Pancreatic ductal adenocarcinoma (PDAC) is the most common and deadliest form of pancreatic cancer. It is a devastating disease with a poor prognosis and increasing incidence. It is usually diagnosed too late. 90 percent of all pancreatic tumors are PDACs. The 5-year overall survival probability is only 13 percent.

A major cause of rapid disease progression is the presence of a highly fibrotic tumor microenvironment consisting mainly of cancer-associated fibroblasts and various immune cells, in particular tumor-associated macrophages.

The research team has developed a pancreatic tumor-on-a-chip model precisely to find a therapeutic approach here. It consists of a biochip platform into which PDAC spheroids, mini pancreatic tumors consisting of PANC-1 cells and pancreatic stellate cells, have been integrated. The tumors in the chip can also be equipped with immune cells (monocytes) via a layer of human umbilical vein endothelial cells.The administration of a drug approved by the American FDA was tested.The team observed a significant reduction in the viability of the mini-PDAC spheroids. In addition, the monocytes migrated through the endothelium into the spheroids and differentiated into macrophages, which further developed into the type 2 phenotype. Type 2 macrophages are primarily involved in anti-inflammatory responses and in the induction of healing processes^{(1, 2)}.

The authors write that the new pancreatic tumor-on-chip model is suitable for mimicking the microenvironment of PDAC. The model provided a first proof-of-concept for controlled drug delivery and immune cell infiltration.
It is very suitable for identifying promising new drug candidates, which could reduce the dependence on animal experiments.

Original publication:
Deipenbrock A, Wilmes BE, Sommermann T, Abdo N, Moustakas K, Raasch M, Rennert K, Teusch NE. (2025). Modeling of the multicellular tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC) on a fit-for-purpose biochip for preclinical drug discovery. Lab Chip. 2025 Feb 28. doi: 10.1039/d4lc01016g. Epub ahead of print. PMID: 40018951.

Further information (press release):
https://dynamic42.com/press-release-tumour-on-chip-model/

Additional information:
(1) Kzhyshkowska, J. (2008).The Role of Macrophages in Inflammation and Cancer: New Processes Mediated by Stabilin-1
The Role of Macrophages in Inflammation and Cancer: New Processes Mediated by Stabilin-1.
Act Dermatol 2008; 34: 72-84. DOI 10.1055/s-2007-995658
(2) Michael Orth; Philipp Metzger; Sabine Gerum; Julia Mayerle; Günter Schneider; Claus Belka; Maximilian Schnurr; Kirsten Lauber (2019).Ductal adenocarcinoma of the pancreas: biological features, state of the art and outlook on multimodal treatment approaches of the future.Compass Oncol 6 (4): 196-208. https://doi.org/10.1159/000504640