Cyclooxygenase-2–Epidermal Growth Factor Receptor signaling network (COX-2–EGFR network)

The Cyclooxygenase-2–Epidermal Growth Factor Receptor (COX-2–EGFR) signaling network is a critical regulatory axis involved in the progression of various epithelial malignancies (PMID: 15548688). This network functions through a bidirectional crosstalk where COX-2-derived Prostaglandin E2 (PGE2) triggers the transactivation of EGFR, while EGFR signaling simultaneously upregulates COX-2 expression (PMID: 11544177). This reciprocal activation stimulates downstream pathways such as PI3K/Akt and MAPK/ERK, which collectively promote cell survival, proliferation, and angiogenesis while suppressing apoptosis (PMID: 12855634). In clinical settings, this network is a significant driver of resistance to EGFR-targeted therapies, as COX-2 activity can provide alternative survival signals (PMID: 19147753). Consequently, pharmacological strategies often employ a combination of COX-2 inhibitors, like celecoxib, and EGFR inhibitors, such as erlotinib or cetuximab, to achieve synergistic anti-tumor effects (PMID: 16322275). This dual-targeting approach aims to disrupt the feedback loop and enhance the efficacy of treatment in cancers of the colon, lung, and head and neck (PMID: 15150108).

Other names

COX-2/EGFR axisPTGS2-EGFR crosstalkProstaglandin E2-EGFR signaling pathwayCOX-2–EGFR–downstream signaling pathway

Dual inhibition of the Cyclooxygenase-2 enzyme and the Epidermal Growth Factor Receptor tyrosine kinase to disrupt synergistic pro-survival signaling and overcome acquired resistance (PMID: 15548688).