Special Electric Signals Attack Cancer Cells with Lethal Force and Accuracy

NCI CAM Annual Report-FY10

Directing X-ray energy into the body has been a mainstay of cancer therapy since early in the 20th century, but an entirely different approach using electric pulses now shows great promise. The first research center in the United States devoted to this burgeoning field of electroporation (EP) was established about a decade ago at Old Dominion University in Norfolk, Virginia, where Andrei G. Pakhomov, Ph.D., currently works as a research associate professor in cell biology and biophysics.

“The idea is to deliver electric pulses of extremely short duration through an electrode directly to a tumor,” Dr. Pakhomov explained. If the pulses last only a matter of nanoseconds (a few billionths of a second), they create an electric field that blows open pores in the cellular membrane and disrupts the internal workings of the cell.

Nanosecond electrical pulses (nsEP) are bad news for the cancer cell in a many ways, Dr. Pakhomov noted. For example, the cellular membrane normally balances electrically charged molecules inside and outside the cell, but when the pores open up, the cell loses control of what’s going in and out. This change in the permeability of the membrane leads to osmotic imbalance, where “ions pour into the cell, followed by water, you get swelling, and more swelling until they eventually explode,” he added. “This is a form of necrotic cell death.”

The good news for cancer researchers is that killing cells by high-power electric pulses is virtually without side effects, because the intervention is carefully delivered directly to the tumor site and has little effect on nearby tissue, Dr. Pakhomov said. Other researchers have shown that a single treatment using nsEPs has killed melanoma cells in mice. The exciting results from such early work has made many researchers eager to further test nsEPs in animals and eventually in people.

However, researchers still need to figure out many of the details about how nsEP works and how the electric pulses might be modified to match their targets. “I think that we’re going to find different mechanisms for different kinds of cancer,” he explained, “because nsEPs have the power to cause both apoptotic and necrotic damage.”

Apoptosis – also known as programmed cell death – is a housekeeping process that cleans out unwanted cells by interfering with various cell survival functions. Many cancer cells are resistant to this process, leading researchers to develop drugs and therapies that induce apoptosis in various ways. “Apoptotic death is very clean,” Dr. Pakhomov continued, “with less pain and inflammation [to the patient] and no scarring. We can control nsEPs very precisely to induce apoptosis when we want, but some researchers maintain that the immune reaction is actually an important part of the fight against cancer.”

Dr. Pakhomov’s NCI-funded work* is laying the groundwork for a therapy that clinicians will be able to adapt according to the type of cancer they are targeting. By altering the characteristics of the electrical pulse (such as pulse width, voltage, and duration of the pulse train), the signal can be tailored to the target tissue. This is important, he said, because preliminary studies have shown that, while most cancers are vulnerable to nsEPs, they differ in how resistant they are, and at what point in their basic cell cycle they are most vulnerable. He foresees a time when the pulse delivery system will be sophisticated enough to allow doctors to create a mix of pulses that will target different types of tumor tissue at different times and with a combination of certain drugs.