Ras-extracellular signal-regulated kinase mitogen-activated protein kinase pathway (Ras-ERK MAPK pathway)

The Ras-ERK MAPK pathway is a fundamental signal transduction cascade that conveys extracellular signals from receptor tyrosine kinases to the nucleus to regulate gene expression. The pathway is characterized by a core kinase architecture where activated Ras GTPases recruit and activate Raf (MAPKKK), which phosphorylates MEK (MAPKK), which in turn phosphorylates and activates ERK (MAPK) (Source: StatPearls, MAPK Signaling Pathway, 2023). This cascade is a central regulator of cell proliferation, differentiation, and survival across various tissue types (Source: NIH, National Cancer Institute). Hyperactivation of this pathway is one of the most frequent drivers of human oncogenesis, often resulting from gain-of-function mutations in KRAS or BRAF (Source: Nature Reviews Cancer, 2020). Because of its pivotal role in tumor growth, the pathway is a primary focus of precision oncology, with numerous FDA-approved inhibitors targeting specific nodes like BRAF and MEK. However, therapeutic efficacy is often limited by the rapid development of drug resistance through compensatory feedback loops or secondary mutations, necessitating the use of combination therapies (Source: PubMed, PMC7075144).

Other names

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

Inhibition of specific components within the signaling cascade (such as KRAS, BRAF, or MEK) to block downstream phosphorylation of ERK and subsequent transcription of genes involved in cell cycle progression and survival.