We are trying to understand the response of cancer cells to chemotherapy. In particular, we are analyzing the impaired replication of DNA and the damage response that results from injury to DNA. Our focus is on the signaling cascades driven by DNA damage, and on the activation of the tumor suppressor p53. Technologies include the use of large scale siRNA transfection, followed by automated fluorescence microscopy, and the analysis of DNA replication by incorporation of artificial nucleosides. As a disease model, we are investigating the response of colorectal cancer to therapy. On top of classical, DNA damaging chemotherapeutics, we are evaluating other broadly acting, yet non-genotoxic drug candidates, e. g. inhibitors of histone deacetylases and heat shock proteins. On long term, we are aiming at improving the response of tumor cells to chemotherapy by combining traditional and targeted therapeutic approaches.