An Israeli company is conducting human tests for a device that uses weak electric fields to kill cancer cells but has no effect on normal cells. The device is in late-stage clinical trials in the United States and Europe for glioblastoma, a deadly brain cancer. It is also being tested in Europe for its effectiveness against breast cancer. In the lab and in animal testing, treatment with electric fields has killed cancer cells of every type tested.
The electric-field therapy was developed by Yoram Palti, a physiologist at the Technion-Israel Institute of Technology, in Haifa, who founded the company NovoCure to commercialize the treatment. Palti’s electric fields cause dividing cancer cells to explode while having no significant impact on normal tissues. The range of electric fields generated by the device harms only dividing cells. And since normal cells divide at a much slower rate than cancer cells, the electric fields target cancer cells. “An Achilles’ heel of cancer cells is that they have to divide,” says Herbert Engelhard, chief of neuro-oncology in the department of neurosurgery at the University of Illinois, Chicago.
Even after chemotherapy, radiation therapy, and surgery, about 85 to 90 percent of glioblastoma patients’ cancer still progresses, and their survival rates are low, says Engelhard. He has about 10 glioblastoma patients enrolled in the trial, which is testing the unusual treatment in patients for whom all other approaches have failed. Engelhard says that the results are encouraging but that it’s too early to comment on the treatment’s efficacy.
The electric fields’ different effects on normal and dividing cells mostly have to do with geometry. A dividing cell has what Palti calls “an hourglass shape rather than a round shape.” The electric field generated by the NovoCure device passes around and through round cells in a uniform fashion. But the narrow neck that pinches in at the center of a dividing cell acts like a lens, concentrating the electric field at this point. This non-uniform electric field wreaks havoc on dividing cells. The electric field tears apart important biological molecules, such as DNA and the structural proteins that pull the chromosomes into place during cell division. Dividing cells simply “disintegrate,” says Palti.
Palti, who for years has been studying the effect of electric fields on cancer and normal cells, says that he has verified this mechanism in computer models and experiments in the lab. “The physics are solid,” says David Cohen, associate professor of radiology at Harvard Medical School.
Patients in the glioblastoma clinical trial wear the device almost constantly, carrying necessary components in a briefcase. A wire emerging from the briefcase connects to adhesive electrodes covering the skull. Alternating electric fields pass through the scalp, into the skull, and on to the brain. The Food and Drug Administration approved the device for late-stage clinical trials for glioblastoma following promising results from a pilot study in 10 patients, one of whom had a complete recovery.
One exciting result from his studies, says Palti, is that there is “excellent synergy between electric-field treatment and chemotherapy.” In an unpublished lab study of several types of cancer, he says, adding electric-field treatment makes several chemotherapeutics more effective at lower doses. NovoCure is now conducting a pilot trial in Europe in which patients begin electric-field treatment in conjunction with chemotherapy when they are first diagnosed with glioblastoma. The results are preliminary, but, Palti says, “I strongly believe that the combination treatment will … enable one to reduce the chemo doses to levels where their side effects will be significantly reduced.”
Palti says that after more than 200 cumulative months of electric-field treatment in several patients, there have been no side effects beyond irritation of the scalp. “So far, toxicity seems to be low,” says Engelhard. This stands in stark contrast to chemotherapy and radiation, which cause many side effects, including nausea, hair loss, and fatigue.
One worry is that the electric-field treatment could affect healthy cells that are dividing. The electric fields emerging from the electrodes can’t be focused, says Cohen, and although they are primarily concentrated in the brain in the glioblastoma trial, they may also reach other parts of the body where cells are dividing. Cells in the bone marrow, for example, multiply at a great rate to create red blood cells and immune cells. But Palti says that the electric fields have no effect on blood-cell counts. The bone and muscle surrounding the marrow appear to protect the cells..
It’s unclear how long patients will need to wear the device. “We’re hesitant to stop treatment, because the consequences could be severe,” says Palti, although one patient whose cancer has disappeared has stopped wearing the device. Patients must go to the clinic twice a week to have their heads shaved so that their hair doesn’t interrupt contact between the scalp and the electrodes. The device itself costs only about $1,000 to manufacture, but replacing the electrodes twice a week is expensive.
Engelhard says that he got involved with the NovoCure clinical trial because the electric-field treatment is “radically different” from all existing cancer treatments. For patients with recurrent glioblastoma and other deadly forms of cancer, there are few options. “Researching and testing new therapies for this type of patient is very important,” says Engelhard.