Targeting SHP2: Dual breakthroughs in colorectal cancer therapy–from signaling pathway modulation to immune microenvironment remodeling

Figure 1 SHP2 plays a dual regulatory role in the PI3K/AKT pathway. SHP2 activates the PI3K/AKT pathway, contributing to chemoresistance. SHP2 decreases ROS production and inhibits ferroptosis via the PI3K/BRD4/TFEB axis. SHP2 stimulates the Tie2-PI3K/AKT/mTOR signaling cascade to mediate vascular remodeling and colorectal cancer (CRC) metastasis. In diabetes-associated CRC, SHP2 knockdown suppresses PI3K-AKT phosphorylation, enhances invasiveness. Monotherapy targeting SHP2 triggers feedback activation of AKT, necessitating its combination with AKT inhibitors for effective blockade. SHP2 inhibitors suppress the PI3K/AKT pathway and cell proliferation. CRC: Colorectal cancer. Created with biogdp.com (Supplementary material).