Prof. Dr. Barbara Grüner

Emmy Noether Group
Molecular Tumorpathology
Department of Medical Oncology

University Hospital Essen

Phone: +49 201 723 8142
Email

Metastasis represents a major clinical challenge that is driven by an as of yet poorly understood switch in cell state. Without acquiring additional genetic alterations, a cancer cell can switch from an immotile cell growing in a cluster to a motile, selfcontained cancer cell that can home at a secondary site and re-start proliferation. We recently developed a multiplexed small molecule screening platform that allows interrogating small molecules in vivo in an efficient high-throughput manner for their effect on cancer metastasis. This approach integrates molecular cell barcoding, in vitro compound pretreatment, and in vivo selection to allow multiplexed compound screening in mice. We have successfully applied this platform and identified key compounds that act in cellular signalling and in lipid metabolism as inhibitors of metastatic ability in pancreatic ductal adenocarcinoma (PDAC). Within the CRC, we will functionally characterize the exact mechanisms with which these compounds regulate the metastatic cell switch in PDAC. We will identify and validate their cellular targets using in vitro and in vivo preclinical model systems and provide insight into the mechanisms by which the cellular targets of our key compounds promote the metastatic cell state. This will in turn provide us with novel characteristics and targetable pathways for this highly important cell state.