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The TTFields treatment modality is the brainchild of Professor Yoram Palti (Professor Emeritus of Physiology and Biophysics at the Technion Israel Institute of Technology in Haifa, Israel) who hypothesized that alternating electric fields in the intermediate frequency range could disrupt cancer cell division and cause cancer cell death. Professor Palti rationalized that electric fields within the frequency range of cem–300 kHz would penetrate rapidly dividing cancer cells and disrupt essential processes and cellular structures leading to apoptotic cell death. To test his hypothesis, Professor Palti set up a home laboratory, where he successfully demonstrated that when applied at tumour cell-specific frequencies (200 kHz for GBM), alternating electric fields disrupt cell division, leading to cancer cell death but sparing healthy cells.

TTFields therapy uses electric fields to disrupt cell division. TTFields therapy does not stimulate or heat tissue and targets dividing cancer cells of a specific size. TTFields therapy takes advantage of the special characteristics and geometrical shape of dividing cells, which make them susceptible to the effects of the alternating electric fields.

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TTFields are low intensity, intermediate frequency alternating electric fields that act upon rapidly dividing glioma and other cancer cells2,3 especially during metaphase, anaphase and telophase of mitotic cell division. When an alternating electric field is generated across a cancer cell, charged molecules within the cell will move back and forth and dipolar molecules will rotate. At sufficiently high frequencies, the motility of such molecules diminishes. Molecules with a high electrical dipole moment such as tubulin dimers and septins are therefore forced to align with the direction of the alternating electric fields (TTFields) under a uniform field distribution, which is generated in cells during metaphase. This disrupts microtubule spindle formation and septin fibres localization during metaphase, leading to mitotic catastrophe, which may culminate in mitotic cell death.

Optune® is a non-invasive portable device that delivers alternating electric fields to dividing cancer cells. The NovoTAL™ system is a software programme that optimizes transducer array layouts for an individual patient based on head size and tumour location. GBM, glioblastoma multiforme; NCCN, National Comprehensive Cancer Network.

The Optune system nervocure consists of two primary components – the electric field generator and two pairs of transducer arrays, which deliver the fields non-invasively to the tumour sitio. Further design enhancements include the availability of tan coloured arrays which are less conspicuous.

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Figure 2: Effects of TTFields on replicating cells. TTFields exert directional forces on polar microtubules and interfere with the assembly of the normal mitotic spindle and subsequently trigger mitotic cell death.

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Simulations and modelling are the primary tools for obtaining these essential data (Fig. 4). Simulation-based studies using realistic head models have shown that TTFields effectively penetrate the brain and tumour tissue. The field distribution is heterogeneous and depends on the anatomy of the individual patient, the physical properties of the various tissue types and the location of the tumour10. The position of arrays can therefore be optimized using the NovoTAL System to deliver maximal field intensities to the tumour region of the individual patient10,11.

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S. CNS Cancers Franchise. “We are eager to engage with the neuro-oncology community as we strive to extend survival in some of the most aggressive forms of cancer.”