ABSTRACT
The National Cancer Institute projects that there will be 23,770 new cases of nervous system cancers, including brain cancers, in the United States in 2016 and 16,050 deaths due to the disease [1]. This disease has an extensive economic toll, estimated at $4.9 billion in treatment costs alone in 2014, and yet has one of the worst cancer-specific survival rates [1,2]. Glioblastoma multiforme (GBM) is the most common primary brain tumor and also the most aggressive, with a five-year mean survival rate of only 3–5% [3,4]. Without treatment, the average survival time for GBM patients is typically three months and with treatment, the median survival is 14.6 months [5,6]. Gliomas arise due to an accumulation of genetic and chromosomal alterations in non-neuronal glial cells, which provide a variety of support functions for the neurons in the central nervous system. Gliomas are generally classified in two ways, by their cell type and tumor grade. Cell types can consist of either ependymoma, astrocytoma, oligodendroglioma, or a combination of these. A grading system is then used to further classify the tumor based on pathologic evaluation. The World Health Organization classification system is the most common, and consists of grades I through IV. Low grade gliomas (LGG) – grade I and grade II – are less aggressive and can often be treated with surgical resection alone or in combination with radio- and chemotherapy [7]. High grade gliomas (HGG) – grade III and grade IV – are considered very aggressive and are histologically highly heterogeneous, containing both stromal and neoplastic tissues [8]. Grade IV tumors, including GBM, are mitotically active, necrosis-prone neoplasms and are usually associated with swift disease progression and a fatal outcome.
