Hope for Glioblastoma: Resection and New Treatments: Page 2 of 2

Hope for Glioblastoma: Resection and New Treatments: Page 2 of 2


Some of the underlying genetic abnormalities associated with GBM include overexpression of the epidermal growth factor receptor (EGFR) gene and its most common deletion mutant variant III (EGFRvIII).8 Tyrosine kinase inhibitors have been used to block the ligand-activated tyrosine kinase activity of EGFR. Some tumors have been found to respond to this genetic attack, according to Friedman.

EGFR kinase inhibitors alone or in combination with other agents such as rapamycin are expected to be beneficial in selected patients, explained Friedman. Only 10% to 20% of patients with GBM reportedly responded to EGFR kinase inhibitors, though.9 Loss of expression of tumor suppressor gene PTEN and its protein phenotype is thought to produce cellular resistance to EGFR kinase inhibitor therapy in GBM.

Reduced sensitivity to EGFR kinase inhibitors in patients with GBM, therefore, has been linked to tumor coexpression of EGFRvIII and PTEN.9 The identification of this genetic and phenotypic relationship is an important step in the development of a tumor-specific treatment for GBM, according to Friedman.

"Whether these GBM tumors are EGRFvIII-positive or PTEN wild type—the latter of which augurs a particularly good response to erlotinib [Tarceva]—or whether the tumor response is linked to other molecular profiles, we will begin to unravel the molecular subsets that will predict a better outcome," Friedman said. He added that "once patients with GBM are treated with multi-modality overlapping therapies, we will begin to see a desperately needed increase in the cure and survival rates."



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