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SFB 1709:  Cellular Plasticity in Myeloid Malignancies: From Mechanisms to Therapies

Subject Area Medicine
Term since 2025
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Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 533056198
 
Cancer cells are in a constant state of molecular flux, starting during their pre-malignant evolution from normal tissues, through disease progression, therapy-induced remission and eventual relapse. While this metastable behavior can be partially explained by the progressive acquisition of oncogenic driver mutations within the genome, it is increasingly apparent that cancer cells exist in a plastic state, in which the erosion of molecular mechanisms that enforce normal cellular identity and function occurs through non-genetic means. This cellular plasticity underlies the capacity of cancer cells to dynamically adapt and propagate in the face of diverse environmental challenges. In this CRC, we will focus on myeloid malignancies as a model to dissect the various molecular mechanisms that enable and regulate cancer cell plasticity. We will explore the biological consequences resulting from different forms of plasticity and will leverage this knowledge towards the identification of novel therapeutic strategies which either restrict plasticity or exploit synthetic vulnerabilities that are associated with this state. To these ends, the CRC brings together both basic and clinical research partners in a novel constellation, enabling a research program encompassing several myeloid malignancies, which will be studied across a range of clinically-relevant settings that necessitate phenotypic plasticity to facilitate cancer propagation. A central tenet of the research consortium is that it will effectively leverage the multidisciplinary expertise of the members, along with the array of cutting-edge technologies at their disposal, to comprehensively interrogate the phenomenon of cancer cell plasticity to a degree which would be impossible for any individual group member. Effective sharing and integration of experimental resources and data will enable the group to identify the common fundamental molecular and biological features that span the myeloid diseases and processes studied, as well as those that are context specific. This program will provide novel insights into the underlying etiology of cancer cell plasticity that we envisage will hold relevance beyond the sphere of hematologic malignancies, and will pave the way for new therapies which tackle this unmet clinical problem.
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