REVIEW article
Front. Genet.
Sec. Cancer Genetics and Oncogenomics
Volume 16 - 2025 | doi: 10.3389/fgene.2025.1669741
This article is part of the Research TopicUnraveling Breast Cancer Complexity: Insights from Single-Cell Sequencing and Spatial TranscriptomicsView all 9 articles
Single-Cell Transcriptomics in Metastatic Breast Cancer: Mapping Tumor Evolution and Therapeutic Resistance
Provisionally accepted
- 1Breast Center, Baotou City Cancer Hospital, Baotou 014000, Inner Mongolia, China, Baotou, China
- 2Operating Room, Baotou City Cancer Hospital, Baotou 014000, Inner Mongolia, China, Baotou, China
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Metastatic breast cancer (MBC) remains the primary cause of mortality in breast cancer patients, driven by tumor heterogeneity, cellular evolution, and therapy-resistant clones. Traditional bulk transcriptomics, although informative, fail to capture rare subpopulations and context-specific gene expression, which are crucial for understanding disease progression. Single-cell transcriptomics (SCT) has emerged as a transformative approach, enabling high-resolution analysis of individual cells to reveal tumor composition, lineage dynamics, and transcriptional plasticity. This review highlights how SCT reshapes our understanding of MBC by mapping tumor evolution, identifying cancer stem-like cells, and characterizing states of epithelial-mesenchymal transition. We explore how SCT reveals clonal and spatial heterogeneity, and how tumor microenvironment components, including immune, stromal, and endothelial cells, interact with cancer cells to support immune evasion and the formation of a metastatic niche. SCT also uncovers mechanisms of therapeutic resistance, including transcriptional reprogramming and the survival of drug-tolerant subpopulations. Integrating SCT with spatial transcriptomics and multi-omics platforms offers a comprehensive view of the MBC ecosystem and may uncover novel therapeutic targets. We further discuss the translational potential of SCT for biomarker discovery, liquid biopsy development, and precision oncology. We address current technical challenges and future directions for clinical application. SCT is poised to transform MBC research and guide next-generation therapeutic strategies.
Keywords: ScRNA-seq, metastatic breast cancer, tumor heterogeneity, therapeutic resistance, precision oncology
Received: 20 Jul 2025; Accepted: 06 Oct 2025.
Copyright: © 2025 Han, Li, Bai and Zhang. 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: Gangling Zhang, gangling-zhang@outlook.com
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