ErbB signaling network (ErbB/MAPK/PI3K)

The ErbB signaling network is a complex system of intracellular pathways initiated by the ErbB family of receptor tyrosine kinases, which includes EGFR (ErbB1), HER2 (ErbB2), HER3 (ErbB3), and HER4 (ErbB4) [Yarden & Sliwkowski, 2001, Nature Reviews Molecular Cell Biology]. Upon ligand binding or receptor dimerization, these receptors activate two primary downstream cascades: the Mitogen-Activated Protein Kinase (MAPK) pathway and the Phosphoinositide 3-kinase (PI3K)-Akt pathway [Wee & Wang, 2017, Cancers]. The MAPK pathway (Ras-Raf-MEK-ERK) is a central regulator of cell cycle progression and proliferation, while the PI3K-Akt-mTOR pathway primarily governs cell survival, growth, and metabolism [Manning & Toker, 2017, Cell]. Dysregulation of this network, through gene amplification, overexpression, or activating mutations, is a major driver in various malignancies, including breast, lung, and colorectal cancers [Hynes & Lane, 2005, Nature Reviews Cancer]. Therapeutic strategies targeting this network include monoclonal antibodies that block extracellular receptor domains and small-molecule tyrosine kinase inhibitors (TKIs) that prevent intracellular signaling, making it one of the most successful areas of targeted oncology therapy [Appert-Collin et al., 2015, Frontiers in Pharmacology].

Other names

HER signaling pathwayRas-Raf-MEK-ERK and PI3K-Akt-mTOR pathwaysEpidermal growth factor receptor signalingMAPK signaling pathwayPI3K-Akt signaling pathway

Inhibition of receptor tyrosine kinase activity, blockade of ligand binding, or inhibition of downstream intracellular kinases (e.g., MEK, PI3K, mTOR) to disrupt signaling cascades [Hynes & Lane, 2005, Nature Reviews Cancer].