Finally, we tested whether E2F4 knock-down, despite not directly impacting the tumorigenic capacity of CRC cells, would nonetheless render them more vulnerable to in vivo chemotherapy with irinotecan, administered according to the same dosing regimen that we used to investigate drug-induced transcriptional perturbations and designed to approximate the dosing regimens used in human patients (Figure 1A–B). Here, E2F4 is linked to colorectal carcinoma.