Cancer drugs may fight smallpox

2019-03-02 09:07:03

By Debora MacKenzie Cancer drugs have unexpectedly led to an entirely new way to beat viral infections – and particularly smallpox – a new study suggests. Viruses are hard to stop and, with few exceptions, drugs aimed at killing viral infections have not worked nearly as well as the antibiotics that kill bacteria. Now, US scientists have found that an experimental drug aimed at stopping the uncontrolled growth of cancer cells actually prevents the smallpox virus from replicating inside human cells, and can save mice from dying of a closely related virus, Vaccinia. Viruses succeed by invading a cell and hijacking the “machinery” used by actively dividing cells to replicate their own DNA. But most cells frequently exposed to viruses – such as skin cells or those lining the lungs – are not actively dividing and so have their replication machinery turned off. Viruses such as smallpox have learned to turn it back on by making their own copies of the hormones and growth factors that normally induce cells to divide. Since the overexpression of the receptors for these growth factors in cancer cells is one of the reasons cancers grow uncontrollably, cancer research has focused on finding molecules that block the receptors. Ellis Reinherz and colleagues at the Dana Farber Cancer Institute in Boston, US, had already discovered that smallpox and its relatives produce molecules similar to the growth factors naturally produced by the body to signal these very same receptors, called erb-B1. They use these factors to turn their host cell’s replicating machinery on. “We reasoned that if the viral factor’s stimulatory activity was blocked, then viral growth might be curtailed,” say the researchers. They used an experimental cancer drug to block the erb-B1 receptor, and found that this did indeed stop the smallpox virus from propagating in human cells in culture. The team then gave the drug to mice and infected them with Vaccinia. The drug saved all the treated mice from dying at doses of virus that killed all of the untreated mice. It worked even better when combined with an antibody highly specific for Vaccinia. And the combined approach was better than the added effects of each separately, possibly because they strongly stimulated the mouse’s own immune response. One drawback, Reinherz notes, is that the mouse treatment only worked if the drug was given before the virus. Although treating the mouse after the viral infection began did reduce the severity of infection the mice still died. The authors suspect that in a slower-developing disease, as pox infections are in humans, the combined treatment might have a better chance of beating the virus. The real advantage, though, is that this approach does not target the virus itself – it targets the machinery, or signalling pathway, of the host cell, which the virus hijacks. Like bacteria and antibiotics, viruses evolve resistance to antiviral drugs that are aimed at the virus’s own components. “The advantage of targeting signalling pathways is that cells are far less likely to mutate than the viruses themselves, making it improbable that drugs will lose their potency,” says Reinherz. Journal reference: Journal of Clinical Investigation (DOI: