Molecular Pathogenesis

Patterns of molecular genetic abnormalities have been associated with specific types of HGGs [3] (Fig. 10.1). The high frequency of genetic alterations that inactivate p53 and augment EGFR (epidermal growth factor receptor) activity and its downstream pathways, and their presence in the most common forms of HGG, have led to innovative therapeutic strategies that target these molecules and in some cases directly involve the neurosurgeon. These molecular genetic changes are presumed to underlie gliomagenesis and/or progression to HGG and have been most rigorously studied in glioblas-toma. Secondary GBMs arise predominantly in younger patients from pre-existing lower grade tumors, while primary GBMs more commonly occur in older patients and are presumed to arise de novo from a target cell of origin. The former are more likely to have mutations that inactivate p53 function, while the latter typically have overactivation of EGFR-mediated pathways through various mechanisms such as gene amplification or mutation. In GBM, this latter abnormality is often due to the expression of a truncated, and constitutively activated, EGFR called "EGFRvIII", which is being investigated as a target for immunotherapy. In contrast, the molecular genetic changes that lead to the

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Cure Your Yeast Infection For Good

Cure Your Yeast Infection For Good

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