Molecular Targets and Combinatorial Therapeutics of Liver Cancer

Submission Deadline: 28 February 2026 (closed) View: 976 Submit to Special Issue

Guest Editors

Prof. Dr. Luis Cano

Email: luiscanoayestas@gmail.com

Affiliation: INRAE, CHU Pontchaillou, UMR 1241 NUMECAN, Universit de Rennes, 35033, France

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Research Interests: digital pathology & ai in cancer diagnosis, molecular oncology & biomarkers, hepatocellular carcinoma (HCC) and liver cancer therapeutics, tumor immunology & immunotherapy, neuro-oncology & glioblastoma, translational oncology & precision medicine, experimental models & clinical validation

Summary

Hepatocellular carcinoma (HCC), the most common form of primary liver cancer, remains a major global health burden with limited therapeutic success in advanced stages. Despite recent advances in targeted therapies and immunotherapies, patient prognosis is often poor due to tumor heterogeneity, drug resistance, and underlying liver dysfunction. This special issue explores the dynamic landscape of molecular targets and combinatorial therapeutic strategies in HCC, aiming to bridge preclinical discoveries with clinical applications. Particular emphasis is placed on novel oncogenic drivers, immune checkpoint modulators, epigenetic regulators, and metabolic vulnerabilities. Emerging combination strategiesintegrating kinase inhibitors, immune-based therapies, and RNA-targeted agentsare discussed for their potential to overcome monotherapy limitations. Furthermore, the role of multi-omics profiling, artificial intelligence, and spatial transcriptomics in identifying predictive biomarkers and therapeutic synergies is critically examined. By highlighting translational insights and future directions, this issue aims to catalyze the development of more effective, personalized interventions for liver cancer patients.

Keywords

hepatocellular carcinoma, molecular targets, combination therapy, immunotherapy, targeted therapy, biomarkers, drug resistance, tumor heterogeneity, kinase inhibitors, RNA therapeutics, spatial transcriptomics, precision oncology

Published Papers

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Open Access

REVIEW

Navigating the Labyrinth of Hepatocellular Carcinoma: Leveraging AI/ML for Precision Oncology
Abdul Manan, Sidra Ilyas
Oncology Research, DOI:10.32604/or.2026.074185
（This article belongs to the Special Issue: Molecular Targets and Combinatorial Therapeutics of Liver Cancer)
Abstract Hepatocellular carcinoma (HCC) remains a significant global health challenge, with therapeutic efficacy in advanced stages often limited by underlying liver dysfunction and adaptive resistance. In this review, the evolving landscape of molecular targets and combinatorial strategies is critically examined, with a particular focus on the transition from preclinical discovery to clinical application. While traditional molecular heterogeneity is acknowledged, the aim is to elucidate how emerging computational paradigms are redefining target discovery and therapeutic stratification in HCC. The primary purpose is to evaluate the role of Artificial Intelligence (AI) and Machine Learning (ML) as integrative tools… More >
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ARTICLE

The Effect of Metformin on Atezolizumab/Bevacizumab Treatment in Patients with Hepatocellular Carcinoma and Diabetes
Andrea Dalbeni, Marco Vicardi, Leonardo A. Natola, Alessandra Auriemma, Bernardo Stefanini, Caterina Vivaldi, Piera Federico, Andrea Polloni, Caterina Soldà, Lorenzo Lani, Ingrid Garajová, Stefano Tamberi, Stefania De Lorenzo, Fabio Piscaglia, Vincenzo Di Maria, Gianluca Masi, Sara Lonardi, Giovanni Brandi, Bruno Daniele, Franco Trevisani, Gianluca Svegliati-Baroni, Laura Schiada, Fabio Marra, Claudia Campani, Ciro Celsa, Giuseppe Cabibbo, Mariangela Bruccoleri, Massimo Iavarone, Leonardo Stella, Francesca R. Ponziani, Tiziana Pressiani, Lorenza Rimassa, Francesco Tovoli, David Sacerdoti
Oncology Research, Vol.34, No.4, 2026, DOI:10.32604/or.2026.073063
（This article belongs to the Special Issue: Molecular Targets and Combinatorial Therapeutics of Liver Cancer)
Abstract Objectives: The combination of atezolizumab plus bevacizumab (A+B) represents one of the standards first-line treatments for unresectable hepatocellular carcinoma (HCC). Metformin has garnered attention for its potential antitumour and immunomodulatory properties beyond glycaemic control. This study aimed to assess metformin’s impact in patients with type 2 diabetes mellitus (T2DM) receiving A+B therapy. Methods: This retrospective analysis of a prospectively-maintained multicentre database included 523 patients with HCC treated with A+B from the ARTE (Atezolizumab-bevacizumab Real-life Experience for Treatment of Hepatocellular Carcinoma) dataset across 18 Italian centres (May 2020–January 2024). We evaluated objective response rate (ORR), disease… More >

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COMMENTARY

Advances in Systemic Therapy for Unresectable Hepatocellular Carcinoma: Commentary on The Impact of the STRIDE Regimen in HIMALAYA Trial
Leenah Abdulgader, Abdullah Esmail
Oncology Research, Vol.34, No.3, 2026, DOI:10.32604/or.2026.069227
（This article belongs to the Special Issue: Molecular Targets and Combinatorial Therapeutics of Liver Cancer)
Abstract Unresectable hepatocellular carcinoma (HCC) remains a global challenge, with limited effective treatment options for advanced-stage disease. The HIMALAYA trial (phase III randomized study that evaluated the STRIDE regimen) introduced the Single Tremelimumab Regular Interval Durvalumab (STRIDE) regimen, an immunotherapy-based approach that achieved a median overall survival (OS) of 16.43 months compared to 13.77 months with sorafenib. While statistically significant, this ~2.7 months OS gain warrants scrutiny in light of STRIDE’s increased immune-related toxicity and cost. This commentary evaluates STRIDE’s impact within the broader landscape of first-line systemic therapy for unresectable HCC, alongside other regimens such… More >

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ARTICLE

CSRNP1 Promotes Apoptosis and Mitochondrial Dysfunction via ROS-Mediated JNK/p38 MAPK Pathway Activation in Hepatocellular Carcinoma
Huihui Shi, Lei Chen, Juan Huang, Xuejing Lin, Lei Huang, Min Tang, Kai Lu, Wenchao Wang, Maoling Zhu
Oncology Research, Vol.34, No.1, 2026, DOI:10.32604/or.2025.068737
（This article belongs to the Special Issue: Molecular Targets and Combinatorial Therapeutics of Liver Cancer)
Abstract Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. This study aimed to identify key genes involved in HCC development and elucidate their molecular mechanisms, with a particular focus on mitochondrial function and apoptosis. Methods: Differential expression analyses were performed across three datasets—The Cancer Genome Atlas (TCGA)-Liver Hepatocellular Carcinoma (LIHC), GSE36076, and GSE95698—to identify overlapping differentially expressed genes (DEGs). A prognostic risk model was then constructed. Cysteine/serine-rich nuclear protein 1 (CSRNP1) expression levels in HCC cell lines were assessed via western blot (WB) and quantitative reverse transcription polymerase chain reaction (qRT-PCR).… More >
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Molecular Targets and Combinatorial Therapeutics of Liver Cancer

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