Molecular pathogenesis of malignant glial tumors

Malignant glial tumors are the most aggressive and difficult to treat neoplasms arising in the brain. More than 22,000 people in the United States are diagnosed with a malignant glioma annually, and most will die within the first two years from diagnosis. Traditionally, gliomas have been categorized based solely on tumor histological features. However, expression studies have found that molecular signatures can be used to categorize these tumors into subclasses that more effectively predict patient outcome. The heterogeneity between tumors as well as within individual tumors makes understanding the molecular aspects of tumorigenesis extremely important. Several genetically engineered mouse models (GEMMs) of glioma have been developed that recapitulate the molecular alterations observed in the human disease. GEMMs of glioma have allowed researchers to more closely study the role of cancer stem cells (CSC) in gliomagenesis as well as the relevance of signaling within the CSC microenvironment. Knowledge of the underlying molecular signatures of malignant glial tumors coupled with the existence of a variety of human disease-relevant GEMMs of this tumor type provide researchers and clinicians with valuable resources for the discovery of new drug targets.