整合CTC分析以表征肿瘤进展并支持面向下一代癌症治疗的广泛多组学生物标志物平台

Background: Circulating tumor cells (CTCs) offer a minimally invasive approach to evaluate tumor progression, metastatic potential, and therapeutic response. CytoGen's SMART BIOPSY™ platform, based on high-definition HDM Chip technology, enables sensitive CTC capture from non-clinical and clinical samples. Establishing the translational value of CTC dynamics in non-clinical efficacy studies is essential for developing biomarkers that can support clinical trial design and IND filing. Methods: To investigate the relationship between CTCs, tumor burden, and metastasis, xenograft models were generated using both non-metastatic and metastatic human cancer cell lines. Blood samples were collected longitudinally during tumor growth and after therapeutic intervention. CTCs were isolated using the SMART BIOPSY™ platform and evaluated by immunofluorescence (IF) to enumerate total CTCs and quantify target-marker-positive CTC populations. Tumor size and metastatic progression were assessed through imaging and necropsy to determine correlations with CTC dynamics. Results: IF-based analysis demonstrated a clear correlation between CTC counts and tumor burden, with metastatic models consistently yielding higher CTC numbers than non-metastatic models. Importantly, therapeutic treatment that led to tumor reduction produced a significant decrease in target-marker-positive CTCs, indicating that SMART BIOPSY™ sensitively reflects pharmacodynamic changes. These findings validate the platform's reliability for monitoring tumor progression and early treatment response in non-clinical efficacy studies. Conclusions: While this study focused on IF-based CTC characterization, the SMART BIOPSY™ platform is fully compatible with a broad multi-omics workflow, including scRNA-seq, FISH, NGS, immunofluorescence panels, and proteomics, enabling comprehensive biomarker discovery for metastasis and drug resistance. The translational insights obtained from non-clinical CTC analyses can be directly leveraged in IND filing, supporting patient stratification strategies and pharmacodynamic monitoring in early-phase clinical trials. Collectively, SMART BIOPSY™ provides a robust bridge that connects non-clinical efficacy studies with clinical drug development, establishing a versatile and expandable platform for next-generation oncology therapeutics.