The virus may yield a potent weapon against a deadlier disease.
Of the afflictions routinely visiting the tropics, Zika virus is surely one of the most alarming. A contagion known mostly for fever and chills took on a deadly new face in Brazil in 2015, when it was linked to severe brain deformities in newborns, including a spike in infant microcephaly, or babies with undersized craniums. And all of this was unfolding amid Brazil’s gathering fiscal chaos, which undercut funding for science even as public health authorities were scrambling to contain other mosquito-borne illnesses such as dengue fever, chikungunya and a resurgent centuries-old menace, yellow fever.
So who would have thought that such a scourge could be turned into a treatment? Yet Zika’s destructive powers were precisely what caught the attention of geneticists and biological researchers at the University of Sao Paulo, known as USP.
While their peers were scouring for strategies to fight or prevent Zika, from developing a vaccine to using robots to release sterile bugs into the wild to sabotage mosquito populations, the Brazilian team concentrated on repurposing the virus’s deadly properties to fight an even deadlier threat, brain cancer.
The scientists took their cues from the epidemic itself. Knowing how Zika attacked the developing brain, they wondered if the virus could have the same impact on brain tumors. “There’s a major effort to study viruses for their potential in treating illness,” Oswaldo K. Okamoto, a biologist and cancer researcher at USP’s department of genetics and evolutionary biology, told me. “At first we assumed that other institutions were already on this.”
As it happened, Zika was still a research frontier. So to test their hunch Okamoto and his colleagues devised a laboratory experiment to introduce the virus to cancerous cells of the central nervous system.
To their surprise, the lab tests showed that Zika mostly skipped normal tissue and went straight at the cancer cells, first in test tubes and later in mice carrying human tumor cells.
While virus-free mice died of cancer within a few weeks, animals infected with Zika lived longer, developed smaller tumors, suffered fewer cases of metastasis, and in some cases went into full remission. “At each phase of the study we had new surprises,” said Okamoto. “Just a small dose of the virus inoculated into the mice proved to be enough to eliminate tumors and stop the disease from spreading.”
The researchers also studied Zika’s effect on other tumors, such as prostate, breast and colorectal cancers, but found repeatedly that the virus had a predilection for cancer of the brain.
What’s especially encouraging is that Zika’s preferred targets include some of the most harrowing tumors of the central nervous system in children: medulloblastoma and the rarer but deadly ATRT. Young children diagnosed with such cancers respond poorly to conventional therapies such as chemotherapy, radiation and surgery, and survivors often are left with neurological damage, Okamoto told me.
The Brazilians were not the only ones chasing Zika’s secrets.
Simultaneously, a team at Washington University School of Medicine in St. Louis came up with similar findings after injecting the virus into mice carrying glioblastoma, another aggressive brain tumor that resists conventional treatment and can kill in just 12 to 14 months. There, too, the results were promising.
Treating disease with disease has a long track record. Many vaccines are developed from trace elements of pathogens that trigger the body’s immune response. And consider the recent study that suggested how failing to expose infants to germs can leave them susceptible to leukemia.
The study of viruses has raised the quest for hair-of-the-dog therapy to a new level. Known for their resilience and stealth, viruses are capable of stealing unscathed inside cells to unleash destruction. Today scientists are looking to harness that same surreptitiousness to deliver potentially cancer-beating drugs and chemicals, or trigger the body’s own immune response.
Medical experts call these oncolytic viruses, or viruses that combat cancer naturally or through retooling in the laboratory. Scores of experiments and trials with viruses like polio, measles and herpes are already in train, although to date only one has been approved by the the U.S. Food and Drug Administration. Research into the evolving Zika epidemic could push oncolytics even further.
“Research tells us that cancer stem cells are especially resistant. They can repopulate a tumor even after aggressive treatment. So the dream has been to find, target and kill these cells,” neuro-oncology specialist Milan Chheda, who is part of a team studying Zika at the Washington University School of Medicine, said in an interview. “Zika naturally hones in on cancer stem cells. We’re leveraging natural properties of the virus.”
It’s still early days in Zika oncolytics. Before scientists can offer treatment, they must test the impact the tumor-killing virus has on healthy tissue, a challenge that demands perhaps years more of rigorous laboratory experiments followed by human trials.
The good news is that international research institutions and the pharmaceutical industry are closely following the lab work, while a new interdisciplinary culture of medical research has helped kick-start the field. “It’s a much different world than 20 years ago,” said Chheda. “Zika is an old disease and we have yet to make much of a dent in it. To make major advances we know we need to tap a variety of experts from multiple laboratories.”
Brazilian bureaucrats should take note. Even as the University of Sao Paulo research team was ramping up the study that would land on the cover of the premier medical journal Cancer Research, government bean-cutters were laying siege to scientific inquiry. It’s tough to fight deadly threats when the doctor isn’t in.