Luo H, Yao MT, Yu MJ, Wang T. Differentiation-inducing therapy: A potential therapeutic strategy that targets liver cancer stem cells. World J Gastrointest Oncol 2026; 18(10): 124235 [DOI: 10.4251/wjgo.124235]
Corresponding Author of This Article
Tao Wang, MD, Department of General Surgery, General Hospital of Western Theater Command, No. 270 Rongdu Avenue, Chengdu 610083, Sichuan Province, China. wangtao301020@sina.com
Research Domain of This Article
Oncology
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review-article
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Luo H, Yao MT, Yu MJ, Wang T. Differentiation-inducing therapy: A potential therapeutic strategy that targets liver cancer stem cells. World J Gastrointest Oncol 2026; 18(10): 124235 [DOI: 10.4251/wjgo.124235]
World J Gastrointest Oncol. Oct 15, 2026; 18(10): 124235 Published online Oct 15, 2026. doi: 10.4251/wjgo.124235
Differentiation-inducing therapy: A potential therapeutic strategy that targets liver cancer stem cells
Hao Luo, Meng-Ting Yao, Min-Jie Yu, Tao Wang
Hao Luo, Meng-Ting Yao, Min-Jie Yu, Tao Wang, Department of General Surgery, General Hospital of Western Theater Command, Chengdu 610083, Sichuan Province, China
Co-first authors: Hao Luo and Meng-Ting Yao.
Author contributions: Luo H and Yao MT contributed equally to this manuscript and are co-first authors. Luo H, Yao MT, Yu MJ, and Wang T reviewed the literature; Luo H and Wang T contributed to manuscript drafting; Yao MT and Yu MJ prepared the illustration.
AI contribution statement: All of this manuscript were not edited using AI tools.
Supported by National Natural Science Foundation of China, No. 81502696; Program of General Hospital of Western Theater Command, No. 2021-XZYG-C33 and No. 2024-YGJC-A12; and Science & Technology Department of Sichuan Provence International Cooperation Program, No. 2019YFH0056.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Tao Wang, MD, Department of General Surgery, General Hospital of Western Theater Command, No. 270 Rongdu Avenue, Chengdu 610083, Sichuan Province, China. wangtao301020@sina.com
Received: June 10, 2026 Revised: July 12, 2026 Accepted: August 10, 2026 Published online: October 15, 2026 Processing time: 104 Days and 5.3 Hours
Abstract
Hepatocellular carcinoma (HCC) remains a major therapeutic challenges, largely owing to its high recurrence and metastasis rates. According to the liver cancer stem cells (LCSCs) theory, HCC can arise through two distinct pathways: Blocked differentiation of liver stem/progenitor cells (LSPCs) or dedifferentiation of hepatocytes. LCSCs constitute a core subpopulation of cells that drive tumor growth, drug resistance, and metastasis. Differentiation-inducing therapy is first applied to treat leukemia and generally extended to solid tumors, including HCC. In this review, we first focus on the potential therapeutic role of differentiation-inducing therapy in HCC via the blocked differentiation of LSPCs and the dedifferentiation of hepatocytes. We then survey a range of agents with differentiation-inducing therapeutic potential and discuss their underlying mechanism. Finally, we propose a novel strategy for differentiation-inducing therapy that may complement traditional treatment and potentially address the root drivers of malignant progression. This approach may offer new theoretical insights and identify actionable targets for precision medicine in HCC.
Core Tip: Differentiation-inducing therapy may be a potential strategy for hepatocellular carcinoma (HCC), as it can target both the arrested differentiation of liver stem/progenitor cells and the dedifferentiation of mature hepatocytes. We systematically retrieved and analyzed recent relevant research on liver cancer stem cells (LCSCs) origin and differentiation therapy, and we summarized how differentiation-inducing therapy plays therapeutic role based on the theory of LCSCs. In addition, we explored the potential molecules and agents with differentiation-inducing therapeutic effect, and assessed translational prospects and clinical applicability of these candidate agents for future HCC treatment.
