Drug Resistance; Fibroblast Growth Factors
Our research is focused on growth factors and their receptors involved in cancer cell growth and drug resistance. We aim to (1.) understand how growth factor signals contribute to malignancy (2.) translate this knowledge into strategies for therapeutic interventions and (3.) characterize the mechanisms that determine sensitivity or resistance of tumors to molecularly targeted therapeutics.
Within this area we are interested on the one hand in receptor tyrosine kinases (RTKs) of the fibroblast growth factor receptor (FGFR) and epidermal growth factor recetor (EGFR, erbb) families which are (over)activated in many human cancer types and on the other hand in activins. The latter are cytokines of the transforming growth factor (TGF) beta family and act as regulators of cell differentiation and cell death in a tissue-specific manner. Their activity is stringently controlled by antagonistic follistatin proteins.
Techniques, methods & infrastructure
A broad spectrum of biochemical, cell biological, and imaging techniques are used including optically controlled receptor tyrosine kinases (Opto-RTKs) co-developed in our group.
- Schelch, K. et al., 2014. Fibroblast Growth Factor Receptor Inhibition Is Active against Mesothelioma and Synergizes with Radio- and Chemotherapy. American Journal of Respiratory and Critical Care Medicine, 190(7), pp.763-772. Available at: http://dx.doi.org/10.1164/rccm.201404-0658OC.
- Grusch, M. et al., 2014. Spatio-temporally precise activation of engineered receptor tyrosine kinases by light. The EMBO Journal, 33(15), pp.1713-1726. Available at: http://dx.doi.org/10.15252/embj.201387695.
- Hoda, M.A. et al., 2012. Suppression of activin A signals inhibits growth of malignant pleural mesothelioma cells. British Journal of Cancer, 107(12), pp.1978-1986. Available at: http://dx.doi.org/10.1038/bjc.2012.519.
- Metzner, T. et al., 2011. Fibroblast Growth Factor Receptors as Therapeutic Targets in Human Melanoma: Synergism with BRAF Inhibition. Journal of Investigative Dermatology, 131(10), pp.2087-2095. Available at: http://dx.doi.org/10.1038/jid.2011.177.
- Grusch, M. et al., 2006. Deregulation of the activin/follistatin system in hepatocarcinogenesis. Journal of Hepatology, 45(5), pp.673-680. Available at: http://dx.doi.org/10.1016/j.jhep.2006.06.014.