Researchers are beginning to understand why certain brain tumors are so hard to stop.
Three studies published Wednesday in the journal Nature found that these deadly tumors integrate into the brain's electrical network and then kidnap signals from healthy nerve cells that stimulate their own growth.
"They are like vampires," who feed on brain activity. Frank Winkler, neurologist at the University of Heidelberg and author of one of the studies.
But research also offers hope. The results suggest that some brain tumors may be slowed down with drugs that inhibit the activity of certain brain cells or disrupt the connections between tumor cells and healthy cells.
Two of the three studies, including Winkler's, looked at high-grade glioma studies, which include glioblastoma, the cancer that killed Senator John McCain in 201
"High-grade gliomas are indeed a stubborn disease, and we have made little clinical progress in effectively treating these terrible brain tumors." Michelle Monje, Professor of Neurology and Neuroscience at Stanford University and author of a second study.
In 2015, Monje was part of a team that found that high-grade gliomas grew faster when the brain cells around them became more active.
Monje's team suspected this because active neurons produce a substance that acts like fuel for gliomas. The team used human glioma tumors in the brains of mice that had been genetically modified so they could not produce this substance.
"There was not just a slowdown in tumor growth – there was complete stagnation," Monje says. The study was published in 2017.
However, Monje was pretty sure that high-grade gliomas in some way make healthy brain cells more active and produce more fuel. And she believed the cancer cells could do this by connecting to healthy neurons and abducting the electrical signals they produce
. The new studies seem to confirm this and even show how.
Monje's team found that these are some cancerous cells forming synapses – the connections between neurons – that could be seen with an electron microscope. They also found evidence of a more primitive direct link between cancer cells and healthy brain cells.
Tumor cells "integrate into neuronal circuits in the brain," says Monje, using these compounds to influence the behavior of neurons. "The cancer cells themselves promote neuronal activity, which then drives the growth of the cancer."
Winkler and his team found virtually the same thing with another set of glioma cells. "There is an enormous amount of networks," he says.
A third study, conducted by researchers in Switzerland, found that breast cancer cells can also connect to neurons when they move to the brain.
Research is likely to have a seismic impact on brain cancer research, says Andres Barria, a neuroscientist at the University of Washington, who is studying synapses and writing an editorial accompanying the three studies.
"My reaction was, wow," he says. "Showing that [a tumor cell] is actually making real connections, as normal neurons do, is very amazing."
And this discovery could lead to new and better therapies for high-grade gliomas, which today usually kill a patient within two years.
"We hope that by reducing the electrical signals that tumors receive from the normal brain, we can complement existing therapies and extend survival and improve quality of life," says Monje.
Her team showed that an anti-epileptic drug called perampanel reduced the glioma-type growth rate in mice by 50%.
But Barria advises caution when it comes to drugs that affect the connections between brain cells.
"Synapses are everywhere in the brain," he says. "Just targeting the synapses between cancer cells and neurons becomes difficult."