The role of chromosome topology in MYCN function and neuroblastoma evolution and its potential for clinical exploitation (B01)

• Subject Area: Cell Biology ; Hematology, Oncology
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 493872418

The project aims to test the dependence of MYCN-amplified NB growth and evolutionary chemoresistance on the function of TFIIIC and the exosome complex. To this end, TFIIIC is knocked down by shRNA in a transgenic mouse model and the structural subunit of the exosome complex, EXOSC5, is decimated by an auxin-inducible degron in an orthotopic mouse transplantation model. The TFIIIC/AURKA balance is also disrupted by PROTAC-mediated AURKA degradation. This is a first step towards clinical use for the treatment of patients with relapsed MYCN-amplified NB.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1588: Decoding and Targeting Mechanisms of Neuroblastoma Evolution
• Applicant Institution: shared FU Berlin and HU Berlin through:; Charité - Universitätsmedizin Berlin
• Project Heads: Professor Dr. Martin Eilers; Dr. Dimitrios Papadopoulos