Optimization of tumor-treating field therapy for triple-negative breast cancer cells in vitro via frequency modulation

Austin R Smothers; Jason R Henderson; John J O'Connell; Jonathan M Stenbeck; Delphine Dean; Brian W Booth

doi:10.1186/s12935-023-02959-x

Optimization of tumor-treating field therapy for triple-negative breast cancer cells in vitro via frequency modulation

Cancer Cell Int. 2023 Jun 7;23(1):110. doi: 10.1186/s12935-023-02959-x.

Authors

Austin R Smothers^{1

2}, Jason R Henderson³, John J O'Connell^{4

5

6}, Jonathan M Stenbeck⁴, Delphine Dean^{1

2}, Brian W Booth⁷

Affiliations

¹ Center for Innovative Medical Devices and Sensors (REDDI Lab), Clemson University, Clemson, SC, USA.
² Department of Bioengineering, Clemson University, Clemson, SC, USA.
³ Quiverent LLC, Greenville, SC, USA.
⁴ Prisma Health Cancer Institute, Prisma Health, Greenville, SC, USA.
⁵ Clemson University School of Health Research, Clemson, SC, USA.
⁶ University of South Carolina School of Medicine-Greenville, Greenville, SC, USA.
⁷ Department of Bioengineering, Clemson University, Clemson, SC, USA. brbooth@clemson.edu.

Abstract

Purpose: Currently, tumor-treating field (TTField) therapy utilizes a single "optimal" frequency of electric fields to achieve maximal cell death in a targeted population of cells. However, because of differences in cell size, shape, and ploidy during mitosis, optimal electric field characteristics for universal maximal cell death may not exist. This study investigated the anti-mitotic effects of modulating electric field frequency as opposed to utilizing uniform electric fields.

Methods: We developed and validated a custom device that delivers a wide variety of electric field and treatment parameters including frequency modulation. We investigated the efficacy of frequency modulating tumor-treating fields on triple-negative breast cancer cells compared to human breast epithelial cells.

Results: We show that frequency-modulated (FM) TTFields are as selective at treating triple-negative breast cancer (TNBC) as uniform TTFields while having a greater efficacy for combating TNBC cell growth. TTField treatment at a mean frequency of 150 kHz with a frequency range of ± 10 kHz induced apoptosis in a greater number of TNBC cells after 24 h as compared to unmodulated treatment which led to further decreased cell viability after 48 h. Furthermore, all TNBC cells died after 72 h of FM treatment while cells that received unmodulated treatment were able to recover to cell number equivalent to the control.

Conclusion: TTFields were highly efficacious against TNBC growth, FM TTFields showed minimal effects on epithelial cells similar to unmodulated treatment.

Keywords: Breast cancer; Electric field intensity; Frequency modulation; Oscillating electric fields; Radiotherapy; Triple-negative breast cancer (TNBC); Tumor-treating fields (TTFields).