Despite the common use of 5-FU-based therapies for CRC BM, resistance often arises,3 partly due to the WNT/β-catenin pathway activation.30 Given our data implicating IRS2 in β-catenin activation in CRC cells, we hypothesized that inhibiting IRS2 might enhance CRC cells sensitivity to 5-FU. Here, IRS2 is linked to colorectal carcinoma.