Tumor Treating Fields: At the Crossroads Between Physics and Biology for Cancer Treatment

Abstract

Despite extraordinary advances that have been achieved in the last few decades, cancer continues to represent a leading cause of mortality worldwide. Lethal cancer types ultimately become refractory to standard of care approaches; thus, novel effective treatment options are desperately needed. Tumor Treating Fields (TTFields) are an innovative non-invasive regional anti-mitotic treatment modality with minimal systemic toxicity. TTFields are low intensity (1-3 V/cm), intermediate frequency (100-300 kHz) alternating electric fields delivered to cancer cells. In patients, TTFields are applied using FDA-approved transducer arrays, orthogonally positioned on the area surrounding the tumor region, with side effects mostly limited to the skin. The precise molecular mechanism of the anti-tumor effects of TTFields is not well-understood, but preclinical research on TTFields suggests it may act during two phases of mitosis: at metaphase, by disrupting the formation of the mitotic spindle, and at cytokinesis, by dielectrophoretic dislocation of intracellular organelles leading to cell death. This review describes the mechanism of action of TTFields and provides an overview of the most important in vitro studies that investigate the disruptive effects of TTFields in different cancer cells, focusing mainly on anti-mitotic roles. Lastly, we summarize completed and ongoing TTFields clinical trials on a variety of solid tumors.

The Routine Application of Tumor-Treating Fields in the Treatment of Glioblastoma WHO° IV

“…This method is based on the local effect of electric fields to interfere with the mitotic activity of the tumor. Proliferating cells are blocked in metaphase and anaphase as the formation of the mitotic spindle is disturbed, which results in slower cell replication or apoptosis ( 11 – 14 ).…”

Healing Field: Using Alternating Electric Fields to Prevent Cytokine Storm by Suppressing Clonal Expansion of the Activated Lymphocytes in the Blood Sample of the COVID-19 Patients

“…Alternating electric field (AEF) therapy, mostly called tumor-treating fields (TTF), is a safe treatment of highly proliferative cancer cells by delivering the low intensity and intermediate frequency electric field ( Carrieri et al, 1991 ; Hottinger et al, 2016 ). The method disrupts the mitotic spindle assembly of the dividing cells ( Kirson et al, 2007 ).…”

The Biological and Molecular Function of LINC00665 in Human Cancers

“…According to statistical estimations from 185 countries, there were more than 18 million new cancer cases and almost 10 million cancer-related deaths in 2018 ( 1 ). Although numerous treatment strategies for cancers have been developed and improved, including classical therapies (surgery, radiotherapy, and chemotherapy) and immune and molecular targeted therapies, the therapeutic effects remain unsatisfactory ( 2 , 3 ). Thus, there is an urgent need to explore valuable targets and novel biomarkers for cancer therapy, diagnosis, and prognostic evaluation.…”