Non-thermal ablation and drug delivery by electroporation: expanding current indications beyond cancer and cardiac treatment

BACKGROUND: Electroporation-Based Treatments and Therapies (EBTTs) - electrochemotherapy, irreversible electroporation, pulsed field ablation, and gene electro-transfer - use short, high-voltage electric pulses to permeabilize cell membranes, enabling non-thermal tissue ablation and enhanced local drug delivery. Although EBTTs have been used clinically for over three decades, primarily in oncology, their adoption remains limited compared to thermal ablation modalities. In contrast, cardiac pulsed field ablation (PFA) has seen rapid adoption since the first FDA device approval in December 2023. CONCLUSIONS: This expert opinion paper reviews the current clinical landscape of EBTTs in oncology and cardiac arrhythmia treatments, and focuses on emerging non-oncological and non-cardiac applications, including endoscopic pulsed electric field therapy for type 2 diabetes, bronchial rheoplasty for chronic bronchitis, bleomycin electrosclerotherapy for vascular malformations, nanosecond PFA for benign thyroid nodules, and electroporation-mediated gene delivery - and identifies key barriers to wider adoption: insufficient randomized evidence, lack of validated treatment planning tools, fragmented reimbursement, and limited standardization. We outline measures to facilitate clinical translation.