The PDAC-on-Chip for Pancreatic Cancer Research

5. March 2025 In Blog, Cancer, Disease-Modeling

The PDAC-on-Chip – A New Dimension in Pancreatic Cancer Research

Pancreatic ductal adenocarcinoma (PDAC) is characterized by a dense, fibrotic tumor microenvironment that interferes with drug delivery and helps evade the immune system. As a result, it is one of the most aggressive and deadly cancers with a five-year survival rate of only 13%, and limited treatment options.

Due to the very specific nature of the tumor environment, it is essential to have in vitro models that can reconstruct the crosstalk between tumor cells and the surrounding stroma. This is the only way to clearly assess the effectiveness of drugs. A new biochip developed by Dynamic42 and the team of Prof. Dr. Nicole Teusch at the Heinrich Heine University Düsseldorf replicates key aspects of the PDAC microenvironment, providing a powerful tool for preclinical identification of new drug candidates and potentially reducing reliance on animal testing. The results were recently published online in the journal Lab-on-a-chip.

A Biochip to Mimic the Complexity of PDAC

Dynamic42 has designed an advanced microfluidic biochip that accurately mimics the PDAC microenvironment. Unlike conventional 2D cultures, which are limited in their predictive value for drug testing by failing to replicate key aspects such as cell-cell communication, mechanical properties, and nutrient distribution, our model integrates tumor spheroids, endothelial cells, and immune components within a dynamic fluid system. The biochip is structured in two chambers with three vertically stacked channels each separated by porous membranes, enabling precise control over nutrient and drug administration while maintaining cell integrity.

Testing Drugs in a Realistic Tumor Model

Although recent advances in microfluidics have led to tumor-on-chip systems that enable 3D culture of different cell types under dynamic flow conditions and mimic real-life pharmacokinetics, many lack essential components such as immune and endothelial cells that are critical to understanding tumor behavior.

Our PDAC-on-chip model overcomes these problems by enabling controlled drug delivery as well as immune cell migration as it contains both multicellular tumor spheroids (MCTS) composed of PANC-1 tumor cells and pancreatic stellate cells (PSCs) and a layer of human umbilical vein endothelial cells (HUVECs). Despite the mechanical stress of continuous flow, the endothelial barrier remained intact, allowing drug delivery via the vascular layer.

This biochip is mimicking real-life pharmacokinetics more effectively than static models. The histone deacetylase inhibitor vorinostat (suberoylanilide hydroxamic (SAHA)) was used to validate the chip. The results showed a significant reduction in the viability of tumor spheroids while maintaining endothelial integrity. These results underline the potential of the biochip to evaluate cancer treatments with greater accuracy before they enter clinical trials.

Administration of the inhibitor vorinostat (SAHA) in the PDAC biochip model. (A) Investigation of the influence of increasing vorinostat concentrations on the vasculature integrity. VE-cadherin (green), von Willebrand factor (red) as marker of the endothelial cells, DAPI for staining the cell nuclei (blue). Shown as MIP of a Z-stack. Scale 200 μm. (B) Investigation of the viability of the 3D PDAC spheroids in the biochip in the presence of vorinostat after 72 h administration (with **** = p ≤ 0.0001). (C) Permeability assay of vascular (HUVEC) layer after treatment with vorinostat for 72 h. FITC dextran assay was performed to measure the barrier integrity of the vascular layer after 72 h treatment with 1.5, 2.5, or 3.5 μm vorinostat. FITC dextran solution was added into the top channel. After 1 h the leakage into the mid channel was determined via fluorescence measurement. (Reproduced from Ref. Deipenbrock 2025 et al. with permission from the Royal Society of Chemistry)

In addition, the system successfully detected the infiltration of immune cells: Perfused monocytes migrated through the endothelial layer into the tumor spheroids and differentiated into M2-polarized macrophages within 96 hours. This allows researchers to explore immune responses and test immunotherapeutic strategies in a controlled environment.

Minimizing Animal Testing Through Biochip Technology

The reliance on animal models in cancer research has been a longstanding issue due to ethical concerns and biological differences between species. The Dynamic42 PDAC-on-chip provides a viable alternative, offering a human-based model that more accurately represents tumor behavior and treatment responses.

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