Abstract
The temperature-independent effects of electromagnetic fields (EMF) have been controversial for decades. Here, we critically analyze the available literature on non-thermal effects of radiofrequency (RF) and microwave EMF. We present a literature review of preclinical and clinical data on non-thermal antiproliferative effects of various EMF applications, including conventional RF hyperthermia (HT, cRF-HT). Further, we suggest and evaluate plausible biophysical and electrophysiological models to decipher non-thermal antiproliferative membrane effects. Available preclinical and clinical data provide sufficient evidence for the existence of non-thermal antiproliferative effects of exposure to cRF-HT, and in particular, amplitude modulated (AM)-RF-HT. In our model, transmembrane ion channels function like RF rectifiers and low-pass filters. cRF-HT induces ion fluxes and AM-RF-HT additionally promotes membrane vibrations at specific resonance frequencies, which explains the non-thermal antiproliferative membrane effects via ion disequilibrium (especially of Ca2+) and/or resonances causing membrane depolarization, the opening of certain (especially Ca2+) channels, or even hole formation. AM-RF-HT may be tumor-specific owing to cancer-specific ion channels and because, with increasing malignancy, membrane elasticity parameters may differ from that in normal tissues. Published literature suggests that non-thermal antiproliferative effects of cRF-HT are likely to exist and could present a high potential to improve future treatments in oncology.
Highlights
Conventional radiofrequency (RF) hyperthermia (HT, cRF-HT) or microwave (MW) HT has been evaluated in clinical studies [1] and is used in the treatment of soft tissue sarcoma in combination with neoadjuvant chemotherapy [2], and for the treatment of cervical cancer [3,4,5] and superficial tumors [6,7,8,9], when combined with radiation therapy (RT)
The researchers applied clinical systems like mEHT. These studies have in common according to the general understanding of hyperthermia that temperature increases are below 40 C and the observed effects are to be regarded as non-thermal
Clinical and preclinical data suggest the existence of antiproliferative non-thermal effects (Sections 3 and 4), which can damage tumor cells at lower temperatures (
Summary
Conventional radiofrequency (RF) hyperthermia (HT, cRF-HT) or microwave (MW) HT has been evaluated in clinical studies [1] and is used in the treatment of soft tissue sarcoma in combination with neoadjuvant chemotherapy [2], and for the treatment of cervical cancer [3,4,5] and superficial tumors [6,7,8,9], when combined with radiation therapy (RT). The researchers applied clinical systems like mEHT (modulated electro-hyperthermia [23,24], TTF (tumor treating fields) [25] and the TheraBionic device [26,27]. These studies have in common according to the general understanding of hyperthermia that temperature increases are below 40 C and the observed effects are to be regarded as non-thermal. We hypothesize that additional non-thermal effects of the electromagnetic fields (EMF) exist and are clinically validated This hypothesis is controversial as it challenges current textbook knowledge and has a high potential to impact clinical practice. We summarize the current information regarding the non-thermal effects of EMF
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