Anahita Kodali 23′
Figure 1: Glioblastomas are incredibly aggressive and have some of the highest mortality rates of all forms of cancer – the median survival rate for patients with glioblastomas who undergo all treatment possible is 15-16 months [6]. (Image Source: Wikimedia Commons)
Glioblastomas are notoriously difficult to treat. Once discovered, surgical removal of the entire tumor mass is nearly impossible because glioblastomas generally do not have easily identifiable clean margins (surrounding tissue that is free of cancer cells). Along with surgery, many cancers are treated using drugs. However, for glioblastomas specifically, drugs are not always feasible in fighting glioblastomas because most drugs cannot pass the blood-brain barrier (BBB), as the BBB has a lining of endothelial cells that prevent materials in the blood from getting into the brain [2]. Glioblastomas are also often directly adjacent to parts of the brain critical to cognitive function, so doctors need to be extremely careful to not damage healthy tissue [3]. Despite these difficulties with treatment, brain cancers are not infallible. Most, including glioblastomas, cannot launch immune attacks against invading viruses, meaning that viruses have the potential to be powerful tools in eliminating tumors [4].
The Yale team created a chimeric virus using a glycoprotein with a mucin-line domain from wild-type Ebola. Chimeric viruses, amalgamations of genes from several different viruses, allow researchers to administer viruses to patients without fear of deadly infection (if they used the wild-type virus with no alterations, there would be a significant chance that patients, already weakened because of cancer, would actually contract the disease). In this case, the researchers chose the mucin-line domain from Ebola because it both helps the virus avoid immune response from its host and also contributes to its lethality. Once the chimera was created, it was injected into mice with glioblastomas. The researchers found that it was able to target and kill the tumors [5].
Professor van de Pol hypothesized that the benefit of the chimera was its ability to selectively target cancer cells because cancer cells did not have an immune response to the pathogen while the body’s natural cells were able to fight the virus off. In addition, mucin-line domain makes virus replication much slower than wild-type viruses, lowering the risk for patients. Beyond glioblastomas, the study has several implications for the future of glioblastoma treatment; by using chimeras with other treatment, like surgery or drugs, doctors and researchers will be able to more effectively kill tumors while preventing reoccurrence of these cancerous cells [4].
References:
[1] Ebola virus disease. (2020, February 10). World Health Organization. Retrieved from https://www.who.int/news-room/fact-sheets/detail/ebola-virus-disease
[2] Pardirdge, W. M. (2012). Drug transport across the blood–brain barrier. Journal of Cerebral Blood Flow & Metabolism, 32(11), 1959–1972. doi: 10.1038/jcbfm.2012.126
[3] Glioblastoma: why these brain cancers are so difficult to treat. (2016, June 29). News.Cancer Research. Retrieved from https://news.cancerresearch/glioblastoma-why-these-brain-cancers-are-so-difficult-to-treat/
[4] Yale University. (2020, February 12). Scientists find ally in fight against brain tumors: Ebola. ScienceDaily. Retrieved from www.sciencedaily.com/releases/2020/02/200212150149.htm
[5] Xue Zhang, Tingting Zhang, John N. Davis, Andrea Marzi, Anthony M. Marchese, Michael D. Robek, Anthony N. van den Pol. Mucin-like domain of Ebola virus glycoprotein enhances selective oncolytic actions against brain tumors. Journal of Virology, 2020; DOI: 10.1128/JVI.01967-19
[6] What Is Gliobastoma? (n.d.). healthline. Retrieved from https://www.healthline.com/health/brain-tumor/glioblastoma#survival-rates-and-life-expectancy