Epidermal growth factor receptor–STAT3 signaling pathway (EGFR-STAT3 pathway)

The **Epidermal growth factor receptor–STAT3 pathway** is a signal transduction cascade in which EGFR, a receptor tyrosine kinase, activates downstream effectors such as STAT3. EGFR activation by ligand binding leads to its autophosphorylation and recruitment of signaling proteins, including STAT3, which can be phosphorylated directly or via intermediate kinases (e.g., JAKs), leading to STAT3 dimerization, nuclear translocation, and gene transcription. This pathway is frequently dysregulated in cancers, promoting cell proliferation, survival, immune evasion (including upregulation of PD-L1), and tumorigenesis. Both EGFR and STAT3 are validated therapeutic targets, and their co-activation underlies resistance to targeted therapies, prompting interest in pathway co-inhibition and combination therapeutic approaches to improve efficacy.

Other names

ErbB-1HER1STAT-3EGFR–STAT3 pathwayEGFR–JAK–STAT3 pathwayEGF–STAT3 signaling

Inhibition of the EGFR–STAT3 pathway involves targeting EGFR activity (e.g., blocking tyrosine kinase, dimerization, or ligand binding) and/or STAT3 activity (e.g., inhibiting its phosphorylation, dimerization, or DNA binding). Combination approaches aim to simultaneously block these interconnected nodes to overcome resistance and synergistically inhibit signaling and proliferation.