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 stemness, and immune evasion. Future directions include high-resolution characterization of CTCs at multiomic levels for diagnostic/prognostic evaluations and targeted therapies.

循环肿瘤细胞 (CTC) 是液体活检的重要组成部分，用于诊断残留癌症、监测治疗反应和预后复发。科学教条侧重于由单个 CTC 介导的转移，但 CTC 检测技术的进步已经阐明了多细胞 CTC 簇，这些簇与不利的临床结果相关，并且转移潜力比单个 CTC 高 20 到 100 倍。虽然对 CTC 簇形成的机制理解仍处于起步阶段，但已确定多个细胞粘附分子和紧密连接蛋白是同型和异型 CTC 簇的优异属性的基础，例如细胞存活、癌症干性和免疫逃避。