MAP2K1 and colorectal cancer: On the basis of the known roles for MAPK, AKT, STAT3, and EGFR signaling in intrinsic and/or acquired resistance to targeted therapies and their relevance in colorectal cancer, we next evaluated whether combining AZ’1569 with either MEK1/2 inhibitor AZD6244, AKT inhibitor capivasertib, JAK/STAT inhibitors ruloxitinib/AZD1480 or EGFR inhibitor cetuximab could effectively suppress colorectal cancer cell viability (Fig. 2C and D; Supplementary Figs. S1C–S1H).