User:Novafields/Alternating electric field therapy

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Alternating electric field therapy, sometimes called tumor treating fields (TTFields), is a type of electromagnetic field therapy using low-intensity, intermediate frequency electrical fields to treat cancer. TTFields disrupt cell division by disrupting dipole alignment and inducing dielectrophoresis of critical molecules and organelles during mitosis. The use of TTFields is approved in the United States and Europe for the treatment of newly diagnosed and recurrent glioblastoma multiforme (GBM), and is undergoing clinical trials for several other tumor types.

something about Novocure?

TTField-generating device manufactured by the Israeli company Novocure Despite earning regulatory approval, the efficacy of this technology remains controversial among medical experts.

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Mechanism

All living cells contain polar molecules and will respond to changes in electric fields. Alternating electric field therapy, or Tumor Treating Fields (TTFields) use insulated electrodes to apply very-low-intensity, intermediate-frequency alternating electrical fields to a target area containing cancerous cells. Polar molecules play a key role in cell division, making mitosis particularly susceptible to interference from outside electric fields. TTFields disrupt dipole alignment and induce dielectrophoresis during mitosis, killing proliferating cells.

Dipole Alignment Polar molecules critical to mitosis include α/β-tubulin and the septin heterotrimer. Tubulin is necessary for mitotic spindle formation during metaphase, while septins stabilize the cell during cytokinesis. When exposed to TTFields, these molecules align their dipole with the electric field, freezing them in one orientation. This prevents tubulin and septin molecules from moving to and binding where they are needed for successful cell division. This results in mitotic catastrophe, initiating cell death through apoptosis. Uneven chromosome splitting can also be a result of TTFields' affect on dipole alignment, resulting in daughter cells with abnormal chromosome numbers. Dielectrophoresis

Cells that successfully complete metaphase are later susceptible to TTFields during telophase. At this stage in cell division, the cell takes on an hourglass shape as it prepares to divide in two. This results in a non-uniform electric field within the cell, with high field density at the cell's furrow. This causes polar molecules and organelles to migrate with the electric field toward the furrow. This disrupts the cell's division and leads to cell death.

In principle, this approach could be selective for cancer cells in regions of the body, such as the brain, where the majority of normal cells are non-proliferating. The frequency of the TTField can be adjusted between 100 and 300kHz to target cancer cells and avoid harming healthy cells.  Current research supports that cell size is inversely proportional to optimal TTField frequency. TTFields can also be optimized by orienting two transducer arrays perpendicular to each other to maximize the amount of cells that will be affected. Cells divide in different orientations and are most affected by an electric field that is parallel to their direction of division (perpendicular to the mitotic plate). Clinicians determine where to place the transducer arrays to optimize treatment using software that analyzes tumor location and the patient's morphometry. Emerging evidence suggests that alternating electric field therapy disrupts various biological processes, including DNA repair, cell permeability and immunological responses, to elicit therapeutic effects. Greater mechanistic understanding of TTFields may pave the way for new, more effective TTFields-based therapeutic combinations in the future.

Medical Uses

Recurrent Glioblastoma

Newly Diagnosed Glioblastoma

Recurrent Ovarian Carcinoma

Medical Device

Side Effects

Regulatory Approval

Company