Despite the potent antitumor effects, the application of MMA for cancer treatment is still limited due to its narrow therapeutic window and profound hepatotoxicity, which is probably due to the off‐targets of MMA other than SP1.[35, 36, 37] Our findings indicate that combination treatment with MEK/ERK inhibitors and SP1 inhibitors could improve antitumor activity, constituting a new and promising strategy for CRC treatment. Here, SP1 is linked to colorectal carcinoma.