George Gershwin. Lee Atwater. Ted Kennedy. These are just a few of the more well-known people who have succumbed to a form of brain cancer known as glioblastoma multiforme. Accounting for almost 23% of all brain cancer cases in the U.S., glioblastoma multiforme is notorious for its ability to stealthily produce the most malignant of all brain tumors known to mankind; diagnoses of this condition are extremely devastating for patients and their families because patients tend to only survive 12 to 14 months on average, even with immediate treatment. Glioblastoma is one of the most aggressive forms of astrocytoma, a cancer that originates from star-shaped cells called astrocytes. Astrocytes are found in the glial tissue, which supports the brain and enables nerve cells to function. Glioblastomas typically contain regions of dead cells, which are surrounded by a pseudopalisading array of anaplastic cells, or cells that have experienced a reversal of cell differentiation. Meanwhile, conditions such as neovascularity (abnormal blood vessel growth), and hemorrhage (blood loss) have a tendency to develop as well. Different tumors will often have varied appearances due to factors such as the amount of hemorrhage and the age of the tumor. Symptoms of glioblastoma vary depending on the location of the tumor and the regions of the brain involved. Common signs include headaches, vision loss, and decrease in motor control. Such symptoms, however, will often be manifested only in the advanced stages of glioblastoma, and even then may be attributed to other causes such as stress. Before several medical and scientific breakthroughs, glioblastoma patients were doomed to a lifespan of around two to four months; however, with various modern treatment methods, the average life expectancy of a patient diagnosed with glioblastoma has increased to around one year. Like symptoms, treatments are also based on the characteristics of the tumor—its size, and its rate of growth. In the standard treatment procedure, a patient first undergoes surgery, during which a sample of the tumor is taken for lab analysis. It is then followed by chemotherapy treatment, which is often combined with radiotherapy. Intensity modulated radiation therapy (IMRT) is an example of the latter, in which doses of radiation are administered over time through linear accelerator machines. Unfortunately, these methods generally are ultimately ineffective in treating glioblastoma, for glioblastoma tumors are often very sophisticated and may consist of several cell types. As a result, they can develop resistance to treatment methods over time. While one cell type may respond to a specific procedure, other cell types may continue multiplying, allowing the tumor to continue growing. Since the brain is very susceptible to damage, large dosages of radiation and drugs cannot be applied, greatly limiting treatment methods. Scientists have long attempted to identify the precise cause of glioblastoma, but only recently have they done so. In the December edition of Nature science journal, researchers reported the discovery of two genes, C/EPB and Stat3, which seem to work together to cause glioblastoma. The Stat3 and C/EBP genes are each responsible for regulating the growth of cancer stem cells, as well as other processes including metastasis (the spread of cancer to different organs), angiogenesis (the growth of new blood vessels that feed the tumor), and tissue invasion. When these genes are inhibited, they prevent the development of cancer, but when they are activated, they wreak tremendous damage upon the host. In studies of many human tumors throughout the body, Stat3 is one of the activated genes. While either gene expressed individually does little harm, both together allow expression of other cancer-causing genes. Researchers found that about 60 percent of patients diagnosed with glioblastoma displayed the pair of genes and faced especially bad outcomes. In a year-long study at Columbia University’s Medical Center, all of the patients with both the C/EPB and Stat3 genes died. Dr. Antonio Iavorone of Columbia University noted that these findings were “…remarkable given that it’s based on [just] the activity of two genes.’” He later added, “These are…master regulators of the most aggressive phenotype of brain tumor…We have found the real driver making the tumors.” Dr. Iavorone and other researchers hope that by identifying specific triggers of glioblastoma, they can begin exploring and experimenting with more effective treatments, namely gene therapy, in which the two activated genes causing glioblastoma would be replaced with inactivated versions. They have already met some early success. In a side study, scientists turned off the C/EPB and Stat3 genes in glioblastoma cells and then inserted these modified cancer cells into mice; amazingly, glioblastoma cancer did not grow. With such blinding advances in technology and knowledge, as well as hope, glioblastoma multiforme could very well become obsolete in future years.
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