Your new experience awaits. Try the new design now and help us make it even better

REVIEW article

Front. Immunol.

Sec. Cancer Immunity and Immunotherapy

This article is part of the Research TopicUnlocking Cancer's Secrets: Overcoming Drug Resistance in Cancer Stem CellsView all 3 articles

Cancer Stem Cells in Hepatocellular Carcinoma

Provisionally accepted
Dipesh Kumar YadavDipesh Kumar Yadav1*Rajesh Kumar YadavRajesh Kumar Yadav2Dr Alina SinghDr Alina Singh3Yi HuangYi Huang1Dandan BaoDandan Bao1Zhangwei YangZhangwei Yang1Hanzhang HuangHanzhang Huang1Yin JiangYin Jiang4Pengwei WangPengwei Wang1Sisi LinSisi Lin1Yongfei HuaYongfei Hua4Yiren HuYiren Hu1
  • 1Wenzhou People's Hospital, Wenzhou, China
  • 2The University of Louisiana Monroe College of Pharmacy, Monroe, United States
  • 3Parkland Medicare and Research Center, Janakpur, Nepal
  • 4Ningbo Medical Centre Lihuili Hospital, Ningbo, China

The final, formatted version of the article will be published soon.

Select one of your emails

You have multiple emails registered with Frontiers:

Notify me on publication

Please enter your email address:

If you already have an account, please login

You don't have a Frontiers account ? You can register here

Hepatocellular carcinoma (HCC) imposes a significant global cancer mortality burden, with conventional therapies (surgery, ablation, chemotherapy, radiotherapy) and newer modalities (targeted agents, immune checkpoint inhibitors) limited by therapeutic resistance. Notably, liver cancer stem cells (Liver-CSCs)—defined by their self-renewal and unlimited proliferative capacity—drive tumor initiation, metastasis, heterogeneity, and therapy resistance. This review synthesizes current knowledge on Liver-CSCs, focusing on their distinctive features, supporting microenvironments, signaling pathways, and therapy resistance mechanisms. We also examine novel therapeutic strategies targeting these cells. Clinically, we evaluate recent research, identify knowledge gaps, and suggest potential directions for advancing HCC therapies. Finally, we discuss how these insights may inform development of more effective treatments to improve clinical HCC management. Understanding Liver-CSC biology and treatment resistance mechanisms will enable better-tailored therapies to overcome these challenges and enhance patient outcomes.

Keywords: cancer stem cells, Liver cancer stem cells, Hepatocellular Carcinoma, Liver Cancer Treatment Resistance, Immunotherapy

Received: 14 Sep 2025; Accepted: 12 Nov 2025.

Copyright: © 2025 Yadav, Yadav, Singh, Huang, Bao, Yang, Huang, Jiang, Wang, Lin, Hua and Hu. 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: Dipesh Kumar Yadav, dr.dipesh163@gmail.com

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Supplementary Material