Fig. 1

KRAS signaling pathway and relevant inhibitors of each node. After the activation of receptor tyrosine kinase, GRB2 combines with the guanine nucleotide exchange factor SOS and then interacts with KRAS protein that is attached to the cell membrane, thereby promoting KRAS activation. Intrinsic KRAS GTP-GDP cycling is regulated by GEFs and GAPs. Once KRAS is mutated, this cycle is disrupted, allowing mutant KRAS protein to accumulate in an active state and thereby persistently activating downstream MAPK and PI3K signaling cascade, resulting in cell proliferation and survival. Various KRAS inhibitors listed in the box were developed to target each node of the KRAS signaling pathway and then evaluated in preclinical or clinical studies. Created with BioRender.com