Better together: circulating tumor cell clustering in metastatic cancer

Circulating tumor cells (CTCs) are vital components of liquid biopsies for diagnosis of residual cancer, monitoring of therapy response, and prognosis of recurrence. Scientific dogma focuses on metastasis mediated by single CTCs, but advancement of CTC detection technologies has elucidated multicellular CTC clusters, which are associated with unfavorable clinical outcomes and a 20- to 100-fold greater metastatic potential than single CTCs. While the mechanistic understanding of CTC cluster formation is still in its infancy, multiple cell adhesion molecules and tight junction proteins have been identified that underlie the outperforming attributes of homotypic and heterotypic CTC clusters, such as cell survival, cancer sternness, and immune evasion. Future directions include high-resolution characterization of CTCs at multiomic levels for diagnostic/prognostic evaluations and targeted therapies.

Automated summary

CTC clusters play a crucial role in cancer, with a higher metastatic potential and unfavorable clinical outcomes compared to single CTCs. While the mechanism of CTC cluster formation is still unclear, certain cell adhesion molecules and tight junction proteins have been identified as key factors.