From Liquid Biopsy to Therapy: The Rising Role of Circulating Tumor Cell Clusters in Cancer Progression
Mousarreza Shiri,1Mohammadreza Sharifi,2,*
1. Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran 2. Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
Introduction: Circulating tumor cell (CTC) clusters constitute a specialized subset of tumor-derived cells circulating in the bloodstream, with metastatic potential far exceeding that of individual CTCs. These multicellular aggregates preserve epithelial traits while exhibiting mesenchymal plasticity, stem-like features, and distinct epigenetic modifications, collectively enhancing their survival, immune evasion, and ability to establish secondary lesions.
Methods: Recent advances in liquid biopsy technologies—including microfluidic enrichment, single-cell omics, and spatial transcriptomics—have provided unprecedented insights into the molecular and functional properties of CTC clusters. Clinically, their presence and dynamics are closely associated with aggressive disease progression, therapeutic resistance, and adverse prognosis across multiple cancer types.
Results: Emerging therapeutic strategies aim to exploit the vulnerabilities of these clusters by disrupting intercellular adhesion, modulating cooperative signaling, or altering the circulatory microenvironment to limit metastatic spread.
Conclusion: This review synthesizes current understanding of CTC cluster biology, highlights state-of-the-art detection methods, and discusses translational opportunities that may transform these clusters from passive biomarkers into actionable targets in precision oncology.