Abstract 1833: Assessment of shifts in tumor-specific frequencies on the proliferation of hepatocellular carcinoma cells

Abstract Background: Radiofrequency Electromagnetic Fields Amplitude-Modulated at tumor-specific frequencies (AM RF EMF) are FDA approved for the treatment of advanced hepatocellular carcinoma (HCC) and have been shown to inhibit cancer growth in vitro, in vivo, and in clinical trials. The mechanism behind AM RF EMF induced proliferative inhibition is intracellular Ca2+ influx via the Cav3.2 T-type calcium ion channel exclusively within malignant cells. However, it is unknown how AM RF EMF opens the Cav3.2 channel. We hypothesize that the tumor specific frequencies are the natural frequencies of the malignant Cav3.2 channels and thus AM RF EMF is a resonance phenomenon. To test this, we first assessed the impact on proliferative inhibition from the RF carrier wave and ambient magnetic fields. We then shifted base HCC treatment frequencies from +0.1 Hz to +0.0001 Hz logarithmically and compared proliferative inhibition to base treatment frequencies. Methods: Huh7, Hep3B and SNU-423 HCC cell lines were treated with HCC-specific AM RF EMF under two conditions: normal incubator conditions, and within a magnetically shielded metal box. Growth inhibition relative to control was measured between the two groups via thymidine incorporation assay. Next, Huh7 and Hep3B cells were exposed to the unmodulated 27.12 MHz RF carrier wave and growth inhibition compared to control via thymidine incorporation assay. Lastly, Huh7 and Hep3B cells were treated with HCC AM RF EMF frequencies shifted by either +0.1 Hz, +0.01 Hz, +0.001 Hz, or +0.0001 Hz. Growth inhibition relative to standard treatment was measured via thymidine incorporation assay. Results: There was no change in growth for Huh7 and Hep3B cells exposed to the unmodulated carrier wave compared to their respective controls. There was no change in proliferative inhibition between normal and magnetically shielded conditions for Huh7, Hep3B, and SNU-423 cells. All frequency shifts resulted in significantly decreased treatment efficacy relative to base frequencies (+0.0001 Hz: p = 0.0021, +0.001 Hz: p = 0.0172, +0.01 Hz: p = 0.0145, and +0.1 Hz: p = 0.0279) Conclusion: Neither the unmodulated carrier wave nor ambient magnetic fields contribute to AM RF EMF induced proliferative inhibition. AM RF EMF is not a resonance phenomenon but is highly sensitive to small fluctuations in treatment frequencies, highlighting the specificity required for optimal treatment. Citation Format: Callum T. McGrath, Preeya F. Achari, Carl Blackman, Janaka P. Liyanage, Hugo Jimenez, Boris C. Pasche. Assessment of shifts in tumor-specific frequencies on the proliferation of hepatocellular carcinoma cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1833.