// Hugo Jimenez 1 , Denise Gibo 2 , Sambad Sharma 2 , Michael Pennison 2 , Lance D. Miller 2 , Minghui Wang 2 , Kimberly Sheffield 1 , Liyue Zhang 1 , Allan Johansen 2 , Preeya Achari 2 , Callum Mcgrath 2 , Sean Lester 2 , Jason Tang 2 , Kojo Agyemang 2 , Annette Johnson 3 , Christopher T. Whitlow 4 , Michael Chan 5 , Kounosuke Watabe 2 , Ralph D'Agostino Jr. 2 , Janaka Liyanage 1 , Asfar Azmi 1 , Geoffrey Barger 6 , Alexandre Barbault 7 , Glenn J. Lesser 8 , Waldemar Debinski 2 and Boris C. Pasche 1 1 Department of Oncology, Wayne State University School of Medicine/Karmanos Cancer Institute, Detroit, MI 48201, USA 2 Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC 27101, USA 3 Medical College of Georgia at Augusta University, Augusta, GA 30912, USA 4 Department of Radiology, Atrium Health Wake Forest Baptist Medical Center, Winston-Salem, NC 27103, USA 5 Department of Radiation Oncology, Atrium Health Wake Forest Baptist Medical Center, Winston-Salem, NC 27103, USA 6 Department of Neurology, Wayne State University, Detroit, MI 48202, USA 7 TheraBionic GmbH, Ettlingen, Germany 8 Department of Internal Medicine, Section on Hematology/Oncology, Atrium Health Wake Forest Baptist Medical Center, Winston-Salem, NC 27157, USA Correspondence to: Hugo Jimenez, email: hugo.jimenez@wayne.edu Keywords: amplitude-modulated radiofrequency electromagnetic fields; glioblastoma; TheraBionic; CACNA1H; Ca v 3.2 Received: March 04, 2025 Accepted: September 25, 2025 Published: October 13, 2025 Copyright: © 2025 Jimenez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT Background: Intrabuccal administration of amplitude-modulated 27.12 MHz radiofrequency electromagnetic fields (AM RF EMF) resulting in the systemic delivery of low and safe levels of AM RF EMF has shown activity in several forms of cancer. Methods: Glioblastoma (GB) cell lines were exposed to GB-specific AM RF EMF (GBMF) three hours per day at a level of exposure identical to patients during treatment. Cellular assays and agnostic genomic approaches were used to characterize the mechanism-of-action. One patient with therapy refractory GB received compassionate use treatment with GBMF as well as a second patient with refractory oligodendroglioma. Results: Treatment with GBMF inhibited the proliferation of several GB cell lines. CACNA1H mediates the effect of GBMF. GBMF modulates the "Mitotic Roles of Polo-Like Kinase" pathway resulting in the disruption of GB mitotic spindle. There was evidence of clinical and radiological benefit in a 38-year-old patient with recurrent GB and evidence of safety and feasibility in a 47-year-old patient with oligodendroglioma. Conclusions: This is the first report showing in vitro antitumor activity, disruption of the mitotic spindle, activation of the Mitotic Roles of Polo-like kinase pathway in GB. This is also the first report showing feasibility and clinical activity in patients with brain tumor.
Jimenez et al. (Mon,) studied this question.