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

Figure 3 SHP2 modulates the RAS/ERK pathway. SHP2 binding to IL-22R1 activates ERK signaling, thereby facilitating MAPK signaling and promoting cell proliferation. MUC1-C interacts with SHP2, enhancing RTK-RAS/ERK signaling, thus making it a promising therapeutic target for BRAF^V600E-mutant CRC. SHP2 deficiency diminishes RAF/MEK/ERK phosphorylation in KRAS-mutant CRC cells. The SHP2 inhibitor PCC0208023 suppresses cell proliferation by inhibiting the RAS/MAPK pathway and exhibits tumor volume reduction in preclinical models. CRC: Colorectal cancer. Created with biogdp.com (Supplementary material).