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Cancers
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Molecular Markers and Targeted Therapy for Hepatobiliary Tumors
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Molecular Markers and Targeted Therapy for Hepatobiliary Tumors

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: 15 December 2025 | Viewed by 13034

Special Issue Editor

Dr. Masaki Kuwatani

E-Mail Website
Guest Editor
Department of Gastroenterology and Hepatology, Hokkaido University Hospital, Hokkaido, Japan
Interests: photoimmunotherapy; endoscopy; biliary tract cancer; pancreatic cancer; pancreatitis; acute pancreatitis model; mesenchymal stem cells

Special Issue Information

Dear Colleagues,

The poor prognoses of hepatobiliary malignancies such as cholangiocarcinoma and hepatocellular carcinoma, with 5-year relative survival rates of about 20%, are attributed to their difficult early detection and fewer curative, less-invasive anticancer therapies. Recently, some molecular markers for them have been reported, using new technologies such as liquid biopsy, organoids, exosome isolation, and single cell analysis. Based on these, several targeted therapies have also been reported in preclinical and clinical settings. Furthermore, appropriate molecular markers for assessing the efficacy of anti-cancer therapies are also required in order to maximize and manage therapies and improve the prognosis.

This Special Issue aims to publish research related to cutting-edge/preclinical molecular markers for diagnosis or treatment assessment and targeted therapies for hepatobiliary malignancies. Consequently, the development of future research leading to improvements of clinical outcomes is anticipated.

We are pleased to invite you to submit articles on the above-mentioned topics. In this Special Issue, original research articles and reviews are welcome. Research areas may include the following: molecular biology; pathology; genetics; organoids; exosome; chemotherapy; and phototherapy.

I look forward to receiving your contributions.

Dr. Masaki Kuwatani
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • cholangiocarcinoma
  • hepatocellular carcinoma
  • molecule
  • gene
  • chemotherapy
  • phototherapy

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Published Papers (6 papers)

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Research

Jump to: Review

14 pages, 1671 KiB  
Article
Utility of Transpapillary Biopsy and Endoscopic Ultrasound-Guided Tissue Acquisition for Comprehensive Genome Profiling of Unresectable Biliary Tract Cancer
by Soma Fukuda, Susumu Hijioka, Yoshikuni Nagashio, Daiki Yamashige, Daiki Agarie, Yuya Hagiwara, Kohei Okamoto, Shin Yagi, Yasuhiro Komori, Masaru Kuwada, Yuta Maruki, Chigusa Morizane, Hideki Ueno, Nobuyoshi Hiraoka, Kiichiro Tsuchiya and Takuji Okusaka
Cancers 2024, 16(16), 2819; https://doi.org/10.3390/cancers16162819 - 10 Aug 2024
Viewed by 1618
Abstract
Tissue sampling in biliary tract cancer (BTC) is generally performed through transpapillary biopsy (TPB) or endoscopic ultrasound-guided tissue acquisition (EUS-TA). For the first time, we compared the suitability of specimens obtained using TPB and EUS-TA to determine the optimal tissue-sampling method for comprehensive [...] Read more.
Tissue sampling in biliary tract cancer (BTC) is generally performed through transpapillary biopsy (TPB) or endoscopic ultrasound-guided tissue acquisition (EUS-TA). For the first time, we compared the suitability of specimens obtained using TPB and EUS-TA to determine the optimal tissue-sampling method for comprehensive genome profiling (CGP) analysis in patients with unresectable BTC (UR-BTC). Pathology precheck criteria for CGP analysis comprised the OncoGuide NCC Oncopanel System (NCCOP) and FoundationOne CDx (F1CDx). Seventy-eight patients with UR-BTC (35 TPB and 43 EUS-TA) were included. The NCCOP analysis suitability achievement rate was higher in EUS-TA specimens than in TPB specimens (34.9% vs. 8.6%, p = 0.007), whereas that of F1CDx was 0% in both groups. EUS-TA was identified as an independent factor that contributed to the suitability of the NCCOP analysis. The suitability of the NCCOP analysis of EUS-TA specimens showed a tendency to be higher for mass lesions (43.8% vs. 9.1%, p = 0.065), especially for target size ≥ 18.5 mm, and lower for perihilar cholangiocarcinoma (0% vs. 41.7%, p = 0.077). In TPB, papillary-type lesions (66.7% vs. 3.2%, p = 0.016) and peroral cholangioscopy-assisted biopsies (50.0% vs. 3.3%, p = 0.029) showed better potential for successful NCCOP analysis. EUS-TA is suitable for NCCOP analysis in UR-BTC and may be partially complemented by TPB. Full article
(This article belongs to the Special Issue Molecular Markers and Targeted Therapy for Hepatobiliary Tumors)
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Review

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31 pages, 2278 KiB  
Review
Astrocyte Elevated Gene-1/Metadherin (AEG-1/MTDH): A Promising Molecular Marker and Therapeutic Target for Hepatocellular Carcinoma
by Eva Davis, Ali Gawi Ermi and Devanand Sarkar
Cancers 2025, 17(8), 1375; https://doi.org/10.3390/cancers17081375 - 21 Apr 2025
Viewed by 334
Abstract
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths. The 5-year survival rate has been estimated to be less than 20% while its incidence rates have more than tripled since the 1980s. Astrocyte elevated gene-1/Metadherin (AEG-1/MTDH) has been demonstrated to [...] Read more.
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths. The 5-year survival rate has been estimated to be less than 20% while its incidence rates have more than tripled since the 1980s. Astrocyte elevated gene-1/Metadherin (AEG-1/MTDH) has been demonstrated to have an influential role in HCC progression and the development of an aggressive phenotype. AEG-1 has been shown to be upregulated in many cancers, including HCC. Studies have shown that it plays a crucial role in the proliferation, invasion and metastasis, and evasion of apoptosis in HCC. Its relationship with proteins and pathways, such as MYC, SND1, PI3K/AKT, and other signaling pathways demonstrates its pertinent role in oncogenic development and relevance as a biomarker and therapeutic target. Recent studies have shown that AEG-1 is present in tumor tissues, and the anti-AEG-1 antibody is detected in the blood of cancer patients, demonstrating its viability as a diagnostic/prognostic marker. This review paper shines light on recent findings regarding the molecular implications of AEG-1, with emphasis on its role of regulating metabolic dysfunction-associated steatohepatitis (MASH), a key predisposing factor for HCC, new treatment strategies targeting AEG-1, and challenges associated with analyzing this intriguing molecule. Full article
(This article belongs to the Special Issue Molecular Markers and Targeted Therapy for Hepatobiliary Tumors)
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26 pages, 1560 KiB  
Review
Exploring the Role of GITR/GITRL Signaling: From Liver Disease to Hepatocellular Carcinoma
by Stavros P. Papadakos, Elena Chatzikalil, Georgios Vakadaris, Lampros Reppas, Konstantinos Arvanitakis, Theocharis Koufakis, Spyros I. Siakavellas, Spilios Manolakopoulos, Georgios Germanidis and Stamatios Theocharis
Cancers 2024, 16(14), 2609; https://doi.org/10.3390/cancers16142609 - 22 Jul 2024
Cited by 2 | Viewed by 2825
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver cancer and presents a continuously growing incidence and high mortality rates worldwide. Besides advances in diagnosis and promising results of pre-clinical studies, established curative therapeutic options for HCC are not currently available. Recent progress [...] Read more.
Hepatocellular carcinoma (HCC) is the most common primary liver cancer and presents a continuously growing incidence and high mortality rates worldwide. Besides advances in diagnosis and promising results of pre-clinical studies, established curative therapeutic options for HCC are not currently available. Recent progress in understanding the tumor microenvironment (TME) interactions has turned the scientific interest to immunotherapy, revolutionizing the treatment of patients with advanced HCC. However, the limited number of HCC patients who benefit from current immunotherapeutic options creates the need to explore novel targets associated with improved patient response rates and potentially establish them as a part of novel combinatorial treatment options. Glucocorticoid-induced TNFR-related protein (GITR) belongs to the TNFR superfamily (TNFRSF) and promotes CD8+ and CD4+ effector T-cell function with simultaneous inhibition of Tregs function, when activated by its ligand, GITRL. GITR is currently considered a potential immunotherapy target in various kinds of neoplasms, especially with the concomitant use of programmed cell-death protein-1 (PD-1) blockade. Regarding liver disease, a high GITR expression in liver progenitor cells has been observed, associated with impaired hepatocyte differentiation, and decreased progenitor cell-mediated liver regeneration. Considering real-world data proving its anti-tumor effect and recently published evidence in pre-clinical models proving its involvement in pre-cancerous liver disease, the idea of its inclusion in HCC therapeutic options theoretically arises. In this review, we aim to summarize the current evidence supporting targeting GITR/GITRL signaling as a potential treatment strategy for advanced HCC. Full article
(This article belongs to the Special Issue Molecular Markers and Targeted Therapy for Hepatobiliary Tumors)
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18 pages, 546 KiB  
Review
Immunotherapy as a Complement to Surgical Management of Hepatocellular Carcinoma
by Susan J. Kim, Kaelyn C. Cummins and Allan Tsung
Cancers 2024, 16(10), 1852; https://doi.org/10.3390/cancers16101852 - 12 May 2024
Cited by 1 | Viewed by 2239
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver tumor in adults, and the fourth leading cause of cancer-related deaths worldwide. While surgical and ablative therapies remain the standard of care in early localized disease, late presentation with advanced stages of disease, impaired [...] Read more.
Hepatocellular carcinoma (HCC) is the most common primary liver tumor in adults, and the fourth leading cause of cancer-related deaths worldwide. While surgical and ablative therapies remain the standard of care in early localized disease, late presentation with advanced stages of disease, impaired hepatic function, or local recurrence following surgical resection preclude operative management as the sole treatment modality in a subgroup of patients. As such, systemic therapies, namely immunotherapy, have become an integral part of the HCC treatment algorithm over the past decade. While agents, such as atezolizumab/bevacizumab, have well-established roles as first-line systemic therapy in intermediate- and advanced-stage HCC, the role of immunotherapy in disease amenable to surgical management continues to evolve. In this review, we will discuss the current evidence and aggregate impact of immunotherapy in the context of HCC amenable to surgical management, including its application in the neoadjuvant and adjuvant settings. Full article
(This article belongs to the Special Issue Molecular Markers and Targeted Therapy for Hepatobiliary Tumors)
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21 pages, 2238 KiB  
Review
Locoregional Therapies for Hepatobiliary Tumors: Contemporary Strategies and Novel Applications
by Andrei M. Jipa and Mina S. Makary
Cancers 2024, 16(7), 1271; https://doi.org/10.3390/cancers16071271 - 25 Mar 2024
Cited by 8 | Viewed by 1632
Abstract
A large majority of primary hepatobiliary tumors are hepatocellular carcinomas (HCC), with the remainer being cholangiocarcinoma. While surgical resection remains the gold standard treatment for hepatobiliary tumors, relatively few patients are operative candidates, and systemic treatments have limited effectiveness. Locoregional therapies offer significant [...] Read more.
A large majority of primary hepatobiliary tumors are hepatocellular carcinomas (HCC), with the remainer being cholangiocarcinoma. While surgical resection remains the gold standard treatment for hepatobiliary tumors, relatively few patients are operative candidates, and systemic treatments have limited effectiveness. Locoregional therapies offer significant promise in the management of HCC. Ablation and radioembolization may offer similar outcomes to surgery for early-stage hepatocellular carcinoma while radioembolization and chemoembolization are valuable in the management of advanced disease. There is significantly less evidence for the role of locoregional therapy in the treatment of cholangiocarcinoma, although it appears to be well tolerated. Full article
(This article belongs to the Special Issue Molecular Markers and Targeted Therapy for Hepatobiliary Tumors)
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16 pages, 286 KiB  
Review
Current Status of Targeted Therapy for Biliary Tract Cancer in the Era of Precision Medicine
by Takafumi Mie, Takashi Sasaki, Takeshi Okamoto, Takaaki Furukawa, Tsuyoshi Takeda, Akiyoshi Kasuga, Masato Ozaka and Naoki Sasahira
Cancers 2024, 16(5), 879; https://doi.org/10.3390/cancers16050879 - 22 Feb 2024
Cited by 5 | Viewed by 3407
Abstract
First-line chemotherapy has been established for advanced biliary tract cancer (BTC). However, few treatment options are available as second-line treatment. Advances in comprehensive genomic analysis revealed that nearly half of patients with BTC harbor targetable genetic alterations such as fibroblast growth factor receptor [...] Read more.
First-line chemotherapy has been established for advanced biliary tract cancer (BTC). However, few treatment options are available as second-line treatment. Advances in comprehensive genomic analysis revealed that nearly half of patients with BTC harbor targetable genetic alterations such as fibroblast growth factor receptor (FGFR), isocitrate dehydrogenase (IDH), BRAF, human epidermal growth factor receptor 2 (HER2), microsatellite instability (MSI)-high, neurotrophic tropomyosin receptor kinase (NTRK), rearranged during transfection (RET), and poly (adenosine diphosphate-ribose) polymerase (PARP). This review summarizes currently available options in precision medicine and clinical trials for patients with advanced BTC. Full article
(This article belongs to the Special Issue Molecular Markers and Targeted Therapy for Hepatobiliary Tumors)
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