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Review
. 2025 Aug 11;43(8):1399-1422.
doi: 10.1016/j.ccell.2025.07.008. Epub 2025 Jul 31.

Circulating tumor cells: Blood-based detection, molecular biology, and clinical applications

Charles S Dai  1 , Avanish Mishra  2 , Jon Edd  2 , Mehmet Toner  3 , Shyamala Maheswaran  1 , Daniel A Haber  4
Affiliations
Review

Circulating tumor cells: Blood-based detection, molecular biology, and clinical applications

Charles S Dai et al. Cancer Cell. .

Abstract

Circulating tumor cells (CTCs) are cancer cells, shed from primary tumors or metastases into the bloodstream. The first non-invasive "liquid biopsy" for cancer monitoring, CTCs have been largely surpassed by circulating tumor DNA (ctDNA) for clinical applications, given the ease of DNA sequencing without specialized cell isolation methods. However, emerging rare cell capture technologies that can process larger blood volumes and enable advanced single-cell analyses may enhance the range and potential of CTC-based biomarkers. CTCs are increasingly valuable for assessing tumor heterogeneity, guiding protein biomarker-driven cancer immune therapies, and assessing heterogeneous drug resistance, as well as for detecting minimal disease. CTCs, thus, remain central to understanding cancer dissemination and are poised to offer complementary diagnostic roles in the application of minimally invasive liquid biopsies for cancer. Here, we review recent advances in the study of these rare circulating cancer cells and discuss current limitations and future directions.

Keywords: cancer metastasis; circulating tumor cells; ex vivo cancer models; liquid biopsy biomarkers; minimal residual disease; molecular diagnostics; rare cell technologies; tumor heterogeneity.

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Conflict of interest statement

Declaration of interests Massachusetts General Hospital has been granted patent protection for the inertial separation array and inertial focusing microfluidic technologies used for CTC isolation. M.T., D.A.H., and S.M. are co-founders of TellBio, a biotechnology company commercializing the CTC-iChip technology. All authors’ interests were reviewed and managed by Massachusetts General Hospital and Mass General Brigham in accordance with their conflict-of-interest policies.

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