TTFields therapy demonstrates that non-ionizing radiation can have biological effects beyond just heating. It specifically targets rapidly dividing cancer cells by disrupting their growth and division processes. The reason TTFields therapy can have an impact on cells is due to its unique frequency, intensity, and application method, which are tailored to affect cancer cells more selectively.
It is important to note that TTFields therapy operates in a specific frequency range (100-300 kHz) and at low power levels (1-3 W/m²), which are different from the RF waves emitted by wireless devices. The frequencies and power levels used in TTFields therapy have been carefully selected to optimize their effect on cancer cells while minimizing side effects on healthy cells and tissues.
While TTFields therapy highlights that non-ionizing radiation CAN have biological effects beyond heating, it does not necessarily imply that all non-ionizing radiation is harmful. The potential health risks of non-ionizing radiation depend on factors such as frequency, intensity, exposure duration, and the specific biological system in question.
In TTFields therapy, alternating electric fields with intermediate frequencies are used. For glioblastoma treatment, a frequency of 200 kHz has been shown to be effective. These specific frequencies have been selected because they can disrupt the growth and division of cancer cells while causing minimal damage to healthy cells. The exact frequency may vary for different types of cancer, as the optimal frequency depends on the specific characteristics of the cancer cells being targeted.
TTFields, or Tumor Treating Fields, are a non-invasive cancer treatment that uses alternating electric fields to disrupt the growth and division of cancer cells, particularly in glioblastoma, a type of aggressive brain tumor. The electric fields are generated by a portable device and applied to the patient’s shaved scalp using an array of ceramic electrodes. TTFields therapy is administered continuously for at least 18 hours per day, and it is often used in combination with other treatments, such as chemotherapy, surgery, and radiation therapy.
The mechanism behind the therapeutic effect of TTFields is not yet fully understood, but several proposed mechanisms include:
- Dielectrophoresis of cellular components: TTFields may cause dielectrophoretic forces on polarizable particles within the cell, such as organelles and macromolecules. These forces can lead to the misalignment of critical cellular structures, such as the mitotic spindle, and disrupt cell division.
- Disturbance of the spindle apparatus: TTFields have been shown to interfere with the proper alignment of the mitotic spindle during cell division, leading to the formation of abnormal daughter cells and subsequent cell death.
- Plasma membrane perforation: TTFields may induce the formation of small pores in the plasma membrane, leading to the leakage of cellular contents and subsequent cell death.
Recent studies suggest that voltage-gated ion channels (VGICs) might be key targets for TTFields therapy. VGICs are transmembrane proteins that regulate the flow of ions across the cell membrane in response to changes in the membrane potential. They play critical roles in various cellular processes and may be involved in cancer development and progression. Since VGICs are sensitive to changes in the electric field, they could potentially act as transducers between electric fields and biological responses, making them possible targets for TTFields therapy.
The patient carries a portable device that generates the electric fields, and the treatment is applied continuously for at least 18 hours per day. TTFields therapy has shown an increase in progression-free survival and overall survival when added to standard treatment (Stupp et al., 2017). However, the molecular mechanism behind the therapeutic effect of TTFields is not yet fully understood.
2.1. Proposed mechanisms of action of TTFields Several mechanisms have been proposed to explain the anti-tumor effects of TTFields, including:
- Dielectrophoresis of cellular components: TTFields may exert their effects by inducing dielectrophoretic forces on polarizable particles within the cell, such as organelles and macromolecules. These forces can lead to the misalignment of critical cellular structures, such as the mitotic spindle, and disrupt cell division (Kirson et al., 2004; Tuszynski et al., 2016).
- Disturbance of the spindle apparatus: TTFields have been shown to interfere with the proper alignment of the mitotic spindle during cell division, leading to the formation of abnormal daughter cells and subsequent cell death (Kirson et al., 2004; Gera et al., 2015).
- Plasma membrane perforation: TTFields may induce the formation of small pores in the plasma membrane, leading to the leakage of cellular contents and subsequent cell death (Golberg et al., 2016; Miklavčič et al., 2016).
Despite these proposed mechanisms, the direct molecular targets of TTFields remain elusive. Recent studies suggest that voltage-gated ion channels (VGICs) might be key targets for TTFields therapy.
- Voltage-gated ion channels as molecular targets of TTFields Voltage-gated ion channels are transmembrane proteins that regulate the flow of ions across the cell membrane in response to changes in the membrane potential. They play critical roles in various cellular processes, such as action potential generation, muscle contraction, and hormone secretion. Accumulating evidence suggests that VGICs may be involved in cancer development and progression, making them potential targets for cancer therapy (Prevarskaya et al., 2018).
3.1. VGICs as transducers of electromagnetic fields VGICs are equipped with voltage-sensing domains, which are sensitive to changes in the membrane potential. These voltage sensors can be influenced by external electric fields, such as those generated by TTFields. In certain fish species, specialized electroreceptor organs containing VGICs are capable of detecting weak electric fields in their environment (Baker et al., 2015; Bellono et al., 2017). This suggests that VGICs may function as transducers between electric fields and biological responses, making them possible targets for TTFields therapy.
3.2. Modulation of ion channel function by external electromagnetic fields Several studies have reported the effects of external electromagnetic fields on the function of ion channels. For example, weak electric fields have been shown to modulate the activity of various ion channels, such as the voltage-gated Na+ and K+ channels, the hyperpolarization-activated cyclic nucleotide-gated channels, and the transient receptor potential channels (Levin and Korenstein, 1991; Amzica and Steriade, 1995; D’Andrea et al., 2013; Cervellati et al., 2014; Osera et al., 2015).
In the context of cancer therapy, ion channel modulation by external electromagnetic fields may have potential therapeutic benefits. For instance, TTFields have been shown to inhibit the activity of voltage-gated K+ channels in glioblastoma cells (Li et al., 2020).
Full Report https://www.frontiersin.org/articles/10.3389/fncel.2023.1133984/full
- “Voltage-Gated Ion Channels: A Potential Target for TTFields Cancer Therapy”
- “Understanding the Mechanisms Behind Tumor Treating Fields Therapy”
- “VGICs as Transducers of Electromagnetic Fields in Cancer Therapy”
- “The Promise of Ion Channel Modulation in Non-Invasive Cancer Treatment”
- “TTFields Therapy: Disrupting Cancer Cell Growth with Alternating Electric Fields”
Twitter post: “New report sheds light on the mechanisms behind Tumor Treating Fields Therapy, a non-invasive cancer treatment that disrupts cancer cell growth with electric fields. Voltage-gated ion channels may be key targets for this therapy. Read more: [insert link] #cancertherapy #TTFields”
