The small molecular inhibitor AZA197 has been used to inhibit Cdc42 in the treatment of KRAS mutant colorectal cancers. There was evidence that Cdc42 inhibition by AZA197 treatment suppresses proliferative and pro-survival signaling pathways via PAK1-ERK signaling and reduces colon cancer cell migration and invasion. In mice, systemic AZA197 treatment in vivo reduced primary tumor growth and prolonged survival. Therapy targeting Rho GTPase Cdc42 signaling pathways may be effective for treatment of patients with advanced colon cancer overexpressing Cdc42, and particularly those with KRAS-mutant disease.