Epidermal growth factor receptor and Nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathways (EGFR and NF-κB pathways)

The Epidermal Growth Factor Receptor (EGFR) and Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathways are two interconnected regulatory networks that play pivotal roles in cell growth, survival, and immune responses (UniProt: P00533; NCBI: 4790). EGFR is a cell-surface receptor tyrosine kinase that, when activated by ligands like EGF or TGF-alpha, triggers intracellular cascades such as the PI3K/Akt and MAPK/ERK pathways. These cascades often converge on the NF-κB complex, a master transcription factor that translocates into the nucleus to promote the expression of genes involved in anti-apoptosis and inflammation (Shostak & Chariot, 2015). In various malignancies, including non-small cell lung cancer (NSCLC) and head and neck squamous cell carcinoma, the aberrant activation of both pathways creates a synergistic effect that drives tumor aggressiveness and resistance to standard treatments (Bivona et al., 2011). Therapeutic strategies often involve EGFR inhibitors; however, the activation of NF-κB is a recognized mechanism of acquired resistance, leading to investigations into dual-inhibition approaches to improve clinical efficacy. This entry is marked as incorrect because it describes a complex interaction between two distinct pathways rather than a single therapeutic target molecule.

Other names

EGFR/NF-κB crosstalkEGFR-NF-kappaB axisEpidermal growth factor receptor and Nuclear factor-kappa B signalingEGFR-IKK-NF-kappaB pathway

Drugs targeting these pathways function by inhibiting the tyrosine kinase activity of EGFR (e.g., TKIs), blocking ligand binding to the extracellular domain of EGFR (e.g., monoclonal antibodies), or inhibiting the proteasomal degradation of IκB to prevent the nuclear translocation of NF-κB transcription factors.