Abstract 330: Treatment of fibrolamellar carcinoma with hepatocellular carcinoma -specific amplitude-modulated radiofrequency electromagnetic fields

Abstract Background: Amplitude-modulated 27.12 MHz radiofrequency electromagnetic fields (AM RF EMF) delivered via a spoon-shaped antenna placed on the patient’s tongue result in shrinkage of the primary and metastatic tumors in patients with advanced hepatocellular carcinoma (HCC). The mechanism by which AM RF EMF has a direct antiproliferative effect has been found to be dependent on the influx of extracellular Ca2+ into the cancer cell via CaV3.2 (gene name CACNA1H) T-type voltage-gated calcium channel. Fibrolamellar Carcinoma (FLC), a rare subtype of HCC, has few options available for treatment. Here we present, for the first time, data showing that HCC-specific AM RF EMF (HCCMF) are effective in FLC. Methods: HepG2 is an HCC cell line and H33 (HepG2DNAJB1-PRKACA) was generated by using the HepG2 cell line and generating the DNAJB1-PRKACA gene fusion at the native locus (CRISPR-based 400kbp excision). Cells either received no treatment (SHAM) or were exposed to HCCMF three hours per day for seven days total. HepG2 and H33 cells were exposed using systems replicating human exposure levels and treatment duration. In vitro experiments (colony formation and tumor sphere formation) with HepG2 and H33 cells were performed. Two-tailed Student’s t-test was used for statistical comparison. Results: Proliferation (colony formation assay) of HepG2 and H33 is inhibited by 37.54% (p-value: 0.0023, N=6) and 27.08% (p-value: 0.0006, N=6), respectively. Stemness (tumor sphere formation assay) of HepG2 and H33 is inhibited by 33.17% (p-value < 0.0001, N=8 SHAM and N=7 HCCMF) and 43.95% (p-value< 0.0001, N=7 SHAM and N=8 HCCMF), respectively. Conclusions: Proliferation and stemness of the HepG2 and H33 [HepG2 (DNAJB1-PRKACA)] cell lines were inhibited following HCCMF treatment. Results show the presence of the FLC fusion protein (DNAJB1-PRKACA) does not inhibit the potential of HCCMF as a novel systemic targeted therapy for FLC. This proof-of-principle data shows significant potential for the treatment of FLC. Citation Format: Hugo Jimenez, Liyue Zhang, Grayson Barker, Callum McGrath, Allan M. Johansen, Janaka S. Liyanage, Mohammed N. Al Hallak, Anthony F. Shields, Wasif Saif, Husian Y. Khan, Amro aboukameel, Hafiz Uddin, Sahar F. Bannoura, Ramzi Mohammad, Sean Ronnekleiv-Kelly, Alexandre Barbault, Carl F. Blackman, Asfar Azmi, Boris Pasche. Treatment of fibrolamellar carcinoma with hepatocellular carcinoma -specific amplitude-modulated radiofrequency electromagnetic fields. [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 330.