Nonphagocytic NADPH oxidase NOX1-, NADPH oxidase NOX4-, and NADPH oxidase NOX5-derived ROS play a prominent role in the initiation and progression of cancer through the regulation of cellular signal transduction pathways (114, 159, 328, 342) and through modulation of the growth modulation signaling that supports the autonomous growth of cells, angiogenesis, invasion, and metastasis (240, 260, 352). This evidence concerns the gene NOX4 and cancer.