MINI REVIEW article
Front. Pharmacol.
Sec. Gastrointestinal and Hepatic Pharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1671001
This article is part of the Research TopicMolecular Insights into Fatty Liver Disease: Pathogenesis, Progression, and Therapeutic StrategiesView all 4 articles
NASH-Related Hepatocellular Carcinoma: Current Therapeutic Approaches and the Emerging Role of Sodium Homeostasis as a Novel Targeting Strategy
Provisionally accepted
- Universita degli Studi del Piemonte Orientale Amedeo Avogadro Dipartimento di Scienze della Salute, Novara, Italy
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Non-Alcoholic Steatohepatitis (NASH) rates are progressively accelerating due to lifestyle changes, which contribute to increased Hepatocellular carcinoma (HCC) incidence. HCC accounts for 90% of liver cancer cases, which ranks as the sixth prevalent, and the third leading cause of cancer-related deaths globally. NASH-HCC outweighs the decline in viral hepatitis-HCC, leaving a gap in the available therapies. The limited overall survival in the current treatments invokes the necessity of exploring novel therapeutic strategies to improve the poor prognosis of HCC. The pH gradient is a hallmark of cancer and is associated with increased intracellular sodium. Elevating this accumulation of intracellular sodium with sodium ionophores, such as Monensin, leads to selective death of murine HCC cancer cells without affecting the functionality of vital organs and proliferating activity of normal and transformed tissues. This study synthesizes the status of HCC risk and management, its molecular landscape, and sheds light on exploiting the elevated accumulation of intracellular sodium as a novel therapeutic strategy against HCC.
Keywords: Hallmarks of cancer, Hepatocellular Carcinoma, Monensin, Non-alcoholic fatty liver disease, Cancer targeting treatment, sodium homeostasis, Warburg effect
Received: 22 Jul 2025; Accepted: 25 Aug 2025.
Copyright: © 2025 Ashkar, Fiorilla, Tasso and Carini. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Abdulsalam Ashkar, Universita degli Studi del Piemonte Orientale Amedeo Avogadro Dipartimento di Scienze della Salute, Novara, Italy
Rita Carini, Universita degli Studi del Piemonte Orientale Amedeo Avogadro Dipartimento di Scienze della Salute, Novara, Italy
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