The activation of insulin/IGF-dependent pathways has been also identified as a critical step contributing to several mechanisms of CRC resistance to both conventional and targeted therapeutic agents, leading to increased PI3K/Akt signaling that hinders the apoptotic signals triggered by chemotherapeutic drugs and desensitizes CRC cells to the effect of anti-EGFR antibodies[52]. Here, INS is linked to colorectal carcinoma.