Protein Kinase B and Extracellular Signal-Regulated Kinase signaling pathway (AKT/ERK)

The AKT/ERK signaling pathway refers to the integrated network and crosstalk between the PI3K/AKT/mTOR and the Ras/Raf/MEK/ERK (MAPK) cascades, which are the primary drivers of cellular growth, survival, and metabolism (Mendoza et al., 2011, Nature Reviews Molecular Cell Biology). These pathways integrate signals from cell surface receptors, such as receptor tyrosine kinases (RTKs), to regulate fundamental processes including cell cycle progression and protein synthesis (Saini et al., 2013, Science Signaling). In many malignancies, genetic alterations such as KRAS or PIK3CA mutations lead to constitutive activation of these pathways, driving tumor progression and therapeutic resistance (McCubrey et al., 2007, Leukemia). Because these pathways often exhibit reciprocal regulation—where inhibition of one leads to the compensatory activation of the other—they are frequently studied together in the context of dual-pathway inhibition (Carracedo et al., 2008, Journal of Clinical Investigation). Pharmacological targeting involves specific inhibitors of nodes like AKT (e.g., capivasertib) or MEK (e.g., trametinib), with clinical success often depending on the identification of specific genetic drivers. Monitoring the phosphorylation status of AKT and ERK serves as a critical biomarker for assessing pathway activity and drug target engagement in clinical trials.

Other names

PI3K/AKT and MAPK/ERK pathwaysAKT/ERK crosstalkRas/Raf/MEK/ERK and PI3K/AKT/mTOR pathwaysGrowth factor signaling network

Small-molecule inhibition of specific kinase components (e.g., AKT, MEK, or ERK) to prevent the phosphorylation of downstream substrates, thereby inhibiting signal transduction pathways essential for cell cycle progression and survival.