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Review

Modulated Electro-Hyperthermia-Induced Tumor Damage Mechanisms Revealed in Cancer Models

1
Department of Pathology and Experimental Cancer Research, Semmelweis University, H-1085 Budapest, Hungary
2
Institute of Oncology at 1st Department of Internal Medicine, Semmelweis University, H-1083 Budapest, Hungary
3
Institute of Translational Medicine, Semmelweis University, H-1094 Budapest, Hungary
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(17), 6270; https://doi.org/10.3390/ijms21176270
Received: 15 July 2020 / Revised: 22 August 2020 / Accepted: 24 August 2020 / Published: 29 August 2020
The benefits of high-fever range hyperthermia have been utilized in medicine from the Ancient Greek culture to the present day. Amplitude-modulated electro-hyperthermia, induced by a 13.56 MHz radiofrequency current (mEHT, or Oncothermia), has been an emerging means of delivering loco-regional clinical hyperthermia as a complementary of radiation-, chemo-, and molecular targeted oncotherapy. This unique treatment exploits the metabolic shift in cancer, resulting in elevated oxidative glycolysis (Warburg effect), ion concentration, and electric conductivity. These promote the enrichment of electric fields and induce heat (controlled at 42 °C), as well as ion fluxes and disequilibrium through tumor cell membrane channels. By now, accumulating preclinical studies using in vitro and in vivo models of different cancer types have revealed details of the mechanism and molecular background of the oncoreductive effects of mEHT monotherapy. These include the induction of DNA double-strand breaks, irreversible heath and cell stress, and programmed cells death; the upregulation of molecular chaperones and damage (DAMP) signaling, which may contribute to a secondary immunogenic tumor cell death. In combination therapies, mEHT proved to be a good chemosensitizer through increasing drug uptake and tumor reductive effects, as well as a good radiosensitizer by downregulating hypoxia-related target genes. Recently, immune stimulation or intratumoral antigen-presenting dendritic cell injection have been able to extend the impact of local mEHT into a systemic “abscopal” effect. The complex network of pathways emerging from the published mEHT experiments has not been overviewed and arranged yet into a framework to reveal links between the pieces of the “puzzle”. In this paper, we review the mEHT-related damage mechanisms published in tumor models, which may allow some geno-/phenotype treatment efficiency correlations to be exploited both in further research and for more rational clinical treatment planning when mEHT is involved in combination therapies. View Full-Text
Keywords: modulated electro-hyperthermia; irreversible cell stress; apoptosis; damage signaling; immunogenic cell death modulated electro-hyperthermia; irreversible cell stress; apoptosis; damage signaling; immunogenic cell death
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MDPI and ACS Style

Krenacs, T.; Meggyeshazi, N.; Forika, G.; Kiss, E.; Hamar, P.; Szekely, T.; Vancsik, T. Modulated Electro-Hyperthermia-Induced Tumor Damage Mechanisms Revealed in Cancer Models. Int. J. Mol. Sci. 2020, 21, 6270. https://doi.org/10.3390/ijms21176270

AMA Style

Krenacs T, Meggyeshazi N, Forika G, Kiss E, Hamar P, Szekely T, Vancsik T. Modulated Electro-Hyperthermia-Induced Tumor Damage Mechanisms Revealed in Cancer Models. International Journal of Molecular Sciences. 2020; 21(17):6270. https://doi.org/10.3390/ijms21176270

Chicago/Turabian Style

Krenacs, Tibor, Nora Meggyeshazi, Gertrud Forika, Eva Kiss, Peter Hamar, Tamas Szekely, and Tamas Vancsik. 2020. "Modulated Electro-Hyperthermia-Induced Tumor Damage Mechanisms Revealed in Cancer Models" International Journal of Molecular Sciences 21, no. 17: 6270. https://doi.org/10.3390/ijms21176270

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