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

The Mitogen-Activated Protein Kinase (MAPK) signaling pathway is a vital intracellular cascade that transduces extracellular stimuli, such as growth factors and cytokines, into specific cellular responses including proliferation, survival, and differentiation [1, 5, 13]. The core of the pathway is organized into a three-tiered kinase module consisting of a MAP kinase kinase kinase (MAP3K/RAF), a MAP kinase kinase (MAP2K/MEK), and a terminal MAP kinase (MAPK/ERK) [3, 11, 16]. Dysregulation of this pathway, frequently driven by oncogenic mutations in RAS or BRAF, is a hallmark of numerous human malignancies, particularly melanoma, colorectal cancer, and non-small cell lung cancer [1, 7, 10]. Consequently, the pathway serves as a primary therapeutic node, with several classes of inhibitors targeting RAF and MEK approved for clinical use [1, 8]. Beyond oncology, the MAPK pathway is deeply involved in the regulation of inflammatory responses and neurodegenerative processes, making it a focus for drug development in conditions like rheumatoid arthritis and Alzheimer's disease [8, 9, 10]. However, the therapeutic utility of MAPK inhibition is often challenged by the rapid emergence of drug resistance mediated by complex compensatory feedback loops [1, 3, 11].

Other names

MAPK cascadeRas-Raf-MEK-ERK pathwayERK signaling pathwayMitogen-activated protein kinase pathwayStress-activated protein kinase pathway

Small molecule inhibition of specific kinase components (e.g., RAF or MEK) to block the phosphorylation cascade and prevent downstream signaling to the nucleus.