TNF and cancer: For example, the EGFR signaling pathway is a crucial oncogenic driver and an upstream regulator of the Ras/rapidly accelerated fibrosarcoma 1/MEK/MAPK pathway.[36] TNF can activate the AKT signaling pathway via phosphatidylinositol 3-kinase (PI3-K) and inhibit cytochrome C release in mitochondria-dependent apoptosis.[37] HIF-1 acts as a signaling hub that coordinates the activities of multiple transcription factors and signaling molecules that influence tumorigenesis.[38] Furthermore, PD-L1 is frequently overexpressed in human cancers.