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

Area of Science:

• Biomedical Engineering
• Cancer Research
• Microfluidics

Background:

• Tumor heterogeneity and drug resistance impede cancer therapy effectiveness.
• There is a critical need for patient-specific preclinical models to overcome these limitations.
• Current models often fail to replicate the complex tumor microenvironment and drug delivery dynamics.

Purpose of the Study:

• To develop and validate a microfluidic tumor-on-chip (TOC) platform.
• To integrate patient-derived organoids with a functional endothelial barrier to mimic tumor vasculature.
• To enable physiologically relevant evaluation of therapeutic efficacy, toxicity, and drug delivery.

Main Methods:

• Development of a microfluidic platform integrating patient-derived organoids and an endothelial barrier.
• Utilizing liquid flow to simulate vascular drug delivery into tumor tissue.
• Assessment of immune cell migration and drug response patterns at single-cell resolution.

Main Results:

• The TOC platform successfully recreated drug delivery from vasculature into tumor tissue.
• The model captured cellular features of treatment resistance and pathway rewiring in pancreatic cancer.
• Drug response patterns showed a trend toward alignment with patient clinical outcomes in an exploratory analysis.
• The platform demonstrated utility in assessing immune cell migration.

Conclusions:

• The developed tumor-on-chip platform offers a scalable and clinically relevant tool for cancer research.
• It enables the study of treatment response mechanisms under physiologically constrained drug delivery conditions.
• This technology can advance the evaluation of therapeutic efficacy and toxicity in patient-specific contexts.