Protein-dynamic of MYC/MYCN complexes
MYC proteins interact with a variety of other proteins. Those interaction partners play a role in diverse processes. Therefore, by changing interaction partners MYC can regulate different processes. The aim of our studies is to investigate the protein dynamic of MYC complexes, identify vulnerabilities and exploit it for therapy.
Targeting transcription-replication conflicts in MYCN-driven neuroblastoma
MYC proteins are transcription factors that bind to active promoters and promote transcriptional elongation. In neuroblastoma, a solid tumor in childhood, expression of MYCN is deregulated in high risk patients. Despite multimodal therapies the outcome of those patients is very poor showing the urgent need for new therapy options.
We could show already that MYC-driven tumors are dependent on Aurora-A and a sensitive to Aurora-A inhibitors. Those inhibitors entered already clinical trials but they have a lot of side effects and patients eventually relapse. We want to exploit combination therapies with Aurora-A inhibitors. Understanding the mechanisms how combination therapy is affecting the tumor will show new and specific vulnerabilities for improving therapy of neuroblastoma.