Faculty, Staff and Student Publications

Language

English

Publication Date

3-1-2026

DOI

10.1002/advs.202508934

PMID

41610338

PMCID

PMC12970226

PubMedCentral® Posted Date

1-29-2026

PubMedCentral® Full Text Version

Post-print

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.

Keywords

Tumor Microenvironment, Humans, Pancreatic Neoplasms, Lab-On-A-Chip Devices, Carcinoma, Pancreatic Ductal, Organoids, Precision Medicine, Antineoplastic Agents, microfluidic, organ on chip, pancreatic cancer, patient derived organoids, tumor microenvironment

Published Open-Access

yes

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