Antioxidant Adaptive Response of Malignant Glioma Related to Resistance to Antitumor Treatment

Glioblastomas are the most frequent and most malignant nervous system tumors [Stewart & Kleihues, 2003]. Despite technological advances in surgical treatment and new regimens of radiotherapy combined with chemotherapy, the median survival of patients with these tumors is approximately 1 year, and only 3% of patients survive more than 3 years [Stupp et al., 2005]. Glioblastomas have been traditionally defined as two clinically and cytogenetically distinct diseases: the primary or de novo glioblastomas and the secondary glioblastomas. The latter commonly appear in younger people (median age at onset ~45 years) as low-grade gliomas and possess aberrations in genes encoding platelet-derived growth factor receptor (PDGFR) and TP53 [Stewart & Kleihues, 2003]. Primary glioblastomas occur more frequently (>80% of cases) and develop rapidly in older people (median age at onset ~60 years); survival of patients with such tumors is short, less than 3 months [Stewart & Kleihues, 2003]. The genetic profile of primary glioblastomas includes amplification and overexpression of the gene encoding epidermal growth factor receptor (EGFR), mutations of the phosphatase and tensin homolog (PTEN) gene, p16INK4A deletions, and loss of chromosome 10 [Stewart & Kleihues, 2003]. Several inhibitors that target EGFR or its downstream signaling cascade including Akt and mTOR have been evaluated for potential application in glioblastoma treatment [Krakstad & Chekenya, 2010]. Recent clinical trials of EGFR inhibitors, however, showed no therapeutic benefit [Prados et al., 2006; Rich et al., 2004].