Integrated CTC analysis to characterize tumor progression and enable broad multi-omics biomarker platforms for next-generation cancer Therapeutics

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.