Abstract PS18-21: Pulsed electric field exposure (PEFE) applied in breast cancer: A potential normothermic clinical cancer therapy
Authors: Tracey Martin, Zhe Zhao, Chang Gong, Shuo Cai, Fiona Ruge, Philippa Young, Robert E Mansel, Johannes Benedikt, Wen G Jiang
Journal: Cancer Research (2021)

Abstract Background: Current and existing ablation for cancer treatment such as laser, RF and MW, all induce local high temperatures. The hyperthermia generated by these techniques lead to burns, pain and unwanted side effects in patients. Consequently, we aimed to develop a normothermic pulsed electric field exposure (PEFE) treatment that when applied in cancer treatments can effectively induce cell death and tumour degeneration without associated physical consequences. Method: The pulsed electric field exposure (PEFE) was generated with a carrier signal at 5.8GHz, then transmitted by a pointed open-ended coaxial cable. Breast cancer cells were treated with PEFE and assessed for their viability, apoptosis and other biological responses, together with the intracellular signalling events by using protein kinase array and related technologies. Breast cancer cells were also assessed for their ultrastructure changes by electron microscopy. In vivo experimentation was used to determine efficacy using human breast cancer tumour models in which tumours were treated with short PEFE pulses. The temperature at the area of treatment was monitored to ensure normothermic conditions. Tumour size were checked every 3 days for 36 days duration following different treatment protocols, followed by histological and biochemical analyses of the tumour and surrounding tissues. Results: MDA-MB-231 cancer cells were subject to PEFE, which induced no temperature change. Cells react to different pulse regimes and is related to cell type and aggressiveness. The treated cells became apoptotic after 4 hrs and this continued for at least 24 h after exposure with a 70% death rate. The apoptotic changes were confirmed by both immunofluorescent based and electron microscopy based methods. Protein kinase array (Kinexustm) revealed that PEFE exposure resulted in marked signature changes in the intracellular signalling event leading to apoptosis, including (BCL2, the CHK family, EGFR and ERK). In the in vivo trial, tumours were allowed to reach approximately 0.5 cm3 before treatment with PEFE with multiple conditions, which all resulted in a significant reduction of tumour volume after one week (p&amp;lt;0.01 vs control). Three weeks after the PEFE treatment, most tumours were found to have disappeared with no detectable scarring and detectable side effects. Histological and biochemical analyses revealed the concurrent changes in both Caspase3 and BCL2 in PEFE treated tumours. Conclusion: Normothermic PEFE can induce cancer cell death in vitro and marked tumour reduction in vivo. Compared to existing thermal ablation techniques, PEFE does not induce high temperatures locally and therefor there is no influence on surrounding normal tissue. This technique has potential in minimally invasive surgery in cancer therapy for those unable to undergo general surgery or receive current chemo- or radiotherapies. Citation Format: Tracey Martin, Zhe Zhao, Chang Gong, Shuo Cai, Fiona Ruge, Philippa Young, Robert E Mansel, Johannes Benedikt, Wen G Jiang. Pulsed electric field exposure (PEFE) applied in breast cancer: A potential normothermic clinical cancer therapy [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS18-21.