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Cancer reversed in frogs by hacking cells’ electricity with light

Reprogramming a cell's electricity could provide an alternative to standard toxic cancer drugs and their unpleasant side effects
cancer cells
Don’t let them take charge
Eye of Science/Science Photo Library

OUR bodies are electric. It’s not just our brains and hearts – almost every cell has an electrical charge, and hacking it might be a way to treat cancer. Researchers have used light to shift the charge of cancer cells in frogs, making them healthy again.

It’s some way off being a human therapy, but this is the first use of a technique called optogenetics to target cancer, opening up the possibility of treatments that don’t use toxic drugs. “This is just the beginning,” says at Tufts University, Massachusetts. “We hope we have a new strategy for reprogramming cell activity – we’re cracking the bioelectric code.”

Nerve cells use electricity to transmit signals. They do this by letting ions flow into or out of the cell through channels in their membranes, often triggering similar changes in neighbouring cells. Other cells also communicate in this way, using their ion channels to share information about their function or movement, says Levin.

This communication seems to be important when cells divide to repair damage. But uncontrolled cell division can lead to cancer, and when a cell loses some of its negative charge, it seems to help tumours to spread. These findings have raised a tantalising prospect: could we target these electrical signals to stop cancer?

Treatments that target ion channels are already being tested – one such drug seems to have kept a man’s brain tumour . However, the drug had toxic side effects, so he stopped taking it.

Instead of using drugs to target ion channels, Levin’s team is using optogenetics. This technique involves injecting a gene into cells that makes a light-sensitive protein. Shining a laser on these newly sensitive cells can then alter their behaviour in different ways, depending on the protein used.

“We hope we have a new strategy for cancer – we’re cracking the bioelectric code”

To see if optogenetics can change the flow of ions into a cell to revert it to a non-dividing state, Levin’s team have turned to frog embryos, which are particularly easy to work with. They inserted a gene that predisposes animals to cancer, adding a gene for a light-activated ion channel at the same time.

A week later, the tadpoles had hatched and developed tumours. While not exactly the same as human cancers, these tumours had many of the same properties, growing, spreading and forming their own blood supply in a similar way.

When the team pointed a laser at the tadpoles, around a third of the tumours stopped developing. This is an impressive result for a cancer treatment, says at the University of York, UK, although he says it is hard to know how large the effect would be in humans.

In the tadpoles, cells that had been cancerous looked healthy again, and were absorbed back into other body tissues. “They’ve reprogrammed the cancer cells, by altering the electrical status of the cell,” says  at Loyola University Chicago. “They are not cancer cells anymore.”

If the approach works in humans, breast and skin cancers might be targeted first, as they are easy to shine a laser on. Levin hopes his approach will eventually offer an alternative to standard cancer drugs. We might find that drug-free treatments have fewer side effects, he says.

Gentile agrees. Cancer drugs that kill dividing cells don’t work perfectly, and the side effects can be worse than the disease itself in some cases, he says. “Levin has shown that you don’t need to kill the cells – you can take them back to a normal state.”

Eyes on the prize

Optogenetics is the hottest tool in experimental neuroscience, but can it treat human diseases?

The technique inserts genes for light-activated proteins into cells, so lasers can change their behaviour. It could have a range of uses (see main story), but a prime candidate is to restore sight to people who have lost the light-sensitive cells in their eyes.

This has already been done in blind mice, and now researchers are turning to humans. Ed Boyden, who originally helped develop optogenetics, and his colleagues at are one of several groups working on disorders like age-related macular degeneration.

Meanwhile, Paris-based company plans to test a treatment for a condition called retinitis pigmentosa in humans next year. hopes to start testing its version of the treatment in a group of people in Texas as early as next month.

This article appeared in print under the headline “Bioelectric cancer hack”

Topics: Biology / Cancer