Evolving evidence implicates cytomegalovirus as a promoter of malignant glioma pathogenesis

Malignant gliomas are the most common cerebral tumors, account for about 4% of cancer deaths, and grade IV gliomas, glioblastoma multiforme (GBM), are the most aggressive [1]. Despite recent advances in radiotherapy and chemotherapy, the prognosis for GBM patients is a median survival after diagnosis of about 14 months [1]. No significant gains in the understanding of the etiology of GBM has occurred in the last several decades, and except for very rare genetic cancer syndromes and exposure to ionizing radiation, there is no known cause for gliomas [2].Despite the lack of a known etiological agent for GBM, recent findings have led to important insights into molecular pathways involved in gliomagenesis. These findings suggest that GBM cells may arise from two pathways. One potential pathway would involve post-mitotic astrocytic cells that have de-differentiated into immature tumor cells. Alternatively, the tumor arises by the immortalization and transformation of resident neuo-glial precursor stem cells (NPCs) in the adult brain [3,4].One of the most important recent observations regarding the biology of GBM is that these tumors, like other hematological and solid tumors, are comprised of a subpopulation of tumor initiating cells with stem-like characteristics, often termed "cancer stem cells" or glioma stem cells (GSC) [5,6]. These cells often express the CD133 surface glycoprotein, and are therefore defined as CD133+ cells [5,7]. GSCs likely represent the most important targets of the GBM cells in terms of therapy, since these cells are more resistant to radiation and chemotherapy, and also may be immunosuppressive [7-9]. These cells also appear to play a critical role in re-initiating tumor growth after standard therapies, and thus may play a central role in tumor recurrence. Indeed, in vitro, these cells can act as tumor-founding cells down to the single cell level, and the tumors they produce in animal models closely resemble the main histological properties of