Tumor Fighting Skullcap NovoTTF-100A System

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Glioblastoma, also known as Glioblastoma multiforme (GBM), is the most aggressive and malignant type of primary brain tumor, affecting 200,000 people in the US per year [3]. The average Glioblastoma survival rate with surgery and chemotherapy drugs is about 15 months, but a mere 4.5 months without treatment [4]. Using a novel wearable device, University of Virginia School of Medicine researchers completed a clinical trial in which median survival rates for people with Glioblastoma increased to 19.6 months, with 43%of users surviving for more than 2 years [1].  The device in the study, the Novocure Tumor Treating Fields (TTF-100A) System, delivers 1-3 V/cm of electricity to the cells through a series of transducer arrays attached at the site of the tumor and charged by a portable battery. At low frequencies, the tissue is stimulated by depolarizing the membrane of the cells. This electrical stimulation disrupts the mitotic processes of cells, forcing the tubulin subunits active in mitosis to align with the electric field rather than the spindle fibers in metaphase, subsequently, this disruption causes apoptosis in anaphase. The development and use of Tumor Treating Fields as a form of therapy is greatly beneficial for those diagnosed with Glioblastoma, as molecularly targeted drug delivery systems are not permeable across the protective protein junctions of the Blood Brain Barrier (BBB). Clinical studies demonstrate that use of TTF is comparable in efficacy to that of chemotherapy, with a preferential safety profile and fewer toxic side effects. The FDA has approved TTF technology for the treatment of recurrent glioblastomas ; for newly diagnosed Glioblastoma, surgery remains the standard of care [2]. 

 

Cells experiencing moderate to severe membrane blebbing (bubbling that occurs as cell detaches its cytoskeleton from the membrane, indicative of apoptosis) as a result of TTF (Davies et. al, 2013).

References

  1. Barney, Josh. "Wearable Device Slows Deadly Brain Tumors, Clinical Trial Finds." Wearable Device Slows Deadly Brain Tumors, Clinical Trial Finds. University of Virginia, 8 Apr. 2015. Web. 28 Oct. 2015.
  2. Davies, Angela M., Uri Weinberg, and Yoram Palti. "Tumor Treating Fields: A New Frontier in Cancer Therapy." Ann. N.Y. Acad. Sci. Annals of the New York Academy of Sciences 1291.1 (2013): 86-95. Web.
  3. Bleeker, Fonnet E., Remco J. Molenaar, and Sieger Leenstra. "Recent Advances in the Molecular Understanding of Glioblastoma." J Neurooncol Journal of Neuro-Oncology 108.1 (2012): 11-27. Web.
  4. Johnson, Derek R., and Brian Patrick O’Neill. "Glioblastoma Survival in the United States before and during the Temozolomide Era." J Neurooncol Journal of Neuro-Oncology 107.2 (2011): 359-64. Web.

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The NovoTTF-100A System is particularly advantageous for use in glioblastoma treatment as it allows the drugs necessary for treatment to permeate the BBB. This form of therapy can also be used to treat brain metastases, lung cancer, ovarian cancer, and pancreatic cancers. TTF voltage and frequency can be manipulated to optimize treatment effectiveness for various types of tumors. Additionally, dividing cancer cells have different frequency requirements for mitotic interference than healthy cells, decreasing the risk of healthy cell death, one of the major side effects of chemotherapy [2]. 

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TTF does not attenuate through biological tissues or over distance; the transducer arrays are noninvasive and can be easily removed for daily activities such as showering. The only recorded side effects of TTF are topical skin rashes caused by electrode application. However, due to the system design in which glioblastoma patients have to shave their head to attach the electrodes and carry a laptop-sized portable battery, clinical trials have reported an issue in patient compliance with treatment.  So while there may be nothing fundamentally wrong with the technology, ensuring that patients will use the treatment is emerging as a critical obstacle to treatment success. 

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