Grünewald Lab

German Cancer Research Center

Baden-Württemberg (DE1) · Germany

ERC-funded
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ERC Consolidator Grant · 2023

Targeting the undruggable: Leveraging neomorphic DNA-binding preferences of chimeric fusion oncogenes to promote cancer suicide

Many aggressive cancers, such as pediatric high-risk Ewing sarcoma and alveolar rhabdomyosarcoma, are fueled by and addicted to chimeric oncogenic transcription factors (OTFs). So far, all attempts to suppress these potent OTFs largely failed, wherefore they are classified as undruggable. This proposal challenges this dogma with a novel strategy to leverage, rather than to suppress, the exquisite neomorphic DNA-binding preferences of OTFs to express therapeutic genes specifically in cancer cells. In pursuing three ambitious aims, this project goes far beyond an original proof-of-concept study in which we drove pediatric cancer cells in preclinical models into suicide (CANCER-HARAKIRI) via…

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