A major pathomechanism and obstacle for the treatment of malignant disease is resistance of tumor cells against apoptosis and chemotherapy. We hypothesize that a) cell-intrinsic as well as cell-extrinsic mechanisms mediated by the microenvironment and the functional interplay of these pathways contributes to escape from cell death and to drug resistance, and b) that these mechanisms reflect specific vulnerabilities of tumor cells that can be therapeutically targeted. In order to understand the molecular mechanisms of resistance and translate them into novel treatment strategies, we initiated this Helmholtz Virtual Institute with the aim of "Understanding and Overcoming Resistance to Apoptosis and Therapy in Leukemia".

We will use chronic lymphocytic leukemia (CLL) –the most common adult leukemia in the western world- as an ideally suited model system, but expect to identify general mechanisms contributing to cancer cell resistance.