Microenvironmental Remodeling and Circadian Regulation-Driven Evolution of Circulating Tumor Cells and Targeted Intervention Strategies
DU Xing, WAN Fang*
CTCs (circulating tumor cells) are central to cancer metastasis and serve as important targets for liquid biopsies, offering crucial insights into tumor evolution and clinical management. The survival of CTCs in the bloodstream and their subsequent spread across organs depend on highly coordinated, dynamic evolutionary processes. Here, this article systematically reviews the biological foundations of CTCs, highlighting the essential roles of EMT (epithelial-mesenchymal transition) plasticity, epigenetic reprogramming, AR (anoikis resistance), and metabolic rewiring in maintaining CTC viability. Recent studies suggest that CTC shedding and dissemination are tightly regulated by circadian rhythms. Additionally, CTCs often cluster with microenvironmental components, such as platelets and immune cells-to form heterotypic multicellular groups. These clusters greatly enhance immune evasion and the efficiency of distant organ colonization. Thanks to rapid advances in microfluidics and single-cell multi-omics, high-sensitivity detection platforms now enable detailed analysis of spatial molecular landscapes. These technologies facilitate real-time monitoring of MRD (minimal residual disease), responses to targeted therapies, and the development of drug resistance. Future approaches targeting CTCs will likely focus on precisely disrupting AR pathways, reversing abnormal methylation, and inhibiting key metastatic drivers mediated by membrane proteins and exosomes. Integrating multidimensional liquid biopsy data offers the potential to drive a major shift in clinical protocols, ultimately enhancing precision oncology and improving cancer management.
CN
EN