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Liver Disease and Primary Liver Cancer: Translational Advances and Therapeutic...
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Liver Disease and Primary Liver Cancer: Translational Advances and Therapeutic Perspectives

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (20 March 2026) | Viewed by 951

Special Issue Editor

Dr. Cristian Turato

E-Mail Website
Guest Editor
Department of Molecular Medicine, University of Pavia, 27100 Pavia, Italy
Interests: HCC; CCA; liver fibrosis; organoids; biomarkers
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Liver disease and primary liver cancer remain major global health challenges, with hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) ranking among the most prevalent and lethal malignancies worldwide. Despite progress in diagnostic and therapeutic approaches, patient outcomes remain poor due to late detection, limited treatment efficacy, and high recurrence rates. A deeper understanding of the molecular mechanisms underlying liver disease progression and hepatocarcinogenesis is essential to enable effective translational applications.

This Special Issue will focus on molecular science and translational advances in liver disease and liver cancer, with emphasis on innovative models and therapeutic strategies. Areas of interest include molecular pathways of inflammation and fibrosis, genetic and epigenetic regulation of hepatocarcinogenesis, tumor microenvironment and immune modulation, and novel biomarkers for diagnosis and prognosis. The issue will also cover the development and application of advanced experimental systems, such as 3D models, organoids, and bioengineered platforms, which provide powerful tools for studying disease mechanisms and testing new therapies. Furthermore, contributions addressing targeted therapies, immunotherapy, and combinatorial treatment strategies are welcome.

By assembling high-quality studies in these areas, this Special Issue aims to provide an updated overview of molecular insights and translational perspectives, ultimately supporting the development of innovative approaches for prevention, diagnosis, and treatment of liver disease and liver cancer.

Dr. Cristian Turato
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-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • liver disease
  • hepatocellular carcinoma
  • cholangiocarcinoma
  • molecular mechanisms
  • translational research
  • 3D models and organoids
  • biomarkers and therapeutic strategies
  • MASH/MASLD: pathogenesis, diagnosis, and management
  • primary liver cancer: pathogenesis, detection, and treatment
  • inflammation in liver disease
  • 3D liver models
  • microbiota and liver disease
  • mechanisms of damage and repair: ischemia-reperfusion injury
  • cellular pathology in acute and chronic liver damage of different origin
  • biomarkers in liver disease: emerging methods and potential applications
  • immunology in the liver—from homeostasis to disease

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Published Papers (2 papers)

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Research

25 pages, 6076 KB  
Article
The Novel HSF1 Inhibitor NXP800 Exhibits Robust Antitumor Activity in Hepatocellular Carcinoma
by Sara M. Steinmann, Melania Lazzari, Augustinus Kleinle, Dora Pischedda, Antonio Cigliano, Grazia Galleri, Heiko Siegmund, Claudia Fischer, Salvatore Piscuoglio, Matthias Evert and Diego F. Calvisi
Int. J. Mol. Sci. 2026, 27(6), 2781; https://doi.org/10.3390/ijms27062781 - 19 Mar 2026
Viewed by 196
Abstract
Heat-shock factor 1 (HSF1) is a multifunctional transcription factor whose overexpression is associated with the development, progression, and aggressiveness of several tumor types, including hepatocellular carcinoma (HCC). In the present study, we thoroughly investigated the antitumor activity of NXP800, a recently developed HSF1 [...] Read more.
Heat-shock factor 1 (HSF1) is a multifunctional transcription factor whose overexpression is associated with the development, progression, and aggressiveness of several tumor types, including hepatocellular carcinoma (HCC). In the present study, we thoroughly investigated the antitumor activity of NXP800, a recently developed HSF1 inhibitor that is currently tested in clinical trials, on HCC growth. We discovered that NXP800 inhibits the cell growth of human HCC cell lines by reducing proliferation, inducing apoptosis, and causing DNA damage. At the metabolic level, NXP800 significantly decreased mitochondrial respiration, which was associated with extensive structural alterations in the mitochondria, and reduced glycolysis of HCC cells. At the molecular level, NXP800 administration led to the upregulation of the integrated stress response and downregulation of the E2F1 signaling cascade. In addition, NXP800 profoundly constrained the growth of HCC patient-derived organoids. Furthermore, NXP800 antitumor properties were significantly augmented when NXP800 was coupled with the DNA-damaging agent doxorubicin or the PARP inhibitor olaparib. Our investigation indicates that NXP800 has significant antitumor activity and might represent a promising therapeutic agent for the treatment of human HCC. Full article
(This article belongs to the Special Issue Liver Disease and Primary Liver Cancer: Translational Advances and Therapeutic Perspectives)
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22 pages, 2146 KB  
Article
Transcriptomic Profiling of MicroRNA and Non-Coding RNA from Whole Blood of African Americans with MASLD
by Tanmoy Mondal, Brent E. Korba, Christopher A. Loffredo, Coleman I. Smith, Ruth Quartey, Jasneet Sahota, Gemeyel Moses, Charles D. Howell, Gail Nunlee-Bland, Zaki A. Sherif and Somiranjan Ghosh
Int. J. Mol. Sci. 2026, 27(4), 1666; https://doi.org/10.3390/ijms27041666 - 9 Feb 2026
Viewed by 472
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), is a growing health concern, yet the role of non-coding RNAs (ncRNAs), including microRNAs (miRNAs), in its pathogenesis remains poorly understood. In this pilot study, we aimed to identify [...] Read more.
Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), is a growing health concern, yet the role of non-coding RNAs (ncRNAs), including microRNAs (miRNAs), in its pathogenesis remains poorly understood. In this pilot study, we aimed to identify significantly expressed miRNAs and ncRNAs and correlate transcriptomic patterns of the findings with previously identified coding gene expression profiles to explore potential regulatory mechanisms in MASLD. Participants were selected from an existing study population. We conducted transcriptomic profiling of miRNAs and other ncRNAs in whole-blood samples from African American (AA) individuals with MASLD and matched controls (n = 4 per group) as a discovery cohort. A subsequent qRT-PCR validation study was performed in 30 participants, including 14 individuals with MASLD and 16 controls. miRNA sequencing was performed by Zymo, USA, followed by miRNA extraction using the Zymo-Seq™ miRNA Library Kit. Differentially expressed miRNAs and ncRNAs were analyzed using Ingenuity Pathway Analysis (IPA) to identify associated biological pathways. A total of 1412 miRNAs and 5423 other ncRNAs were identified in this study. Among them, 35 miRNAs and 28 other ncRNAs exhibited significant differential expressions (fold-change cutoff 1.5, p < 0.05). miR-206 was consistently upregulated, whereas miR-1343-5p, miR-1299, miR-224-5p, and miR-193a-5p were downregulated across all samples. miR-206 upregulation and miR-185-3p/miR-224-5p/miR-218-5p downregulation were validated, associating with lipid metabolism impairment and hepatic fibrosis via the AMPK/TGF-β pathway, implicating ncRNA-mediated regulation. To our knowledge, this is the first whole-blood non-coding RNA transcriptomic study in AA MASLD, an under-represented population. This small-scale pilot study requires validation in large multi-ethnic cohorts to confirm generalizability. Full article
(This article belongs to the Special Issue Liver Disease and Primary Liver Cancer: Translational Advances and Therapeutic Perspectives)
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