Tumor Treating Fields

Diagnostics

Electric field therapy is a non-invasive method of tumor treatment that uses alternating electric fields of specific frequency and intensity to selectively destroy mitosis in cancer cells. Electric field therapy can target proteins that are critical to the cancer cell cycle, leading to mitotic arrest, which can cause apoptosis in cancer cells and activate the patient’s own anti-tumor immune response. Electric field therapy has been approved by the FDA for new diagnostic and recurrent gliomas. Experiments with other local solid tumors are ongoing.

Figure 1. Model for TTFields leading to mitotic disruption.

The principle of electric field therapy can be explained by two basic physical principles: dipole permutation and dielectrophoresis. Simply put: one of the biggest features of tumor cells is uncontrolled cell division. Cell division is closely related to the nanoscale biomolecular behavior during the periodic formation and destruction of microtubule polymers. Microtubule polymers are formed by tubulin dimers with highly polarized properties, and they are very sensitive for the external electric field. An external electric field of appropriate intensity and frequency is generated by a non-contact capacitive electrode placed near the tumor, which can interfere with tumor cell division and ultimately destroy the tumor cells.

The unique principle of electric field therapy gives it a special killing effect on cancer cells: 1. It can treat deep tumors. The electric field therapy is non-uniformly distributed throughout the treatment area, covering the geometry of all treatment sites, and the transducer arrays are not attenuated and can therefore be used to treat tumors located deep. 2. Sustainable treatment. Since the electric field does not have a half-life, the electric field is continuously delivered during the treatment. 3. Precise targeting prevents cancer cell division. The electric field can selectively interfere with the cancer cells in the fast-growth mitotic phase that produce highly charged substances, causing them to enter the cell suicide program death, but have no significant effect on the normal cells of the quiescent and dividing phases. 4. Safe and non-invasive. So far, since electric field therapy has no effect on normal cell division, no related adverse events of electric field treatment have been reported. The main side effect is skin irritation. Prevention strategies include proper shaving, cleaning the scalp and frequent replacement of the electrode patch. When skin problems occur, it is usually possible to change the placement of the patch or using oral antibiotics, or corticosteroids. 5. Therapeutic equipment for electric field therapy. Electric field therapy consists of attaching a patient’s non-invasive transducer array and an extracorporeal generator to deliver an electric field through the skin.

In the development of tumor electric field therapy, test and labeling for changes in tubulin are involved, for example, microtubule-labeled antibodies are used to label microtubules, and changes in microtubule formation in tumor cells before and after electric field treatment are observed. In addition, a mitotic marker (phosphorylated histone 3) is also necessary to reflect the effect of the electric field on mitosis. For the study of the final therapeutic effect, the researchers need tumor cell marker antibodies and cell death marker antibodies (Annexin V) to show the specific killing efficiency of the electric field on cancer cells.

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