Rat sarcoma virus signaling pathway (RAS pathway)

The Rat sarcoma virus (RAS) signaling pathway is a fundamental signal transduction network that conveys extracellular signals from cell surface receptors to the nucleus to regulate cell growth, survival, and differentiation (Simanshu et al., 2017, Cell). The pathway is centered around RAS proteins (KRAS, HRAS, and NRAS), which function as molecular switches by cycling between an active GTP-bound state and an inactive GDP-bound state (NCI, 2023). Activation of RAS triggers the recruitment and sequential phosphorylation of the RAF, MEK, and ERK kinases, a cascade that ultimately modulates gene expression (Prior et al., 2020, Cancer Research). Aberrant activation of this pathway, primarily through somatic mutations in RAS genes, is a major driver in human oncogenesis, occurring in nearly one-third of all cancers, including high-prevalence malignancies like pancreatic and lung adenocarcinoma (PubMed, 2022). While historically difficult to target, the development of allele-specific inhibitors like sotorasib has revolutionized the treatment of RAS-mutant cancers (FDA, 2021). Current therapeutic approaches involve direct RAS inhibition, targeting downstream effectors, or combining pathway inhibitors to overcome adaptive resistance (Nature Reviews Drug Discovery, 2021).

Other names

MAPK/ERK pathwayRas-Raf-MEK-ERK pathwayMitogen-activated protein kinase pathwayRAS-MAPK pathway

Inhibition of specific nodes within the signaling cascade, such as the GTPase activity of mutant RAS proteins or the kinase activity of downstream effectors like RAF and MEK, to prevent oncogenic signal transmission.