Molecular and immune landscape of hepatocellular carcinoma for therapeutic development
Hiroyuki Suzuki, Sumit Mishra, Subhojit Paul, Yujin Hoshida
Received October 30, 2024  Accepted December 2, 2024  Published online December 6, 2024  
DOI: https://doi.org/10.17998/jlc.2024.12.02    [Accepted]
  • 788 Views
  • 140 Downloads
AbstractAbstract PDF
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 (MTAs) and immune checkpoint inhibitors (ICIs) 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 (AFP), glypican-3 (GPC3), and epithelial cell adhesion molecule (EpCAM) 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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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
  • 5,150 Views
  • 127 Downloads
  • 3 Citations
AbstractAbstract 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.

Citations

Citations to this article as recorded by  
  • 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
  • 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
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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
  • 2,664 Views
  • 80 Downloads
  • 2 Citations
AbstractAbstract 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.

Citations

Citations to this article as recorded by  
  • 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
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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
  • 1,356 Views
  • 18 Downloads
AbstractAbstract 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.
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Review Articles
Systemic Therapy in Advanced Hepatocellular Carcinoma
Hye Jin Choi
Journal of the Korean Liver Cancer Study Group. 2011;11(1):33-39.   Published online February 28, 2011
  • 668 Views
  • 1 Download
AbstractAbstract PDF
Understanding the mechanism of hepatocarcinogenesis has provided the opportunity to evaluate the efficacy of molecularly targeted agents in HCC. Sorafenib is a multikinase inhibitor with antiangiogenic, proapoptotic, and Raf kinase inhibitory effects, and it is the first new agent to consistently prolong overall survival in patients with advanced hepatocellular carcinoma (HCC). The success of sorafenib is a milestone for systemic therapy of HCC, shifting the paradigm of systemic treatment to molecular targeted agents. Many novel agents that inhibit angiogenesis, epidermal growth factor receptor, and mammalian target of rapamycin are under clinical development. This review attempts to summarize the current status and future perspectives of systemic therapy in HCC.
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Prediction of Tumor Biology in Hepatocellular Carcinoma
Won Kim
Journal of the Korean Liver Cancer Study Group. 2009;9(1):1-6.   Published online June 30, 2009
  • 715 Views
  • 4 Downloads
AbstractAbstract PDF
Hepatocellular carcinoma (HCC) surveillance programs have led to an increase in the adoption of radical therapies. Nevertheless, HCCs often present at an advanced stage and the prognosis remains dismal even after resection due to the high rate of recurrence. The study of tumor biology is important to predict clinical outcome enabling more appropriate therapeutic decisions for HCC patients. Understanding molecular mechanisms of hepatocarcinogenesis may also lead to effective strategies in chemoprevention. However, current staging systems based on clinicopathologic factors are limited in prognostic prediction. Recently, there has been great interest in the study of gene expression profile in relation to prognosis of HCC. Global gene expression profiling may be the most appropriate technology to unravel the pathogenesis of HCC and explore its heterogeneous origin. The elucidation of tumor biology of HCC is of paramount clinical importance in the new era of molecular target therapy.
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