Mitogen-activated protein kinase and Protein kinase B signaling pathways (MAPK and Akt pathways)

The Mitogen-activated protein kinase (MAPK) and Protein kinase B (Akt) signaling pathways are two primary intracellular cascades that govern essential cellular processes such as growth, proliferation, survival, and metabolic homeostasis [1][2]. The MAPK pathway, specifically the Ras-Raf-MEK-ERK axis, is a major transducer of extracellular growth factor signals to the nucleus, driving the cell cycle and differentiation [1]. The Akt pathway, often integrated into the PI3K/Akt/mTOR axis, serves as a critical survival signal that inhibits apoptosis and regulates protein synthesis and glucose uptake [3]. Dysregulation of these pathways, frequently caused by oncogenic mutations in upstream receptors or internal components like KRAS, BRAF, or PIK3CA, is a hallmark of many human cancers and contributes to therapeutic resistance [4]. Because these pathways exhibit significant crosstalk and can provide compensatory escape routes for one another, they are frequently targeted by small-molecule inhibitors in combination therapies to improve clinical outcomes in oncology [2][5]. (Sources: [1] Pearson G, et al. Endocrine Reviews 2001; [2] Santarpia L, et al. Expert Opin Ther Targets 2012; [3] Manning BD, Toker A. Cell 2017; [4] Yuan J, et al. J Hematol Oncol 2019; [5] FDA Prescribing Information for Mekinist and Truqap).

Other names

MAPK/Akt signalingRas-Raf-MEK-ERK and PI3K-Akt-mTOR pathwaysMitogen-activated protein kinase and Akt signaling pathwaysExtracellular signal-regulated kinase and Protein kinase B pathways

Inhibition of specific protein kinase activity (e.g., MEK, Akt, or PI3K) within the signaling cascades to prevent downstream phosphorylation of effector proteins and transcription factors.