(A) Hydrogen peroxide (H2O2) is required for activation of a number of cellular pathways involved in cellular proliferation. (B) Cancer cells generate higher levels of ROS that are essential for tumorigenesis. Genetic alterations leading to activation of oncogenes (PI3K, MAPK, HIFs, NF-κB) and loss of tumor suppressors (p53) coordinate an elevated redox state. ROS is also generated from increased oxidative metabolism and hypoxia in rapidly expanding tumors. Cancer cells also express elevated levels of cellular antioxidants (SODs, GSH, GPx, PRx) in part through NRF-2 to protect against oxidative stress-induced cell death.