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Not long ago, Zika virus was dominating headlines. A new infection was hardly ever heard about before then, yet is now affecting hundreds of thousands of people in Latin America, causing disfiguration and microcephalia in new-born babies. Microcephalia is caused by severe delayed and abnormal development of the brain, resulting in the range of intellectual disability, dwarfism, poor motor functions and speech. With no cure or even preventive vaccination available, many women in the most affected regions were reportedly considering postponing any planned pregnancies.
The virus was actually discovered back in 1947 in Zika forest in Uganda (and this is where its name comes from). The pathogen is related to better known viruses causing dengue and yellow fever. The disease is spread predominantly by one type of mosquito and was a rare occurrence until the epidemics of 2015–2016, when in Brazil alone well over 100,000 cases were reported. The disease caused particular concern as it coincided with the run-up to the 2016 Olympic games in Rio de Janeiro.
Apart from mosquitoes, the virus can be spread through sexual contact and from mother to child during pregnancy or at delivery. The latter way of transmission is a particular concern: while adults suffer only very mild symptoms (fever and rush), children infected during pregnancy suffer major brain damage. The reason for this is that viral infection delays brain development.
Further research identified a more specific reason: Zika virus specifically targets neural progenitor cells, the cells responsible for production of other neurons. This is what makes the virus very dangerous for the developing fetus. Neuron progenitor cells are abundant in the developing fetal brain. However, only a few are left in the brain of adults. In adults with completely formed brain, Zika virus infection causes only mild symptoms, if any (Zika fever). But the specificity with which the virus targets neural progenitor cells gave researchers an idea that might revolutionize the treatment of one of the deadliest types of brain cancer—glioblastoma.
Glioblastoma is one of the most difficult types of cancer to treat, with patients rarely surviving even one year after diagnosis. Unfortunately, this is also one of the most common types of brain cancer. Approximately 12,000 people are diagnosed with glioblastoma in the US alone. The quick return of the disease even after aggressive surgery is caused by the survival of a few glioblastoma stem cells. Many types of cancer like glioblastoma grow due to the existence of cancer stem cells that give rise to other tumor cells. The glioblastoma stem cells remain almost unaffected by all radio- and chemotherapy regiments currently used to treat this malignancy, even though these therapeutic approaches do kill other cells in the tumor. They also successfully avoid detection and elimination by the immune system, allowing the regrowth of cancer in a short period of time after surgery, replenishing the cancer cells eliminated by therapy.
Researchers noted that glioblastoma stem cells are, in many ways, very similar to normal neural progenitor cells. Therefore, infecting a person with glioblastoma with Zika virus might help in treating the disease by eliminating the stem cells. This was a core idea that researchers initially tested on cancer cells from tumors obtained from surgeries. It turned out that the virus does indeed kill cancer stem cells, leaving other cancer cells almost unaffected.
To further make sure that the virus doesn’t affect the normal cells of the brain, scientists have performed experiments on brain tissues from patients with epilepsy. The tests did not detect any damage to these cells due to viral infection.
The findings suggest that combining traditional chemotherapy with treatment with Zika virus may help to eliminate stem and non-stem cancer cells. Such an outcome will most certainly be beneficial for the patients.
To test the idea further, scientists injected Zika virus directly into the brain of mice with brain tumors. In all animals infected with the disease, tumor growth slowed down significantly and the animals survived longer.
The researchers suggest that Zika virus can be injected into the brain of a glioblastoma patient at the time of surgery. The subsequent chemotherapy will remove any remaining cancer cells that survived surgery, and Zika virus will kill the residual glioblastoma stem cells. The published findings also suggest that the virus can be further engineered to be more easily eliminated from normal healthy brain cells using the patient’s immune system. Less harmful strains of the virus have already been developed to this end and have demonstrated some success in animal experiments.
It remains to be seen if a successful therapeutic approach to treat deadly glioblastoma can be developed using Zika virus. The path to future use of Zika-based treatment in hospitals will likely be long. The original results, however, are very encouraging. This new approach is another fascinating example of a growing number of new innovative tools that are currently being developed to treat a variety of cancers.
Bleeker, Fonnet E, Molenaar, Remco J; Leenstra, Sieger (2012) Recent advances in the molecular understanding of glioblastoma. Journal of Neuro-Oncology. 108 (1): 11–27. PMC3337398.
Lathia J, Mack SC, Mulkearns-Hubert EE, Valentim CLL, Rich JN (2015). Cancer stem cells in glioblastoma. Genes & Development, 29(12), 1203–1217. doi:10.1101/gad.261982.115.
Rasmussen, Sonja A, Jamieson, Denise J, Honein, Margaret A, Petersen, Lyle R (2016) Zika Virus and Birth Defects — Reviewing the Evidence for Causality. New England Journal of Medicine. 374 (20): 1981–7. doi:10.1056/NEJMsr1604338.
Zhu Z, Gorman MJ, McKenzie LD, Chai JN, Hubert CG, Prager BC, Fernandez E, Richner JM, Zhang R, Shan C, Wang X, Shi P, Diamond MS, Rich JN, Chheda MG. Zika virus has oncolytic activity against glioblastoma stem cells. The Journal of Experimental Medicine, Sept. 5, 2017 doi:10.1084/jem.20171093.
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