Tumor-on-chip as a personalized platform for rapid drug testing in breast cancer.

Abstract

Breast cancer (BC) continues to pose major therapeutic challenges, emphasizing the need for functional models that can rapidly inform treatment selection. Patient-derived xenografts (PDXs) and organoids (PDOs) are valuable tools for precision oncology, but their clinical utility is limited by inconsistent success rates and lengthy timelines. Here, we develop a tumor-on-chip (ToC) platform enabling functional drug sensitivity profiling within 4 days. ToC models show high reproducibility and a strong concordance with in vivo PDX responses. Drug sensitivity is correctly identified in 88% of PDX-responsive cases, while resistance was detected in 91%, with no false positives at clinically relevant concentrations. We design a chip compatible with minimal BC biopsy material. Proof-of-concept studies on patient samples show that the platform can distinguish sensitive and resistant profiles. These findings support the translational potential of ToC models for rapid personalized drug profiling in BC, laying the ground for their integration into clinical decision-making workflows.