Cancer Drug Target Discovery
We focus on a better understanding of the mechanisms of cancer drug resistance and metastasis.
- Erik Danen
Under this theme we generally follow four approaches:
- Unraveling cancer drug resistance mechanisms. For sarcoma and triple negative breast cancer, large RNAi and drug screens have been performed to identify candidate mechanisms for drug resistance. Clinical relevance of identified pathways and candidate targets to break resistance is done together with hospitals. Such clinically relevant mechanisms and candidate targets and drugs to intervene are further unraveled in 3D in vitro and in vivo models.
- Discovery of metastasis promoting candidate drug targets. In a set of 2D cell migration assays that are amenable to high throughput microscopy screening using a large panel of human breast cancer cell lines, candidate target genes for interfering with tumor cell motility are identified. Clinical relevance of identified candidate targets in the context of metastasis is done together with hospitals. Clinically relevant candidate targets are further validated in 3D micro tissue models and ultimately in in vivo models for metastasis.
- Cell adhesion signaling: dynamics, migration, and metastasis. We have a long standing interest in understanding how interactions of cells with their natural environment – the extracellular matrix – control cell behavior. We study the receptors involved in this interaction and the associated signaling machinery that controls in a very dynamic fashion cytoskeletal organization and cell shape. We also study bidirectional force-transmission between cells and the extracellular matrix, which occurs at cell adhesions and which regulates various processes implicated in tumor progression such as differentiation, growth, invasion, and angiogenesis.
- Mathematical modelling of cancer progression-related processes. We make use of image-based data and develop computational models to understand tumor growth and metastasis and the role of the immune system in tumor destruction.
Migration genes identified in 2D cultures corroborated in 3D micro tissues and clinically related to metastasis