In this study, we identified E2F4, a key mechanistic component of the DREAM transcriptional repression complex, as an important regulator of CRC sensitivity to irinotecan (CPT-11), a derivative of camptothecin (CPT) and a key anti-tumor drug used as standard-of-care for metastatic CRC [16, 17]. This evidence concerns the gene E2F4 and colorectal carcinoma.