High-level transcription of oncogenes often is driven by enhancers and super-enhancers. This makes it strongly dependent on several conditions: (1) high levels of transcriptional co-activators (blue), (2) the 3D genome-mediated enhancer-promoter communications (gray), (3) the formation of phase-separated condensates (green), (4) chromatin-associated factors (chromatin remodelers, histone chaperones and histone-modifying enzymes; red), and (5) the loss of transcriptional repression (black). These dependencies make possible targeting oncogenes’ transcription with minimal effects on basal transcription.