Mitogen-activated protein kinase signaling pathway (Ras-Raf-MEK-ERK cascade) (MAPK pathway)

The Ras-Raf-MEK-ERK pathway is a central mitogen-activated protein kinase (MAPK) signaling cascade that communicates signals from surface receptors to the nucleus to regulate gene expression and cellular activity [1][2]. The pathway is activated by various extracellular stimuli, such as growth factors, which trigger the activation of the small GTPase Ras; Ras then recruits and activates Raf kinases (MAP3Ks), which in turn phosphorylate and activate MEK1/2 (MAP2Ks), ultimately leading to the activation of ERK1/2 (MAPKs) [3][4]. Dysregulation of this pathway, frequently caused by gain-of-function mutations in KRAS, NRAS, or BRAF, is a primary driver of oncogenesis in approximately 30% of human cancers, including melanoma, pancreatic, and lung adenocarcinomas [5]. Therapeutic interventions often focus on targeting specific mutated nodes within the cascade, such as BRAF or MEK, to halt pathological cell proliferation [6]. However, the therapeutic efficacy is often limited by complex feedback mechanisms and the rapid emergence of resistance through alternative signaling routes [7].

Other names

Ras/Raf/MAPK pathwayERK signaling pathwayMAPK/ERK cascadeRas-Raf-MEK-ERK signalingExtracellular signal-regulated kinase pathway

Small molecule inhibition of specific cascade nodes, including BRAF, MEK1/2, or mutant KRAS, to prevent the sequential phosphorylation and activation of downstream effectors that drive oncogenic growth and survival.