Ashkar Abdulsalam, Fiorilla Simone, Tasso Francesco, Carini Rita
Department of Health Science Università del Piemonte Orientale, Novara, Italy.
Front Pharmacol. 2025 Sep 3;16:1671001. doi: 10.3389/fphar.2025.1671001. eCollection 2025.
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.
由于生活方式的改变，非酒精性脂肪性肝炎（NASH）的发病率正在逐步上升，这导致肝细胞癌（HCC）的发病率增加。HCC占肝癌病例的90%，在全球癌症发病率中排名第六，是癌症相关死亡的第三大主要原因。NASH-HCC超过了病毒性肝炎-HCC的下降幅度，使得现有治疗方法存在缺口。当前治疗中有限的总生存期促使人们有必要探索新的治疗策略，以改善HCC的不良预后。pH梯度是癌症的一个标志，与细胞内钠的增加有关。用离子载体（如莫能菌素）提高细胞内钠的积累会导致小鼠HCC癌细胞选择性死亡，而不影响重要器官的功能以及正常和转化组织的增殖活性。本研究综合了HCC的风险状况和管理、其分子格局，并阐明了利用细胞内钠的升高积累作为对抗HCC的新治疗策略。
