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Transforming Liver Cancer Care: From Molecular Understanding to Novel Therapeutic Strategies

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: 31 August 2026 | Viewed by 2801

Special Issue Editor

Dr. Chencheng Xie

E-Mail Website
Guest Editor
Sanford School of Medicine, University of South Dakota, Sioux Falls, SD, USA
Interests: hepatology; gastroenterology; hepatocellular carcinoma; metabolic dysfunction-associated steatotic liver disease; alcohol-associated liver disease; liver transplantation

Special Issue Information

Dear Colleagues,

We are pleased to announce the call for submissions to a Special Issue of Cancers focusing on the theme of "Transforming Liver Cancer Care: From Molecular Understanding to Novel Therapeutic Strategies". Liver cancer, particularly hepatocellular carcinoma (HCC), remains a leading cause of cancer-related deaths worldwide. Advances in molecular research, biomarkers, and targeted therapies are transforming diagnosis and treatment. This Special Issue invites original research and reviews on the following:

  • Molecular and genetic mechanisms driving liver cancer.
  • Biomarkers for early detection, prognosis, and treatment response.
  • Innovations in targeted therapy, immunotherapy, and combination strategies.
  • Tumor microenvironment and therapeutic resistance.
  • Translational research bridging lab discoveries to clinical practice.

By showcasing emerging strategies, this collection aims to enhance liver cancer care and improve patient outcomes. We welcome your contributions.

Dr. Chencheng Xie
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-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.

Publisher's Notice

The Special Issue, together with its publications, has been removed from Section Tumor Microenvironment on 15 January 2026. The publications remain available in the regular issues in which they were originally published. The Editorial Office confirms that these articles adhered to MDPI's standard editorial process (https://www.mdpi.com/editorial_process).

Keywords

  • liver cancer
  • molecular research
  • biomarkers
  • targeted therapy
  • translational research

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

Published Papers (2 papers)

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Research

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19 pages, 1010 KB  
Article
Predicting and Managing Hepatocellular Carcinoma Recurrence After Liver Transplant: A Single-Center Experience 2012–2024
by Jesse Civan, Madison Force, Ali Raza Shaikh, Adam Bodzin and Daniel Lin
Cancers 2026, 18(5), 721; https://doi.org/10.3390/cancers18050721 - 24 Feb 2026
Viewed by 699
Abstract
Background: Hepatocellular carcinoma (HCC) is a major cause of mortality in the United States, but it can be cured with orthotopic liver transplant (OLT) in selected patients. Despite curative intent, post-OLT recurrence can occur in up to 15% of patients. The need [...] Read more.
Background: Hepatocellular carcinoma (HCC) is a major cause of mortality in the United States, but it can be cured with orthotopic liver transplant (OLT) in selected patients. Despite curative intent, post-OLT recurrence can occur in up to 15% of patients. The need for a program of post-OLT surveillance is widely accepted but the specifics of an optimal program have not been established. There is interest in identifying lower-risk cohorts of patients in whom an abbreviated strategy of surveillance may prove adequate, utilizing tools such as the RETREAT score. Unique challenges are posed in the post-transplant population regarding safety and tolerability of systemic therapy for HCC recurrence, suggesting early detection is beneficial. Methods: This was a single-center retrospective analysis of characteristics and outcomes for all patients undergoing transplant at our center between 1 January 2012 and 31 December 2024. Diagnosis of HCC was determined by histological confirmation or Liver Imaging and Reporting Data System (LI-RADS) 5 findings on contrast-enhanced cross-sectional imaging. RETREAT scores were calculated for all patients. Results: During the study period, 923 transplants were performed, of which 329 (35.6%) were for HCC. Post-OLT recurrence occurred in 36 (10.9%) of these. Recurrence was associated with the presence of any viable tumor on explant surgical pathology, the presence of a viable tumor beyond Milan Criteria, the presence of microvascular invasion, a larger diameter of viable tumor on explant, and a higher RETREAT score. Although higher RETREAT scores were associated with post-OLT recurrence, one-third of patients who experienced post-OLT recurrence had RETREAT scores of 0 or 1. RETREAT scores did not correlate with the time interval between transplant and HCC recurrence. Systemic therapy proved challenging, with 10/25 patients receiving systemic therapy for post-OLT recurrence having to stop or alter regimens due to the severity of adverse effects. Conclusions: The rates of post-transplant recurrence and the experience of patients managed with systemic therapy for post-OLT recurrence in our experience were in line with previously published data. Due to the overall low RETREAT scores, the sensitivity of the RETREAT score in identifying patients at risk for post-OLT recurrence was limited, and the low RETREAT score had very limited incremental negative predictive value for identifying a low-risk population. This suggested that a broad screening strategy for post-OLT recurrence may be better than a personalized strategy in which patients with low RETREAT scores receive abbreviated surveillance. Full article
(This article belongs to the Special Issue Transforming Liver Cancer Care: From Molecular Understanding to Novel Therapeutic Strategies)
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Review

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31 pages, 1423 KB  
Review
Transforming Liver Cancer Therapy: Integrating Molecular Profiling with Precision and Transplant-Based Care
by Seoung Hoon Kim
Cancers 2025, 17(22), 3671; https://doi.org/10.3390/cancers17223671 - 16 Nov 2025
Cited by 1 | Viewed by 1510
Abstract
Liver cancer, predominantly hepatocellular carcinoma (HCC), remains a leading cause of cancer-related mortality worldwide. Although systemic therapies have advanced in recent years, overall survival remains limited for many patients. A deeper understanding of the molecular and immunological landscape of HCC has driven the [...] Read more.
Liver cancer, predominantly hepatocellular carcinoma (HCC), remains a leading cause of cancer-related mortality worldwide. Although systemic therapies have advanced in recent years, overall survival remains limited for many patients. A deeper understanding of the molecular and immunological landscape of HCC has driven the emergence of new therapeutic paradigms, from molecularly targeted agents to immune checkpoint blockade. Concurrently, innovations in liver transplantation, liquid biopsy, and multi-omics profiling are reshaping the therapeutic algorithm for selected candidates. This review summarises recent progress in molecular classification, tumour microenvironment mapping, and immune modulation, and examines how these translational insights are redefining clinical practice. Particular emphasis is placed on the integration of molecular markers into transplant eligibility, downstaging strategies, and post-transplant immunosuppression, providing a comprehensive, precision-oriented framework that bridges basic discovery and patient-centred care. Full article
(This article belongs to the Special Issue Transforming Liver Cancer Care: From Molecular Understanding to Novel Therapeutic Strategies)
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