The combination of oxidative insult generated during infection, decreased O2 delivery to cells and tissues and contributed to increase hypoxic microenvironments. Moreover, the extent of ROS-induced oxidative damage can be exacerbated by decreased efficiency of antioxidant and cytoprotetive defense mechanisms. Malignant glioma, including anaplastic astrocytoma and glioblastoma multiforme, account for more than 50% of all primary brain tumors, with GBM being the most common malignant brain tumor in adults. GBM is highly invasive and angiogenic, resulting in mortality rates higher than those for any other brain tumor, with a median survival of 12 to 15 months. Other than the introduction of the chemotherapeutic drug Temozolomide the treatment protocol has generally not changed over the past decades. Because it is well tolerated and has been shown to prolong patient survival, TMZ is WZ8040 currently the standard chemotherapy drug adopted for the treatment of high grade glioma of astroglial origin. TMZ is a lipophilic prodrug that is converted to the active metabolite methyltriazenolimidazole-carboxamide at physiological pH, resulting in the formation of methyl adducts at the O6 position of guanine in the DNA. This methylation leads to mismatch pairing with thymine during DNA replication and to subsequent DNA strand breaks which eventually cause apoptosis. In GBM samples, TMZ resistance has been linked to the cellular expression of O6 – methylguanine DNA methyltransferase. MGMT actively repairs the DNA damage induced by TMZ treatment by removing the O6 -methyl adducts. In fact, the greatest survival benefit provided by TMZ treatment was reported for tumors containing a methylated MGMT gene, which has a reduced expression and activity of this repair protein. Despite the benefits of TMZ treatment, a cure for GBM remains elusive; and almost all patients suffer recurrence, underlining the importance of augmenting the efficacy of existing treatments as well as developing new therapeutics. Most chemotherapeutic agents cause damage to normal cells and tissues, particularly to those with high proliferative indices such as the bone marrow, lung and gut, resulting in severe short- and long-term side effects which make toxicity the doselimiting factor for most chemotherapeutic-treatments. We have previously demonstrated that fasting or short-term starvation can selectively protect normal cells, mice and potentially patients from chemo-toxicity without reducing the therapeutic effect on cancer cells, a phenomenon we termed Differential Stress Resistance. The starvation-induced DSR may be attributed to the redistribution of finite energy and resources from reproduction/growth to cellular protection/maintenance in normal, but not cancer cells. The coordinated physiological responses to nutrient scarcity are in part mediated by reduced insulin-like growth factor 1 signaling and the subsequent activation of cellular protection mechanisms. In contrast, tumor cells harbor oncogenic mutation in growth signaling genes, including IGF1R, PI3K, PTEN and Ras, which render them self-sufficient in proliferation signaling and unresponsive to starvation conditions. Glucose is the main energy source for cells, particularly for highly proliferative ones such as malignant cells. Many cancer cells, including glioma cells, display elevated glucose uptake and glycolysis even in the presence of oxygen, a phenomenon known as the Warburg effect. In fact, elevated blood glucose is associated with an increased cancer rate and is thought to be a major risk factor for a variety of malignancies.