Neuroendocrine tumors like childhood neuroblastoma can be driven by amplification of MYCN. For protection of degradation by the proteasome system MYCN is stabilized by Aurora-A. MYCN also forms complexes with TFIIIC, RAD21 and TOP2A. This newly discovered complex is required for MYCN-dependent pause release of RNA Polymerase II (RNAPII). During S-phase Aurora-A displaces the MYCN/TFIIIC complex, inhibits pause release of RNAPII and consecutively prevents replication/transcription conflicts. The MYCN/Aurora-A complex can be disrupted by small molecules like MLN8237 and treatment with those inhibitors shows therapeutical efficacy in human neuroblastoma. We hypothesize that MYC-driven tumors are dependent on Aurora-A to avoid replication/transcription conflicts. We therefore work on improving therapeutic strategies using Aurora-A inhibitors in combination with inhibitors targeting different enzymes of the replication or transcription machinery.