Circulating Tumor Cells in Cancer Metastasis

Cancer metastasis involves the dissemination of malignant cells from a primary tumour to distant organs, and circulating tumour cells (CTCs) are the pivotal agents in this process. Shed into the bloodstream or lymphatic system, CTCs may travel individually or as multicellular clusters, withstand shear stress, evade immune surveillance and colonise secondary sites. Their rarity and heterogeneity reflect complex interactions with the tumour microenvironment and systemic factors. Technological advances in enrichment and detection now allow phenotypic and genomic characterisation of single CTCs, revealing markers of epithelial–mesenchymal transition, stemness and organotropism. Such insights have informed novel strategies to intercept metastatic spread, from targeted inhibitors that disrupt cell–cell adhesion in clusters to immunomodulatory approaches guided by immune checkpoint expression on CTCs. Beyond mechanistic elucidation, CTC enumeration and molecular profiling have emerged as minimally invasive biomarkers for early detection, prognosis assessment and real-time monitoring of therapeutic response. Collectively, research on CTC biology and technology transforms our understanding of metastasis, with the promise of personalised interventions that improve patient outcomes worldwide.

Research from Nature Portfolio

Recent studies have demonstrated the potential to therapeutically target CTC clusters. A first-in-human trial explored the repurposing of a cardiac glycoside to disrupt Na+/K+ ATPase-mediated adhesion within CTC aggregates, reporting a significant reduction in cluster size without adverse events and transcriptional downregulation of adhesion and cell-cycle genes. This proof-of-principle supports further development of refined inhibitors to impair cluster-driven metastasis. In foundational work on immune evasion, longitudinal monitoring of CTCs in patients receiving checkpoint blockade revealed that persistence of immunosuppressive ligand expression on CTCs correlates with progressive disease, whereas loss of such expression aligns with clinical benefit. These findings illustrate how real-time CTC profiling can inform mechanisms of therapy resistance and guide adaptive treatment strategies.

Circulating Tumor Cells in Cancer Metastasis publication trend

The graph below shows the total number of articles in circulating tumor cells in cancer metastasis across all publications each year (not limited to Nature Index journals).

Technical terms

Circulating tumour cell (CTC): A cancer cell that has detached from the primary tumour and entered the bloodstream or lymphatic system.

Epithelial–mesenchymal transition (EMT): A biological programme by which epithelial cells acquire mesenchymal traits, enhancing motility and invasiveness.

Liquid biopsy: A minimally invasive analysis of circulating tumour-derived material, including CTCs, DNA and extracellular vesicles, in body fluids.

CTC cluster: A multicellular aggregate of CTCs that exhibits enhanced metastatic potential compared with single cells.

Single-cell sequencing: A method that profiles the genome or transcriptome of individual cells, revealing heterogeneity within CTC populations.

References

1. Digoxin for reduction of circulating tumor cell cluster size in metastatic breast cancer: a proof-of-concept trial. Nature Medicine (2025).
2. Monitoring PD-L1 positive circulating tumor cells in non-small cell lung cancer patients treated with the PD-1 inhibitor Nivolumab. Scientific Reports (2016).
3. Clinical application and detection techniques of liquid biopsy in gastric cancer. Molecular Cancer (2023).
4. The functional and clinical roles of liquid biopsy in patient-derived models. Journal of Hematology & Oncology (2023).