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

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