Mitogen-activated protein kinase and Phosphoinositide 3-kinase-Akt signaling pathways (MAPK and PI3K-Akt pathways)

The Mitogen-activated protein kinase (MAPK) and Phosphoinositide 3-kinase (PI3K)-Akt signaling pathways are two of the most critical intracellular signaling networks regulating essential cellular processes such as growth, proliferation, survival, and metabolism (StatPearls, NBK557531). The MAPK pathway typically involves a cascade of protein kinases (RAS-RAF-MEK-ERK) that transmit signals from surface receptors to the nucleus to regulate gene expression (PubMed, 25766570). The PI3K-Akt pathway is primarily activated by growth factors and regulates glucose metabolism and protein synthesis through downstream effectors like mTOR (Nature Reviews Cancer, 10.1038/nrc.2017.26). Dysregulation of these pathways, often through mutations in genes like BRAF, KRAS, or PIK3CA, is a hallmark of many cancers, leading to uncontrolled cell division and resistance to apoptosis (NIH, PMC3662466). Consequently, these pathways are major focuses of oncology drug development, with numerous inhibitors targeting specific kinases within the cascades. However, therapeutic efficacy is often limited by complex crosstalk between the two pathways, where inhibition of one can lead to compensatory activation of the other (PubMed, 23665268).

Other names

RAS-RAF-MEK-ERK pathwayPI3K-Akt-mTOR pathwayMAPK/ERK pathwayPI3K/Akt pathwayGrowth factor signaling cascades

Inhibition of specific kinase components within the cascades, such as BRAF, MEK, PI3K, or mTOR, to block downstream signaling that promotes tumor growth and survival (StatPearls, NBK557531; Nature Reviews Cancer, 10.1038/nrc.2017.26).