Employing Zika Virus to Treat Advanced Brain Cancer

Scientists have discovered that the Zika virus could potentially be directed to kill brain cancer stem cells that are most resistant to treatment.
 
The Zika virus is a mosquito-borne flavivrus transmitted primarily by Aedes mosquitos, according to the World Health Organization. The virus is associated with Guillain-Barré syndrome and a cause of congenital brain abnormalities, including microcephaly.
 
In a study published in The Journal of Experimental Medicine, investigators sought to examine whether the Zika virus could kill stem cells in glioblastomas.
 
The investigators removed stem cells from patients diagnosed as having glioblastoma, and infected the tumors with 1 of 2 Zika virus strains.
 
The results of the study showed that after both strains infected the tumors, the virus killed the cancer stem cells and left other tumor cells alone.
 
“We showed that Zika virus can kill the kind of glioblastoma cells that tend to be resistant to current treatments and lead to death,” said co-senior author Michael S. Diamond, MD, PhD.
 
An estimated 12,000 individuals are diagnosed with glioblastoma annually in the United States. Standard treatment involves surgery, followed by chemotherapy and radiation; however, most tumors recur within 6 months because a small population of glioblastoma stem cells often survive treatment and continue to divide.
 
The findings of the study suggest the Zika virus combined with chemotherapy-radiation have complementary effects. Standard treatment kills most of the tumors cells, whereas the Zika virus swoops in to attack the leftover stem cells.
 
“We see Zika one day being used in combination with current therapies to eradicate the whole tumor,” said co-senior author Milan G. Chheda, MD.
 
The investigators examined whether the virus could treat cancer in living animals. Zika virus or placebo were injected into the brain tumors of 18 and 15 mice, respectively. Mice treated with Zika had significantly smaller tumors 2 weeks after injection, and survived significantly longer compared with mice given the placebo, according to the study authors.
 
Additional studies of the virus were conducted using brain tissue from patients with epilepsy, which showed the virus did not infect noncancerous brain cells.
 
The investigators also introduced 2 mutations that suppressed the virus’ ability to combat the cell’s defenses against infection. The mutant viral strain and the original parental strain in glioblastoma stem cells were tested, revealing the original strain was more potent. However, the mutant strain was also able to successful kill the cancerous cells.
 
“We’re going to introduce additional mutations to sensitize the virus even more to the innate immune response and prevent the infection from spreading,” Diamond said. “Once we add a few more changes, I think it’s going to be impossible for the virus to overcome them and cause disease.” 


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