TNF and cancer: Furthermore, extracellular-regulated kinase (ERK) and tumor necrosis factor (TNF) are the two main signaling pathways involved in intracellular signaling [12], and a recent study demonstrated that CREPT acts as an intrinsic mediator in field cancerization, facilitating the transition of normal epithelial cells toward a malignant phenotype under the influence of the tumor microenvironment, particularly through the action of cancer-derived small extracellular vesicles (CDEs) and the activation of signaling pathways like ERK and TNF.