EREG

Epiregulin (EREG), also known as epiregulin or EPR, is a member of the epidermal growth factor (EGF) family that binds to EGFR and ERBB4 receptors. It functions as a potent mitogen, regulating cell proliferation, differentiation, and tissue repair through activation of downstream pathways including MAPK/ERK and PI3K/AKT. EREG is notably involved in wound healing and epithelial-mesenchymal transition (EMT), with crosstalk to Wnt/β-catenin and TGF-β signaling. Its overexpression has been implicated in pathological processes such as tumor angiogenesis and stromal remodeling.
Dysregulation of EREG is associated with colorectal, breast, and pancreatic cancers, as well as inflammatory disorders like rheumatoid arthritis. Therapeutic strategies targeting EREG-mediated signaling include EGFR monoclonal antibodies (e.g., cetuximab) and small-molecule tyrosine kinase inhibitors (e.g., erlotinib), though resistance mechanisms remain a challenge. Recent preclinical studies explore bispecific antibodies and combination therapies with immune checkpoint inhibitors to enhance efficacy. EREG is also investigated as a predictive biomarker for anti-EGFR therapy response in KRAS wild-type malignancies.