EGFR associated signaling pathways in lung cancer. Phosphorylation, i.e. activation of the Epidermal Growth Factor Receptor (EGFR) results in various downstream signaling pathways including the JAK-STAT-signaling, KRAS, MAPK and the phosphatidylinositol 3-kinase (PI3K) related pathway. Extrinsic binding of the Endothelian Growth Factor (EGF) to the corresponding Endothelian Growth Factor Receptor (EGFR) leads to phosphorylation of EGFR and subsequent activation of phosphatidylinositol 3-kinase (PI3K). PI3K signaling results in an activation of Akt and TSC1/TSC2, diminishing its inhibitory effect on Rheb (Ras homolog enriched in brain), a major activator of mTOR signaling. Disruption of the TSC-complex leads to activation (disinhibition) of mTOR and may play a putative pathogenic role in lung cancer pathogenesis. Arrows represent activation; bars represent inhibitory effects.