Targeting MYCN-dependent resolution of transcription-replication conflicts (B02)

• Subject Area: Biochemistry ; Hematology, Oncology ; Pediatric and Adolescent Medicine
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 493872418

This project investigates the identification of synergistic drug combinations by specific CDK12 inhibitors that trigger transcription-replication conflicts. The MYCN-AURKA-CDK12 axis will be characterized in vitro and in vivo and genetic and non-genetic resistance mechanisms will be investigated. Heterogeneity of ecDNA copy number in NBs will be investigated to understand how it affects MYCN levels and MYCN-related transcription-replication conflicts. Changes in the differentiation state and tumor immune microenvironment during treatment will also be investigated to highlight potential time windows of increased susceptibility to immunotherapy.

• 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: Professorin Dr. Gabriele Büchel; Professor Dr. Anton Henssen