Precision tumor-on-chip for personalized assessment of drug efficacy and immune cell delivery

Abstract

Tumor heterogeneity and drug resistance limit the efficacy of cancer therapies and highlight the need for patient-specific preclinical models. Here, we develop a microfluidic tumor-on-chip (TOC) platform that integrates patient-derived organoids with a functional endothelial barrier and utilizes liquid flow to recreate drug delivery from the vasculature into tumor tissue. This system enables evaluation of therapeutic efficacy and toxicity under physiologically relevant conditions. Additionally, the platform is utilized to assess immune cell migration induced by tumor-derived factors in the absence of an endothelial barrier. In pancreatic cancer, the TOC model captures cellular features associated with treatment resistance and pathway rewiring at single-cell resolution, with drug response patterns showing a trend toward alignment with patient clinical outcomes in a limited, retrospective, exploratory setting. By simulating vascular drug transport, the platform provides a scalable and clinically relevant tool for studying treatment response mechanisms and evaluating drug responses under physiologically constrained delivery conditions.