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REVIEW article

Front. Cell Dev. Biol.

Sec. Stem Cell Research

Volume 13 - 2025 | doi: 10.3389/fcell.2025.1619597

This article is part of the Research TopicAdvances and Methods in Cancer Stem CellsView all 3 articles

Cancer Stem Cells in Personalized Therapy: Mechanisms, Microenvironment Crosstalk, and Therapeutic Vulnerabilities

Provisionally accepted
Ling YinLing Yin1,2,3,4,5Shoubing ZhouShoubing Zhou6Hongliang ZhangHongliang Zhang1Yuhua ShangYuhua Shang7Songquan WuSongquan Wu1*Tengchuan JinTengchuan Jin1,10,3,5,6,7,8,9*
  • 1Center of Disease Immunity and Intervention, College of Medicine, Lishui University, Lishui, China
  • 2College of Medicine, University of Florida, Gainesville, United States
  • 3Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United States
  • 4Institute of Health and Medicine, Hefei Comprehensive National Science Center, Hefei, China
  • 5Key Laboratory of Anhui Province for Emerging and Reemerging Infectious Diseases, Hefei, China
  • 6Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
  • 7Anhui Genebiol Biotech. Ltd., Hefei, China
  • 8Biomedical Sciences and Health Laboratory of Anhui Province, University of Science & Technology of China, Hefei, China
  • 9Clinical Research Hospital of Chinese Academy of Sciences (Hefei), University of Science and Technology of China, Hefei, China
  • 10Department of Infectious Diseases, The First Affiliated Hospital of USTC, Hefei, China

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Cancer stem cells (CSCs) drive tumor progression, therapy resistance, and metastasis through unique membrane biology, glycosylation patterns, and metabolic adaptations. CSCs exhibit a distinct glycocalyx profile enriched in hyaluronan, heparan sulfate, and sialylated glycans, facilitating immune evasion, adhesion, and survival. Key signaling pathways-Wnt/β-catenin, Hedgehog, Notch, JAK/STAT, TGF/SMAD, and PI3K/AKT/mTOR-regulate CSC stemness and therapeutic resistance. Emerging biomarkers (CD44, CD133, ALDH1, EpCAM) and targeted therapies (CAR-T cells, miRNA modulation, lipid metabolism inhibitors) show promise in disrupting CSC resilience. Advances in single-cell omics, CRISPR screening, and patient-derived organoids (PDOs) enhance CSC characterization and precision medicine applications. However, challenges remain in standardizing organoid cultures, replicating tumor microenvironments, and overcoming CSC plasticity. Integrating CSC-targeted strategies with conventional therapies may improve clinical outcomes by eradicating therapy-resistant populations and preventing relapse. This review underscores the need for innovative combination therapies to eradicate CSCs and improve clinical outcomes, while addressing challenges in biomarker validation, therapeutic resistance, and translational applications.

Keywords: cancer stem cells, metabolic reprogramming, Immune Evasion, Organoids, personalized therapy

Received: 28 Apr 2025; Accepted: 18 Jul 2025.

Copyright: © 2025 Yin, Zhou, Zhang, Shang, Wu and Jin. 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:
Songquan Wu, Center of Disease Immunity and Intervention, College of Medicine, Lishui University, Lishui, China
Tengchuan Jin, Center of Disease Immunity and Intervention, College of Medicine, Lishui University, Lishui, China

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