Electric Fields Have Potential as a Cancer Treatment

Low-intensity electric fields can disrupt the division of cancer cells and slow the growth of brain tumors, according to recent laboratory studies and a small human trial, suggesting that electric fields may become a new weapon for stalling the progression of cancer.

The research, performed by an international team of researchers, led by Dr. Yoram Palti, from the Technion - Israel Institute of Technology (Haifa, Israel), was published in the August 2007 issue of Physics Today. In the study, the researchers utilized alternating electric fields that rattle electrically charged particles in cells back and forth hundreds of thousands of times per second. The electric fields have an intensity of only one or two volts per centimeter. Such low-intensity alternating electric fields were once thought to do nothing significant other than heat cells.

However, in several years' worth of experiments, the researchers demonstrated that the fields disrupt cell division in tumor cells placed on a glass dish (in vitro). After intensively studying this effect in vitro and in laboratory animals, the researchers initiated a small human clinical trial to evaluate its cancer-fighting ability. The technique was then applied to 10 human patients with recurrent glioblastoma multiforme (GBM), a form of brain cancer with a very low survival rate. All the patients had their earlier tumors treated by other methods, but the cancer had started to recur in all cases.

Fitting the patients with electrodes that applied 200 kHz electric fields to the scalp at regular intervals for up to 18 hours per day, the researchers observed that the brain tumors progressed to advanced stages much slower than was typical (taking a median time of 26 weeks), and sometimes even regressed. The patients also lived considerably longer, with a median survival time of 62 weeks.

While no control group existed, the findings compared favorably to historical data for recurrent GBM, in which the time for tumor progression is approximately 10 weeks and the typical survival time is 30 weeks. Moreover, three of the 10 patients were still alive two years after the electrode therapy was initiated. These results were published in the June 12, 2007, issue of the Proceedings of the [U.S.] National Academy of Sciences (PNAS).

The Physics Today article reported these results in terms of the physical processes that enable the electric fields to affect dividing cancer cells. In vitro, the electric fields were seen to have two effects on the tumor cells.

First, they hampered cell division. Cells that typically took less than one hour to divide were still not completely divided after three hours of exposure to an electrical field of 200 kHz. Another group of researchers at the Cleveland Clinic (Cleveland, OH, USA) slowed cell division by applying electric fields with a much lower frequency of only 50 Hz. Furthermore, this protocol demonstrated the ability to decrease the intrinsic drug resistance of the cells.

What causes cell division to slow down in the 200-kHz case is this: the electric fields suppress the formation and function of a major cell structure known as the mitotic spindle. The spindle is composed of cell components known as microtubules. The microtubules in turn contain components that have a high electric dipole moment, in which there is a large separation of opposite electric charges. Therefore, parts of the mitotic spindle are greatly influenced, and apparently disrupted, by an electric field.

The second effect of the 200 kHz fields is that they sometimes disintegrated the daughter cells just before they split off from their partners. The dividing cells occasionally destruct because a high-electric-field region develops between the two daughter cells. This leads to a large slope, or gradient, in the electric field from each daughter cell to this region. This gradient may pull organelles (cell structures) and macromolecules (such as proteins) from the scaffolding of the cells.

The alternating electric fields are believed to have similar effects in human glioblastomas. In contrast, the electric-field treatment poses little danger to normal brain tissue, because healthy brain cells do not divide. The electric fields were only observed to have disruptive effects on dividing cells.

Based on the success of their initial human study, the researchers are working on another human clinical trial, this time with a control group receiving chemotherapy. The researchers are also assessing the possibility of combining electric-field therapy with low-dose chemotherapy.


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Technion - Israel Institute of Technology