Oncogenic activation of MYC transcription factors is one of the most common genetic events observed in cancer genomes. Despite early discovery of MYC oncogenic activities, > 30 years of research have failed to identify clinically effective compounds capable of directly inhibiting MYC activity. MYC is considered to be undruggable. However, direct MYC targeting can be by-passed through pharmacological inhibition of its regulatory partners or target genes. Within the DKTK JF project “Therapeutic targeting of Myc”, we successfully established a MYC targeting pipeline for efficient pre-clinical drug testing and drug development filling an important gap between molecular target identification and clinical trials. Results from this project show that targeting epigenetic proteins including histone deacetylases (HDACs) and BET proteins as well as regulators of MYC family transcript and protein stability via aurora kinase A (AURKA) are among the most promising (combination) strategies for indirect MYC inhibition. Based on the results of this project the new INFORM2 clinical phase I/II trial “INFORM2-NivEnt” (IIT) was  initiated in July 2019.