Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
11.4
6.0
Journals
Cells
Special Issues
Pediatric Liver Tumors: Molecular Mechanisms and Therapeutic Strategies
share announcement

Pediatric Liver Tumors: Molecular Mechanisms and Therapeutic Strategies

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: 30 September 2026 | Viewed by 3375

Editor

Prof. Dr. Edward V. Prochownik

E-Mail Website
Guest Editor
Section of Hematology and Oncology, Children's Hospital of Pittsburgh, Rangos Research Center, Pittsburgh, PA, USA
Interests: hepatoblastoma; MYC oncogenes; tumor suppressors; molecular oncology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Primary liver tumors in children are relatively rare, with hepatoblastoma being the most common. Hepatoblastoma (HB) is a rare yet highly aggressive primary liver malignancy that predominantly affects children under four years of age. Despite significant improvements in survival rates for low-risk patients through modern multidisciplinary treatments, the prognosis for recurrent, high-risk, or metastatic HB remains poor. Moreover, traditional chemotherapy continues to face challenges related to toxicity and drug resistance. In recent years, advancements in high-throughput sequencing and molecular pathology have shed light on the molecular characteristics of HB. Notably, the aberrant activation of key pathways such as Wnt/β-catenin and Hippo/YAP has been identified as a core mechanism driving HB development. These insights offer promising new avenues for the development of targeted therapies and personalized treatment strategies. In addition, rare types such as fibrolamellar carcinoma (FLC) and hepatocellular carcinoma (HCC) are also research subjects in this field.

At the genetic level, certain syndromes, such as familial adenomatous polyposis (FAP), Beckwith-Wiedemann syndrome (BWS), and hereditary tyrosinemia, are associated with susceptibility to liver tumors in children, and their molecular mechanisms are increasingly attracting attention. Current research is dedicated to elucidating the intrinsic mechanisms of tumorigenesis from the perspectives of cell signaling regulation, abnormal gene expression, and epigenetic modifications.
This special issue will focus on the cellular biological mechanisms and recent advances in the treatment of pediatric liver tumors, particularly hepatoblastoma. This includes, but is not limited to, the following:

  1. Abnormal cell signaling pathways in pediatric liver cancers and targeted intervention strategies.
  2. The application of biomarkers in the treatment of primary liver tumors in children.
  3. The role of molecular targets in differentiating hepatoblastoma, hepatocellular carcinoma, and other rare pediatric liver tumors.
  4. The cellular biological significance of genomics in identifying therapeutic targets and distinguishing between somatic and germline mutations.
  5. The development of new reagents such as cell lines, chemotherapeutic drugs or immuno-therapies that can be used to improve the study and/or treatment of pediatric liver cancers

Dr. Edward V. Prochownik
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 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. Cells 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 2700 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

  • hepatoblastoma
  • hepatocellular carcinoma
  • pediatric liver tumors
  • fibrolamellar carcinoma
  • Beck-with-Wiedmann syndrome
  • hereditary tyrosinemia
  • molecular mechanisms
  • therapeutic strategies

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • Reprint: MDPI Books provides the opportunity to republish successful Special Issues in book format, both online and in print.

Further information on MDPI's Special Issue policies can be found here.

Published Papers (3 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

16 pages, 4512 KB  
Article
Proteasome Targeting with Carfilzomib Induces Reactive Oxygen Species-Mediated Apoptosis in Hepatoblastoma
by Elena Johanna Weigl, Salih Demir, Alina Hotes, Emilie Indersie, Sophie Branchereau, Stefano Cairo and Roland Kappler
Cells 2026, 15(10), 864; https://doi.org/10.3390/cells15100864 - 9 May 2026
Viewed by 665
Abstract
Hepatoblastoma (HB) is the most common malignant liver tumor in children, yet therapeutic options remain largely confined to conventional chemotherapy. To identify novel therapeutic targets, we performed gene set enrichment analysis on three publicly available HB datasets and found consistent activation of the [...] Read more.
Hepatoblastoma (HB) is the most common malignant liver tumor in children, yet therapeutic options remain largely confined to conventional chemotherapy. To identify novel therapeutic targets, we performed gene set enrichment analysis on three publicly available HB datasets and found consistent activation of the proteasome pathway, with marked overexpression of the β5 proteolytic subunit encoded by PSMB5. High PSMB5 expression was associated with poor survival in adult hepatocellular carcinoma, highlighting the proteasome as a candidate for therapeutic vulnerability. Targeting the β5 proteolytic subunit with its selective inhibitor carfilzomib in HB patient-derived xenograft (PDX) models resulted in dose-dependent reductions in cell viability, proliferation, and clonogenic growth, accompanied by induction of apoptosis. Importantly, carfilzomib retained efficacy in three-dimensional PDX cultures, underscoring its activity in physiologically relevant tumor models. Bioinformatic analyses revealed that carfilzomib activates apoptosis and reactive oxygen species (ROS) signaling. Validation experiments in HB cells demonstrated increased ROS levels, with ROS induction correlating with drug sensitivity. Notably, pharmacological scavenging of ROS completely abrogated carfilzomib-induced cytotoxicity, establishing oxidative stress as a key mediator of therapeutic response. Together, these findings identify PSMB5 as a therapeutically actionable target in HB and support proteasome inhibition as a promising precision medicine strategy in HB. Full article
(This article belongs to the Special Issue Pediatric Liver Tumors: Molecular Mechanisms and Therapeutic Strategies)
►▼ Show Figures

Figure 1

15 pages, 2392 KB  
Article
Upregulation of the lncRNA MEG3 in Metastatic Hepatoblastoma
by Morgan L. Brown, Maryam G. Shaikh, Nazia Nazam, Ali M. Eakes, Pranava Nande, Abdulraheem Kaimari, Joel C. Opara, Jamie M. Aye, Karina J. Yoon and Elizabeth A. Beierle
Cells 2026, 15(4), 361; https://doi.org/10.3390/cells15040361 - 18 Feb 2026
Viewed by 854
Abstract
Hepatoblastoma is the predominant primary liver malignancy in children, and outcomes remain poor for patients with metastatic disease. Long non-coding RNAs (lncRNAs) regulate tumor behavior, but their role in metastatic hepatoblastoma is not well defined. This study investigates the expression and functional significance [...] Read more.
Hepatoblastoma is the predominant primary liver malignancy in children, and outcomes remain poor for patients with metastatic disease. Long non-coding RNAs (lncRNAs) regulate tumor behavior, but their role in metastatic hepatoblastoma is not well defined. This study investigates the expression and functional significance of the lncRNA, maternally expressed gene 3 (MEG3), in a metastatic hepatoblastoma model. RNA sequencing comparing the metastatic hepatoblastoma cell line, HLM_2, with its parental HuH6 cell line identified MEG3 as being significantly upregulated in metastatic cells. MEG3 expression was examined using hepatoblastoma patient datasets and validated using qPCR in cell lines, orthotopic tumors, and COA67 patient-derived xenografts. The effects of siRNA MEG3 knockdown in HLM_2 cells on clonogenicity, migration, and invasion were evaluated. The effects of MEG3 overexpression on migration and invasion were assessed in HuH6 cells. MEG3 was significantly upregulated in metastatic cells and orthotopic tumors compared with controls. MEG3 silencing reduced clonogenicity, tumorsphere formation, migration, and invasion. MEG3 overexpression increased migration and invasion. These findings indicate that MEG3 contributes to an aggressive tumor phenotype, highlighting the need for further examination into its mechanistic role in hepatoblastoma and its potential as a biomarker or therapeutic target. Full article
(This article belongs to the Special Issue Pediatric Liver Tumors: Molecular Mechanisms and Therapeutic Strategies)
►▼ Show Figures

Figure 1

Review

Jump to: Research

30 pages, 482 KB  
Review
Hepatoblastoma Cell Lines: Past, Present and Future
by Edward V. Prochownik, Colin M. Henchy and Huabo Wang
Cells 2025, 14(24), 2013; https://doi.org/10.3390/cells14242013 - 17 Dec 2025
Cited by 2 | Viewed by 1312
Abstract
Hepatoblastoma (HB), the most common pediatric liver malignancy, tends to be highly curable although advanced or recurrent disease has less favorable outcomes. Because patients are invariably <3–4 years of age, chemotherapies can cause significant long-term morbidities. Immortalized HB cell lines could be of [...] Read more.
Hepatoblastoma (HB), the most common pediatric liver malignancy, tends to be highly curable although advanced or recurrent disease has less favorable outcomes. Because patients are invariably <3–4 years of age, chemotherapies can cause significant long-term morbidities. Immortalized HB cell lines could be of great utility for drug screening, for the identification of novel therapeutic susceptibilities, and for studies requiring highly regulated and/or rapidly changing in vitro environments. However, HB research is hampered by a paucity of these lines that could be used for such purposes, with only two human cell lines being readily available, neither of which represents the most common HB molecular subtypes. Recently, immortalized cell lines have been derived from murine HBs that are driven by the most common oncogenes and tumor suppressors associated with human tumors. These comprise five distinct groups associated with the deregulation of each of the four possible combinations of oncogenic forms of the β-catenin, YAP and NRF2 transcription factors or the over-expression of MYC. All five groups share many of the attributes and molecular signatures of actual human HBs. In addition, they have been used for purposes as diverse as identifying novel molecular targets through the use of Crispr-based screens and the demonstration that some HB cells can trans-differentiate into endothelial cells that facilitate tumor growth. The experience gained from these models and advances in the propagation of human hepatocytes in mice suggests that it may soon be possible to generate bespoke human immortalized human cell lines. Full article
(This article belongs to the Special Issue Pediatric Liver Tumors: Molecular Mechanisms and Therapeutic Strategies)
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-3
Back to TopTop