Hypothetical model of the effect of NOX inhibition on downstream cell signaling. Empirical evidence strongly suggests that NOX-associated ROS promote the activation of JAK/STAT and Akt signaling pathways, and that NOX inhibition with DPI or its analog DTI enhances the activity of intracellular PTP, thus dephosphorylating key signaling kinases. DPI, diphenylene iodonium; DTI, di-2-thienyliodonium; PTP, protein tyrosine phosphatases; ROS, reactive oxygen species. Adapted from Figure 8 in Doroshow et al. (58).