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Electrifying Brain Tumors

Combined with chemotherapy, electric fields help prevent the growth of deadly brain tumors.

By Lauren Gravitz

Thursday, October 29, 2009

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The particularly lethal brain cancer known as glioblastoma multiforme is fast-growing, difficult to treat, and nearly always fatal; even with aggressive therapy, patients have a median survival time of less than two years. But scientists are pursuing new ways to attack this type of brain tumor, and one company may just be succeeding. NovoCure, a small startup founded in Israel in 2000, has developed a device that uses an electric field to disrupt the growth of cancer cells, and early results are promising. Out of ten patients who started using the device in combination with chemotherapy shortly after their initial diagnosis, seven are still alive more than four years later, and five of them show no signs of cancer progression.

Electrifying division: These images show skin melanoma cells at various stages of disrupted division. The process was fatally interrupted through the use of electrical fields.
Credit: NovoCure

NovoCure's device consists of insulated electrode pairs placed on a patient's body near the tumors, attached by leads to a three-kilogram battery that the patient carries everywhere. The electrodes emit low-intensity electric fields that rapidly alternate to create a current that has no effect on any tissue in the body except dividing cells. Just before a dividing cell splits in two, it briefly forms an hourglass shape before the two daughter cells pinch off, and this shape is particularly vulnerable to electricity. The current gets concentrated at the cell's narrow waist, and at the very moment of division, the cell membrane is destroyed, and the cells disintegrate.

Previous trials showed promising early results, first in patients with recurrent glioblastoma who had exhausted their treatment options, and then in patients newly diagnosed with the disease. The new results are so promising that the company is now recruiting 283 newly diagnosed glioblastoma patients across the United States and in Europe to participate in a two-year pivotal clinical trial. (The U.S. Food and Drug Administration approval process for medical devices requires only two clinical trial phases, pilot and pivotal, as opposed to the three required for medications.) Recent results from a pilot lung-cancer trial show that the combination of electric fields plus traditional chemotherapy may also increase survival and decrease disease progression in patients with late-stage non-small cell lung cancer.

While chemotherapy and the electric field generated by the device both have an effect when used in isolation, when they're put together their properties are more than additive--the electric fields appear to make the cancer cells far more susceptible to chemotherapy without any additional increase in side effects and toxicity.

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"Practically all chemotherapies are designed to hit specific receptors on cancer cells, and they are usually targeted to very specific types or even subtypes of cancer," says physiologist Yoram Palti, the founder and director of NovoCure, who developed the therapy. In contrast, he says, radiation hits all types of cancers, but its ability to target cancer cells over other tissues is relatively low. "I was looking for a single modality that would be effective against most, if not all, types of cancer, without the negative effects of radiation," Palti says. The electric field appears to do just that. "In the lab, it's effective against all types of cancer cells we tested."

Typical glioblastoma treatment consists of surgery followed by simultaneous chemotherapy and radiation. After about four weeks, radiation stops and chemotherapy continues. But the reason glioblastoma is so deadly is that cancerous cells spread throughout the brain long before they can be picked up by MRI scans. "The horses are already out of the barn, so to speak," says Herbert Engelhard, chief of neuro-oncology in the neurosurgery division at the University of Illinois, Chicago. "NovoCure therapy has the potential of tracking down or affecting those cancer cells that are deep within the brain, because the [electric field] goes beyond what is seen on the MRI imaging of the brain tumor."

Comments

  • Wonderful!
    On their web site (http://www.novocuretrial.com/), NovoCure provides an interesting video of cancer cells being disrupted during cell division,  References give the details of the frequency and voltage gradients used in tissue culture (http://www.biomedcentral.com/1756-6649/9/1): "As previously described [1,2], two pairs of electrodes, insulated by a high dielectric constant ceramic, were positioned normal to each other at a distance of 20 mm in treatment and control dishes. In the former, the electrodes were connected to sinusoidal waveform generator that generated fields of optimal frequencies in the medium [1,2,9]: 150 kHz for breast cancer and 200 kHz for glioma, that changed direction by 90° every 250 ms. Field intensity was measured as described previously [2] and expressed as V/cm. For 72 h experiments the TTFields intensity of 1.75 V/cm was used. For 24 h experiments 0.65, 1.25 and 1.75 V/cm TTFields were used."

    The ability to disrupt cells during division provides many interesting avenues of research.  Can the formation of capillaries in a tumor be prevented?  Can leukemic cells be destroyed?  What about protozoan parasites, can they be killed?  Many possibilities.
    Rate this comment: 12345

    cyberpageman
    10/29/2009
    Posts:37
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    4/5
  • orther cells
    The cancer isn't the only cell dividing in the brain. New neuron formation in the hippocampus aids in new memory formation. Glial cells also divide. So are these cells also killed in division? What are the side effects?
    Rate this comment: 12345

    hsfrey
    11/03/2009
    Posts:13
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    4/5
    • Re: orther cells
      Well, the article states the study shows no side effects in addition to the chemotherapy. Since the article says only half of patients have shown no progression of the cancer, clearly it's not killing all dividing cells, just most of them -- which is mostly going to be the cancer.
      Rate this comment: 12345

      Monsterboy
      11/10/2009
      Posts:89
      Avg Rating:
      4/5

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