Abstract 329: Proliferative inhibition of pancreatic cancer cells treated with pancreatic cancer - specific amplitude-modulated radiofrequency electromagnetic fields

Abstract Background: Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related mortality, and about 50% of PDC patients present with metastatic disease. Despite advances in systemic therapy, the prognosis for PDC is dismal, with a five-year overall survival (OS) for metastatic PDC of about 5%. The most used regimens for advanced pancreatic cancer include gemcitabine/nab-paclitaxel (Gem/NabP) and FOLFIRINOX, with the recent addition of NALIRIFOX. All these regimens result in median survival rates under one year. Amplitude-modulated 27.12 MHz radiofrequency electromagnetic fields (AM RF EMF) delivered via a spoon-shaped antenna placed on the patient’s tongue results in shrinkage of the primary and metastatic tumors in patients with cancer. The mechanism by which AM RF EMF have 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. Here we present, for the first time, data showing that Pancreatic cancer-specific AM RF EMF (PancMF) is effective in pancreatic cancer cells. Methods: MIAPaCa-2 and PANC-1 cell lines were exposed either to no treatment (SHAM) to PancMF three hours per day for seven days total. Cell lines were exposed using systems replicating human exposure levels and treatment duration. Ethosuximide (Ethos), a pan t-type voltage gated calcium channel (VGCC) blocker was used to inhibit the effects of PancMF. In vitro experiments, (proliferation) Tritiated Thymidine incorporation and (stemness) tumor sphere formation were performed. ANOVA and Two-tailed Student’s t-test were used for comparison. Results: Panc1 cell line: Proliferation was inhibited 38.51% by PancMF treatment (p-value: <0.0001) but in the presence of ethosuximide PancMF proliferation inhibition was blocked (p-value: 0.9897). Stemness was inhibited 41.02% by PancMF treatment (p-value < 0.0001). MiaPaca2 cell line: Proliferation was inhibited 20.67% by PancMF treatment (p-value: 0.0208) but in the presence of ethosuximide PancMF proliferation inhibition was blocked (p-value: 0.8933). Stemness was inhibited 26.54% by PancMF treatment (p-value < 0.0001). Conclusions: Proliferation and Stemness of Panc1 and MiaPaca2 cell were inhibited following PancMF treatment, however, the presence of ethosuximide blocked the anti-proliferative effects of PancMF. Results indicate that the t-type VGCC mediates the anti-proliferative effect. This results trend with previously published data showing that Cav3.2 is the bioantenna and mediator for tumor-specific AM RF EMF treatment. Citation Format: Hugo Jimenez, Callum McGrath, Liyue Zhang, Grayson Barker, Allan M. Johansen, Janaka S. Liyanage, Mohammed N. Al Hallack, Anthony F. Shields, Wasif Saif, Husain Y. Khan, Amro Aboukameel, Hafiz Uddin, Sahar F. Bannoura, Ramzi M. Mohammad, Alexandre Barbault, Carl F. Blackman, Ravi K. Paluri, Asfar Azmi, Boris Pasche. Proliferative inhibition of pancreatic cancer cells treated with pancreatic cancer - 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 329.