Mitogen-activated protein kinase signaling pathway (RAS-MAPK) (RAS-MAPK)

The RAS-MAPK signaling axis is a central signal transduction pathway that regulates essential cellular processes such as growth, proliferation, and survival (Source: NIH/NCI). It operates through a highly conserved kinase cascade where activated Ras GTPases trigger the sequential phosphorylation of Raf, MEK, and ERK proteins (Source: PubMed, PMID: 30033358). Dysregulation of this pathway, often through gain-of-function mutations in KRAS or BRAF, is a major driver of oncogenesis in various malignancies, including melanoma and pancreatic cancer (Source: Nature Reviews Cancer). Therapeutic strategies targeting this axis include direct inhibitors of mutant KRAS, BRAF, and MEK, which have significantly improved outcomes in specific patient populations. However, the clinical utility of these drugs is often limited by the rapid emergence of resistance and off-target toxicities (Source: StatPearls). Beyond cancer, germline mutations in this pathway lead to a group of developmental disorders known as RASopathies, such as Noonan syndrome (Source: NIH). Monitoring biomarkers like KRAS or BRAF mutation status is essential for selecting patients likely to benefit from these targeted therapies. Ongoing research focuses on overcoming resistance through combination therapies and the development of next-generation inhibitors targeting ERK or multiple nodes simultaneously.

Other names

Ras-Raf-MEK-ERK pathwayMAPK/ERK pathwayMAPK signaling cascade

Small molecule inhibition of specific nodes within the cascade (e.g., KRAS, BRAF, MEK, or ERK) to block downstream signal transduction and inhibit tumor growth.