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Molecular mechanisms of programmed cell death (apoptosis) and the development of apoptosis resistance in tumors


Cancer is still one of the most common causes of death in Europe and any treatments to avoid or alleviate health risk associated with cancer bears the potential to significantly ameliorate the health of the European population. A major rationale in current cancer therapy is based on the understanding that virtually all cells in higher organisms posses a cellular suicide program referred to as apoptosis. Under physiological circumstances, apoptosis is induced as a developmental program or, more frequently, as a consequence of environmental insult. In the latter instance, apoptosis is probably the single most important tumor suppressor mechanism in mammals. Cancer therapy has long relied on empirically derived cytotoxic treatments that are now recognized as relatively unspecific ways to induce cell death, with a certain preference for cancer cells and rapidly proliferating cells. A major clinical problem, of considerable practical importance, is the development of resistance to cytotoxic cancer drugs. From our current perspective, resistance to cytotoxic cancer drugs can be largely explained by the development of resistance to apoptosis. To resolve this problem, the project will study the following key questions:
1. What determines the selective apoptotic killing of tumor cells by anticancer agents?
2. Which molecular alterations underlie the development of apoptosis resistance in tumor cells and how can these alterations be reversed by specific treatments? In order to develop new strategies for the diagnosis and new therapeutic approaches for the treatment of apoptosis-resistant tumors, the pathways triggering apoptosis in various cell types will be addressed by a detailed analysis of the signaling pathways in various human tissues. We also propose to study the role of various cellular genes and mutations in these genes for the execution of the apoptotic response. A particular aspect of the current program is the use of genome-wide approaches


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NET - Research network contracts


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Rennweg 10

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Participants (5)