Circulating tumor cells (CTCs) are malignant cells that have detached from primary or metastatic tumor sites and entered the peripheral bloodstream. As a critical component of liquid biopsy, the real-time information they provide offers a unique window into tumor metastasis mechanisms, therapeutic efficacy evaluation, and personalized treatment strategies. In recent years, technologies for generating organoids from CTCs have rapidly advanced, becoming powerful tools for investigating tumor metastasis and drug screening. However, challenges such as the scarcity of CTCs, difficulties in isolation and culture techniques, and low success rates in model construction continue to limit their clinical translation.
Research indicates that CTCs exhibit high heterogeneity, with surface markers and molecular characteristics varying significantly depending on tumor type and individual differences. Epithelial-mesenchymal transition (EMT) is a key mechanism by which CTCs detach from the primary tumor and enter circulation, endowing them with enhanced metastatic potential. CTCs interact with various blood cells—such as neutrophils, platelets, and macrophages—to regulate their survival, immune evasion, and metastatic capabilities. Compared to single CTCs, CTC clusters possess greater metastatic potential and higher prognostic value.
From a technical perspective, CTC isolation and enrichment strategies primarily include methods based on physical properties (such as size and density) and biological markers (such as EpCAM and CD45). Recently, the development of microfluidic chip technology has significantly improved the capture efficiency and purity of CTCs. Regarding culture, the successful generation of CTC-derived organoids depends on optimized conditions that simulate in vivo hypoxic environments, three-dimensional biological scaffolds, and specific growth factors.
CTC-derived organoids provide an indispensable model for in-depth analysis of CTC metastatic mechanisms, drug resistance, cancer stem cell characteristics, and interactions with the tumor microenvironment. Furthermore, in translational medicine, these organoids can be efficiently used for high-throughput drug screening, CRISPR gene-editing target validation, and the establishment of patient-derived tumor xenograft (CDX) models, significantly accelerating the development and optimization of anti-cancer therapies. Ultimately, in clinical applications, owing to their dynamic, minimally invasive, and reproducible culture features, CTC-derived organoids enable early diagnosis, prognosis assessment, drug resistance monitoring, and guidance for personalized treatment.
Although CTC-derived organoids demonstrate great potential in precision oncology, they currently face technical bottlenecks such as low capture efficiency, suboptimal culture success rates, and incomplete simulation of the tumor microenvironment. Future research should focus on developing high-precision capture strategies, optimizing culture systems, incorporating key components of the tumor microenvironment (such as immune cells and fibroblasts), and integrating multi-omics and artificial intelligence technologies to facilitate the translation of CTC organoids from basic research to clinical application.
In summary, CTC-derived organoids serve as a vital bridge connecting basic research and clinical practice. They not only offer unique advantages in elucidating tumor metastasis mechanisms but also hold broad application prospects in drug development and personalized therapy. With ongoing technological breakthroughs and the establishment of standardized protocols, CTC organoids are expected to drive precision oncology toward becoming more minimally invasive, dynamic, and individualized.
