Abstract

Epithelial tissues maintain homeostasis by employing sophisticated mechanisms to promote clearance of precancerous cells, thus preventing tumorigenesis. Two key processes—cell competition and extrusion—collectively termed epithelial defense against cancer (EDAC), enable normal epithelial cells to outcompete or physically expel transformed counterparts. This review integrates recent advances in EDAC, detailing critical proteins, biomechanical cues, and their interplay with immune surveillance. We quantify cellular proportions essential for EDAC efficacy and examine cancer models, focusing on pancreatic, colorectal, and mammary cancers. By linking molecular mechanisms to clinical potential, we position EDAC as a promising frontier for cancer prevention and therapy. © The Author(s) 2025.