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Biomedicines
Special Issues
Hepatocellular Carcinoma: Diagnosis, Pathophysiology, and Treatment
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Hepatocellular Carcinoma: Diagnosis, Pathophysiology, and Treatment

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cancer Biology and Oncology".

Deadline for manuscript submissions: 31 March 2027 | Viewed by 175

Editor

Dr. Yung-Yeh Su

E-Mail Website
Guest Editor
National Institute of Cancer Research, National Health Research Institutes, Tainan 704016, Taiwan
Interests: hepato-pancreato-biliary cancers

Special Issue Information

Dear Colleagues,

Hepatocellular carcinoma (HCC) remains a global health challenge, consistently ranking as a leading cause of cancer-related mortality. We have witnessed a significant breakthrough in systemic therapy in HCC since 2017. While early-stage (BCLC 0/A) and advanced-stage (BCLC C) cases have established protocols, intermediate-stage (BCLC B) HCC represents a highly heterogeneous patient population that continues to spark intense clinical debate. Recent shifts in the therapeutic landscape—including the 2026 BCLC updates and the integration of immunotherapy—necessitate a re-evaluation of how we stage, treat, and manage this specific subgroup. This Special Issue will provide a comprehensive overview of recent breakthroughs in the diagnosis, pathophysiology, and management of HCC, with a dedicated emphasis on the complexities of BCLC B. We seek to explore the transition from traditional locoregional therapies to personalized, multi-modal strategies. Topics of interest include, but are not limited to, the following:

  • Pathophysiology: Molecular drivers and the role of the tumor microenvironment in intermediate-stage progression;
  • Diagnosis and Staging: Advances in MRI/CT imaging, liquid biopsies, and AI-driven diagnostic tools;
  • BCLC B Sub-stratification: Novel frameworks for identifying "TACE-unsuitable" patients;
  • Therapeutic Innovation: The synergy of TACE/TARE with systemic agents (e.g., ICI and anti-angiogenics);
  • Conversion Therapy: Strategies for downstaging BCLC B patients to curative-intent surgery or transplantation.

We invite original research articles and reviews that bridge the gap between bench-side pathophysiology and bedside clinical decision-making.

Dr. Yung-Yeh Su
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 short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

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-anonymized peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly 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 2600 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

  • intermediate stage
  • BCLC B
  • TACE ineligible
  • systemic therapy
  • immunotherapy

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Published Papers (2 papers)

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Research

34 pages, 5289 KB  
Article
Rewiring of Molecular Networks Induced by the Combination of Loratadine, Raloxifene, and Sorafenib Leads to the Identification of Clinically Relevant Therapeutic Targets in Hepatocellular Carcinoma
by Fernanda Villarruel-Melquiades, Nancy Santos-Martínez, Martha Noyola-Díaz, Estefanía de Jesús Terán-Sánchez, José Iván Serrano-Contreras, Luis Gerardo Zepeda-Vallejo, María Eugenia Mendoza-Garrido, Julio Isael Pérez-Carreón, Cecilia Bañuelos, Georgina Hernández-Montes and Javier Camacho
Biomedicines 2026, 14(9), 1898; https://doi.org/10.3390/biomedicines14091898 - 25 Aug 2026
Abstract
Background/Objectives: Hepatocellular carcinoma (HCC) is the most prevalent primary liver tumor and is often diagnosed at advanced stages with very poor therapeutic response, leading to high mortality. Thus, new therapeutic strategies and biomarkers are urgently needed. We previously showed that the combination [...] Read more.
Background/Objectives: Hepatocellular carcinoma (HCC) is the most prevalent primary liver tumor and is often diagnosed at advanced stages with very poor therapeutic response, leading to high mortality. Thus, new therapeutic strategies and biomarkers are urgently needed. We previously showed that the combination of loratadine, raloxifene, and sorafenib exerts synergistic cytotoxicity on HCC cells. Here, we explored potential molecular mechanisms underlying the anticancer effects of this combination using multiomics analyses. Methods: We performed proteomic analyses based on mass spectrometry, transcriptomic analyses using the Clariom D Plus human microarray (Affymetrix), and metabolomic analyses based on nuclear magnetic resonance to investigate the profile changes induced by the drug combination in HuH7 cells. Bioinformatic analyses were applied to associate the omics changes with biological functions, molecular interactions, and clinical relevance in terms of patient survival. Results: We identified several molecules whose expression changed in response to treatment across the three omics profiles analyzed. Some of them were found to be involved in hallmarks of cancer, including sustained proliferation, evasion of growth suppressors, and resistance to cell death. Integrated multi-omics analyses revealed that the drug combination suppresses critical oncogenic drivers (C7orf50, NUP188, and HS2ST1) and that the mitotic cell cycle process, DNA synthesis and cholesterol biosynthesis are the primary pathways affected. Protein–protein interaction analysis revealed five key hubs (KIF2C, PCNA, TRIP13, NDC80, and RPA3), whose expression in HCC is associated with poor clinical prognosis. Conclusions: The combined treatment rewired molecular networks involved in HCC progression. These findings identify clinically relevant molecular targets associated with poor prognosis and provide mechanistic insights into the synergistic anticancer activity of this drug combination. Full article
(This article belongs to the Special Issue Hepatocellular Carcinoma: Diagnosis, Pathophysiology, and Treatment)
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12 pages, 1113 KB  
Article
Feasibility of Conventional Abdominal Ultrasound for Monitoring Tumor Size After Stereotactic Body Radiotherapy for Hepatocellular Carcinoma
by Masayuki Ueno, Yohei Yamanouchi, Hideki Hanazawa, Hiroyuki Takabatake, Takahisa Kayahara, Youichi Morimoto, Satoshi Itasaka, Hirokazu Mouri and Motowo Mizuno
Biomedicines 2026, 14(9), 1893; https://doi.org/10.3390/biomedicines14091893 - 25 Aug 2026
Abstract
Background/Objectives: Stereotactic body radiotherapy (SBRT) is increasingly used for hepatocellular carcinoma (HCC) that is unsuitable for surgery, radiofrequency ablation (RFA), or transplantation. Although current evidence for imaging assessment after SBRT is largely based on contrast-enhanced computed tomography (CT) or magnetic resonance imaging [...] Read more.
Background/Objectives: Stereotactic body radiotherapy (SBRT) is increasingly used for hepatocellular carcinoma (HCC) that is unsuitable for surgery, radiofrequency ablation (RFA), or transplantation. Although current evidence for imaging assessment after SBRT is largely based on contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI), repeated contrast-enhanced imaging may be difficult to perform at every routine follow-up visit. Thus, we evaluated whether conventional abdominal ultrasound (US) can monitor tumor size after SBRT for HCC. Methods: We retrospectively reviewed 67 consecutive patients who underwent SBRT for HCC at our institution between January 2015 and October 2020. After excluding patients treated for local recurrence after RFA or transarterial chemoembolization, those whose lesions were not visible on pretreatment US, and those without follow-up US within one year, 32 patients with 32 nodules were analyzed. Tumor visibility and size changes on US were assessed before treatment and at <6, 6–12, and 12–18 months after SBRT. Results: The treated lesion was identified as a discrete nodule on US in 100% (15/15; 95% CI, 78.2–100%), 75.0% (18/24; 95% CI, 53.3–90.2%), and 50.0% (8/16; 95% CI, 24.7–75.3%) of examinations at <6, 6–12, and 12–18 months, respectively. In all cases in which the lesion was no longer measurable on US, contrast-enhanced CT/MRI showed complete or partial response. Local tumor progression occurred in one patient (3.1%) during a median follow-up of 24.1 months; in this patient, interval enlargement was first detected by US 3.7 months after SBRT and was subsequently confirmed by dynamic CT/MRI. Conclusions: These descriptive findings suggest that in selected patients with lesions clearly visible on pretreatment US, conventional abdominal US may provide complementary morphologic information during the first year after SBRT when used alongside periodic dynamic CT/MRI. Prospective validation is required before routine implementation. Full article
(This article belongs to the Special Issue Hepatocellular Carcinoma: Diagnosis, Pathophysiology, and Treatment)
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