Azizi Z, Er Urganci B, Acikbas I. Breast cancer stem cells and circulating tumor cells: Dual drivers of progression and relapse. World J Stem Cells 2025; 17(12): 112990 [DOI: 10.4252/wjsc.v17.i12.112990]
Corresponding Author of This Article
Zahra Azizi, Department of Medical Biology, Faculty of Medicine, Pamukkale University, Kinikli Road, Denizli 20160, Turkey. zazizi19@posta.pau.edu.tr
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Oncology
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Review
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This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Dec 26, 2025 (publication date) through Dec 31, 2025
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World Journal of Stem Cells
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1948-0210
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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
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Azizi Z, Er Urganci B, Acikbas I. Breast cancer stem cells and circulating tumor cells: Dual drivers of progression and relapse. World J Stem Cells 2025; 17(12): 112990 [DOI: 10.4252/wjsc.v17.i12.112990]
World J Stem Cells. Dec 26, 2025; 17(12): 112990 Published online Dec 26, 2025. doi: 10.4252/wjsc.v17.i12.112990
Breast cancer stem cells and circulating tumor cells: Dual drivers of progression and relapse
Zahra Azizi, Buket Er Urganci, Ibrahim Acikbas
Zahra Azizi, Buket Er Urganci, Ibrahim Acikbas, Department of Medical Biology, Faculty of Medicine, Pamukkale University, Denizli 20160, Turkey
Author contributions: Azizi Z performed the majority of the writing; Urganci BE and Acikbas I prepared and designed the outline and coordinated the writing of the paper.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Zahra Azizi, Department of Medical Biology, Faculty of Medicine, Pamukkale University, Kinikli Road, Denizli 20160, Turkey. zazizi19@posta.pau.edu.tr
Received: August 12, 2025 Revised: September 27, 2025 Accepted: November 6, 2025 Published online: December 26, 2025 Processing time: 135 Days and 18 Hours
Abstract
Breast cancer remains a leading cause of cancer-related death in women worldwide. Emerging evidence highlights the central roles of breast cancer stem cells (BCSCs) and circulating tumor cells (CTCs) in tumor initiation, progression, therapeutic resistance, and metastasis. BCSCs self-renew and drive intertumoral heterogeneity, while CTCs disseminate from primary tumors into the bloodstream, seeding distant sites. These populations share molecular features, including stemness and epithelial-mesenchymal transition markers, supporting the concept that a subset of CTCs acquires stem-like traits, enhancing metastatic potential and resistance to standard therapies. This review synthesizes current knowledge on BCSC molecular programs, key signaling pathways (e.g., Wnt, Notch, Hedgehog, Janus kinase/signal transducer and activator of transcription), and microenvironmental interactions that sustain stemness. It also examines mechanisms of CTC intravasation, state-dependent detection strategies, and their diagnostic and prognostic utility. We further highlight the adaptive plasticity of cancer stem cell-like CTCs, their contributions to drug resistance, and opportunities to target these phenotypes for personalized treatment. Clarifying the biological links between BCSCs and CTCs could enable earlier detection of hidden metastasis and inform combination therapies aimed at both stemness and dissemination. As multimodal detection improves and functional profiling matures, integrating BCSC/CTC analyses into routine care may refine risk stratification and guide individualized management.
Core Tip: This review emphasizes the dual functions of breast cancer stem cells and circulating tumor cells (CTCs) in the advancement of tumors, resistance to treatment, and metastasis. We examine their common molecular characteristics, including self-renewal and epithelial-mesenchymal transition, as well as their interaction with the tumor microenvironment. The paper also covers the current technologies for detecting CTCs and their clinical applications. Gaining an understanding of the dynamic relationship between breast cancer stem cells and CTCs provides valuable insights into the early detection of metastasis and may inform the development of personalized treatment strategies for breast cancer patients.
