Mitogen-activated protein kinase (MAPK) and AKT signaling pathways (MAPK/AKT)

The MAPK/AKT signaling pathways are two interconnected intracellular networks that govern essential cellular processes such as growth, proliferation, survival, and metabolism (StatPearls, 2023). The MAPK pathway, specifically the Ras-Raf-MEK-ERK cascade, is primarily involved in transmitting signals from cell surface receptors to the nucleus to regulate gene expression and the cell cycle (NIH, 2023). In parallel, the AKT pathway (PI3K/AKT/mTOR) acts as a master regulator of cell survival and metabolic homeostasis, responding to insulin and growth factor stimulation (UniProt, 2024). Dysregulation of these pathways is a hallmark of human oncogenesis, frequently driven by mutations in genes like KRAS, BRAF, and PIK3CA, which lead to constitutive activation and uncontrolled cell growth (PubMed, 2022). While numerous targeted therapies exist to inhibit specific nodes within these pathways, such as MEK or PI3K inhibitors, the extensive crosstalk and feedback loops between them often result in compensatory activation and therapeutic resistance (Trends in Cell Biology, 2011). These pathways are also implicated in non-oncogenic conditions, including metabolic disorders like type 2 diabetes and various neurodegenerative diseases (Nature Reviews, 2020). Therapeutic strategies often involve dual inhibition to prevent the bypass mechanisms that occur when only one pathway is targeted (Cancer Discovery, 2019). Monitoring biomarkers like phospho-ERK and phospho-AKT is crucial for assessing the efficacy of these inhibitors in clinical settings (Journal of Clinical Oncology, 2021).

Other names

Ras-Raf-MEK-ERK and PI3K-AKT-mTOR pathwaysMAPK/ERK and PI3K/AKT signalingGrowth factor signaling pathwaysMAPK/AKT axis

Inhibition of specific kinase components within the MAPK or AKT cascades to disrupt downstream signaling and inhibit cellular processes like proliferation and survival.