Concerning that the activation of the AKT pathway is usually associated with drug resistance (Datta et al., 2017; Song et al., 2017; Vitiello et al., 2019), we propose that the blockage of the reactivation of the AKT pathway in response to SHP2 inhibition may overcome the resistance of CRC cells to SHP2 inhibitors (Song et al., 2017; Sun et al., 2019; Leung et al., 2020). This evidence concerns the gene AKT1 and colorectal carcinoma.