# A Patient‐Derived Organ‐on‐Chip Platform for Modeling the Tumor Microenvironment and Drug Responses in Pancreatic Cancer

## TL;DR

A new organ-on-chip model for pancreatic cancer combines patient-derived cells with the tumor microenvironment to test personalized treatments and improve drug responses.

## Contribution

The integration of patient-derived organoids with stromal and immune cells in a microfluidic system to model the tumor microenvironment in pancreatic cancer.

## Key findings

- The OoC model replicates cancer-stroma interactions observed in pancreatic cancer in vivo.
- Targeting the stroma enhances the effectiveness of standard chemotherapy in the OoC platform.
- The platform enables assessment of immune checkpoint blockade for T cell cytotoxicity in PDAC.

## Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a fatal malignancy. Current conventional chemotherapeutics are inadequate in controlling the disease; hence, there is an urgent need for precision medicine. Ex vivo models that replicate the tumor and its microenvironment can advance precision medicine in PDAC. Patient‐derived organoids (PDOs) offer a promising solution by retaining the functional features of the tumor, allowing for individualized study of cancer biology and drug response. However, PDOs fall short in replicating the tumor microenvironment (TME), which includes various stromal and immune cells influencing tumor growth and chemoresistance. We hypothesize that combining PDO technology with organ‐on‐a‐chip (OoC) systems can enhance ex vivo cancer modeling. Here, we develop a patient‐derived platform by incorporating PDOs with key components of the TME (fibroblasts, endothelial cells, and immune cells) within a microfluidic system. This OoC model represents the crosstalk between cancer and stroma observed in PDAC in vivo. Targeting the stroma improves the effectiveness of standard chemotherapy in this OoC. Further, using this platform, we are able to model and assess the efficacy of immune checkpoint blockade for T cell cytotoxicity in PDAC. The OoC provides a pathophysiologically applicable system to support future investigations aimed at utilizing precision medicine and testing therapeutics in PDAC.

Researchers have developed a patient‐derived organ‐on‐a‐chip model for pancreatic cancer by integrating cancer cells with supportive stromal and immune cells inside a microfluidic device. This system mimics the tumor microenvironment, enabling personalized testing of chemotherapy and immunotherapy, and offering new insights into how targeting surrounding tissue may affect treatment responses.