EGFR and glioma: Interestingly, several evidences suggest that ROS production is constitutively elevated in GBM, without the requirement of any triggering signal like nutrient starvation: first, EGFR is a frequent mutation in glioma and its constitutive activation leads to ROS production [27] and ROS can also directly phosphorylate signaling proteins and increase flux through PI3K/AKT and MAPK/ERK to potentiate oncogenic signaling [28]; second, increased ROS levels in GICs contribute to the oxidative base damage and single-strand DNA breaks found in GICs [8].