Targeting the roots of cancer metastasis and therapy resistance

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Despite great progress in the last two decades, cancer is still an often deadly disease. Even today only about 30% of cancer patients, who received modern treatment regimens including targeted drugs and immunotherapy respond with long-term remission. The most fatal steps in cancer are metastasis, which is responsible for >90% of cancer-associated death, and therapy resistance. These facts demonstrate the high pressure to develop novel therapeutic strategies. My research over the last 20 years contributed to conceptual advance and the identification of novel molecular links in tumor progression towards metastasis and therapy resistance. The work of my and other groups demonstrated that a fraction of cancer cells within a heterogenous tumor is responsible for metastasis, therapy resistance and disease relapse. These cancer cells are highly plastic and transiently activate the embryonic embryonic EMT (epithelial-mesenchymal transition)-program. The goal of the proposed project is to molecularly characterize this until now “untargetable” fraction of highly plastic cancer cells, thereby supporting the development of novel therapeutic strategies against therapy resistance and metastasis.