Organ on chip

Research projects

Metastatic-on-Chip Model

Cancer cells located within a microvasculature network. Top row: Holoclones remain within the endothelial lining marked by PECAM1 (left), whereas paraclones extravasate in the surrounding matrix (right). PECAM1 = red, A549 subclones = green. Bottom row: 3D surface rendering illustrates the different extravasation dynamics of both A549 subclones. Scale bar = 20 µm.

Gruppe Guenat   The Metastasis-on-Chip project aims to replicate the metastatic process, focusing specifically on extravasation and colony formation. Our initial studies evaluate the metastatic potential of cancer cells based on their phenotypes, using the A549 non-small cell lung cancer (NSCLC) cell line, which exhibits distinct phenotypic variations. We discovered that paraclones, characterized by a mesenchymal phenotype, successfully extravasate, while holoclones, with an epithelial phenotype, do not. Additionally, paraclones demonstrated significantly greater migratory behavior compared to holoclones. These findings provide valuable insights into the mechanisms of metastasis and lay the groundwork for further exploration of targeted therapies.

 

Targeting cellular metabolism to augment cancer therapy

Inhibition of lactate metabolism selectively damages the mitochondria of cancer cells, and when combined with radiotherapy, leads to a marked reduction in tumor growth in a mouse model of NSCLC – Reference source: Deng H. et al., 2025 (https://www.nature.com/articles/s41467-025-57906-3)

Marti Group. PD Dr. med. Thomas Marti

The aim of this project is to investigate how the nucleotide/lactate metabolism and the DNA damage response machinery are associated with the tumor initiating capacity, the chemotherapy response, and the metastatic capacity of lung and mesothelioma cancer stem cells. In addition, we are exploiting treatment induced cellular adaptations as novel targets for cancer therapy.