Pancreatic cancer has a very poor prognosis and rapidly develops resistance to standard chemotherapy. This resistance is linked to the activation of an epithelial-mesenchymal transition (EMT) and is conferred by expression of the EMT activator ZEB1 and subsequent transcriptional repression of its target genes miR-200. We shall identify epigenetic modifications on miR-200 and other ZEB1 target genes and reactivate their endogenous expression by epigenetic drugs. The aim is to thereby restore chemo-sensitivity and to allow treatment of pancreatic cancers with combined epigenetic and standard therapy.
- Meidhof S., Brabletz S., Lehmann W., Preca B.T., Mock K., Ruh M., Schuler J., Berthold M., Weber A., Burk U., Lubbert M., Puhr M., Culig Z., Wellner U., Keck T., Bronsert P., Kusters S., Hopt U.T., Stemmler M.P. and Brabletz T. (2015) ZEB1-associated drug resistance in cancer cells is reversed by the class I HDAC inhibitor mocetinostat. EMBO Mol Med 7, 831-847.