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7 "Targeted therapy"
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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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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
  • 4,503 Views
  • 237 Downloads
  • 4 Citations
AbstractAbstract 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.

Citations

Citations to this article as recorded by  
  • 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;[Epub]     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
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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.

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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
  • 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
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
  • 687 Views
  • 2 Downloads
AbstractAbstract 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.
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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
  • 654 Views
  • 0 Download
AbstractAbstract 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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