FIG. 3.

Redox mechanisms for drug resistance. IR and/or intrinsic ROS generate an oxidative tumor microenvironment, which can modify the anticancer drug, rendering it less effective (e.g., erlotinib and its oxidized forms shown in the bottom) and the protein target itself (e.g., EGFR). IR and/or intrinsic ROS also affect tumor signaling, cell metabolism, and epigenetics in a cyclic way resulting in changes in the cellular phenotype, which, in turn, would impact tumor progression and response to therapies. EMT, epithelial-mesenchymal transition; IR, ionizing radiation; MET, mesenchymal-epithelial transition. To see this illustration in color, the reader is referred to the online version of this article at www.liebertpub.com/ars.