Alternating electric field therapy
Alternating electrical fields can disrupt mitosis leading to apoptosis of rapidly dividing cancer cells. The device that utilizes this mechanism is known as tumor-treating fields (TTFields).
The anti-tumor mechanism of tumor treating fields (TTFields) is mainly through interfering with the dynamics of microtubule subunits in mitosis,which blocks the normal process of cell division and eventually leads to cell death.In recent years,relevant studies have found that TTFields still have immunological,molecular biological and other related anti-tumor mechanisms,and can induce reversible increase of cell membrane and blood-brain barrier permeability,which plays a synergistic role in combination with anti-tumor drugs.With the development of multi-system research,the specific treatment frequency,time and field strength of TTFields in different tumor treatments will be revealed.These research progress will further expand the application field of TTFields and benefit more patients 1).
Finite element (FE) methods are used to calculate the intensity of TTFields as a measure of therapeutic “dose.” However, the antitumor efficacy also depends on the direction and exposure time of the induced fields.
Korshoej et al. proposed a new FE approach for TTFields dosimetry that incorporates all these parameters in order to estimate both the unwanted directional field correlation (fractional anisotropy, FA) and the average field intensity. The method uses singular value decomposition to decompose the sequential TTFields over one duty cycle into principal components. Using this method, they showed that significant unwanted FA occurs in many brain regions, potentially affecting therapeutic efficacy. The distribution of FA in the brain varies between different transducer array layouts, and in fact the FA estimate indicates a different order of array performance than predicted from the more conventional estimate of field intensity. Furthermore, they found that resection of the tumor tends to nullify field distribution differences between array layouts while also significantly increasing FA. Contrary to the current practice, these results suggest that it may be more effective to place the TTFields arrays to maximize the field intensity in the tumor, rather than trying to maintain macroscopic orthogonality between the layout pairs. This principal component analysis framework has a number of potential applications, including technology development, outcome prognostication, improved treatment planning, and activation cycle optimization. They descibed the framework for the principal component calculations and recapitulates the current results. Furthermore, it provides a detailed outline of how patient-specific head models can be used to calculate the field distribution for individual patients 2).
Lei et al. co-cultured cancer cells and normal cells to investigate the selectivity and chemosensitivity enhancement of an electric field treatment. Cancer cells (cell line: HeLa and Huh7) and fibroblasts (cell line: HEL299) were cultured in an in-house-developed cell culture device embedded with stimulating electrodes. A low-intensity alternating electric field was applied to the culture. The field significantly induced proliferation arrest of the cancer cells, while had limited influence on the fibroblasts. Moreover, in combination with the anti-cancer drug, damage to the cancer cells was enhanced by the electric field. Thus, a lower dosage of the drug could be applied to achieve the same treatment effectiveness. This study provides evidence that low-intensity electric field treatment selectively induced proliferation arrest and enhanced the chemosensitivity of the cancer cells. This electro-chemotherapy could be developed and applied as a regional cancer therapy with minimal side effects 3).
The goal of Carlson et al. was to uncover the mechanism underlying tumour-treating fields’ efficacy in killing cancer cells. Modelling the effects of these 200 kHz alternating current electric fields on tumour cell sub-structures has led us to focus on the microtubules (MTs), C-termini and the motor protein kinesin, which are integral to the critical functions of MT transport of proteins during the delicate orchestration of cell division (mitosis). Leading hypotheses of the TTFields’ mechanism that we are modelling include disruption of mitosis functions (such as the ‘kinesin walk’ along MTs), C-termini state transitions and MT polymerization 4).