Transcription inhibitors affect differentially regulatory sequences of genes and trigger cell death in cancer cells. A) Transcription inhibitors differentially affect the regulatory sequences of genes and trigger cell death in cancer cells. This fact is related to requirement of transcription factors or coactivators recruited on regulatory sequences such as enhancers and promoters. Typical enhancers recruit several transcription factors and coactivators in order to enhance transcription of downstream gene; however, super-enhancer needs an excess of transcription than a typical enhancer, rendering the gene very sensitive to transcription perturbation. Similarly, transgene overexpression (whose promoter contain specific sequences for transactivators or specific cis elements), has been demonstrated to be affected by transcription inhibitors o genetic deficient in transcription [94, 95]. In all cases, the final result is the depletion of messenger RNAs mainly genes that showed a high level of expression such as oncogenes. B) Cancer cells are more sensitive to suffer cell death after exposition to transcription inhibitors compared with normal cells. As we have seen before, transcription inhibitors cause a depletion of messenger RNAs mainly oncogenes and overexpressed genes; however, because cancer cells are oncogene-dependent for survival, their depletion triggers cell death preferentially in cancer cells, while preserving normal cells. This principle represents a strategic point for designing drug that targets directly cancer cells.