Although histone deacetylases (HDACs) are involved in the carcinogenesis of solid tumors and HDAC inhibitors (HDACi) have already proved their efficacy in clinical trials, isoenzyme specific functions are still ill defined. In this thesis a high expression of HDAC2 in vivo in human and murine pancreatic ductal adenocarcinomas (PDAC) was demonstrated, suggesting an important role of HDAC2 in the pathogenesis of PDAC. In pancreatic cancer cell lines a HDAC2 dependent signaling pathway was discovered which resulted in resistance towards the topoisomerase II inhibitor etoposide by repression of the BH3-only protein NOXA. Targeting HDAC2 by HDACi will therefore be a promising strategy to overcome therapeutic resistance of PDAC against DNA damage inducing chemotherapeutics.     «

Although histone deacetylases (HDACs) are involved in the carcinogenesis of solid tumors and HDAC inhibitors (HDACi) have already proved their efficacy in clinical trials, isoenzyme specific functions are still ill defined. In this thesis a high expression of HDAC2 in vivo in human and murine pancreatic ductal adenocarcinomas (PDAC) was demonstrated, suggesting an important role of HDAC2 in the pathogenesis of PDAC. In pancreatic cancer cell lines a HDAC2 dependent signaling pathway was discover...     »