Electroporation-Based Therapy for Brain Tumors: A Review

Abstract

Electroporation-based therapy (EBT), as a high-voltage-pulse technology has been prevalent with favorable clinical outcomes in the treatment of various solid tumors. The aim of this review paper is to promote the clinical translation of EBT for brain tumors. First, we briefly introduced the mechanism of pore formation in a cell membrane activated by external electric fields using a single cell model. Then, we summarized and discussed the current in vitro and in vivo preclinical studies, in terms of (1) the safety and effectiveness of EBT for brain tumors in animal models, and (2) the blood-brain barrier (BBB) disruption induced by EBT. Two therapeutic effects could be achieved in EBT for brain tumors simultaneously, i.e., the tumor ablation induced by irreversible electroporation (IRE) and transient blood-brain barrier (BBB) disruption induced by reversible electroporation (RE). The BBB disruption could potentially improve the uptake of anti-tumor drugs thereby enhancing brain tumor treatment. The challenges that hinder the application of EBT in the treatment of human brain tumors are discussed in the review paper as well.

An Investigation for Large Volume, Focal Blood-Brain Barrier Disruption with High-Frequency Pulsed Electric Fields

“…We report minor differences in BBBd thresholds across waveforms with a maximum difference of 82.7 V/cm and differences in ablation thresholds of up to 519.7 V/cm. The mechanism of BBBd is suggested to be linked to the disruption of the tight junction proteins [ 19 ], making this phenomenon physiologically distinct from the mechanisms of electroporation. Taking advantage of this threshold gap, we can implement a BBBd maximization protocol by utilizing the waveform with the most considerable differences in these thresholds.…”

“…To enhance CNS drug delivery, previous studies support the use of electroporation-based therapies (EBTs) to focally [ 17 ] and transiently [ 18 ] disrupt the blood-brain barrier [ 19 ]. EBTs are a collection of therapies that employ pulsed electric fields (PEFs) to increase the transmembrane potential of a cell [ 20 ].…”

“…Specifically, high-frequency irreversible electroporation (H-FIRE) is an EBT capable of disrupting the BBB [ 26 ] and inducing selective cell death between malignant and healthy phenotypes [ 27 ]. The safety and feasibility of tissue ablation with H-FIRE have been investigated for the treatment of intracranial meningioma in a spontaneous canine brain tumor model [ 28 ], while the predecessor to this technology, named irreversible electroporation (IRE), has demonstrated the efficacious ablation of high-grade gliomas in canine patients presenting with spontaneous brain tumors [ 19 ].…”

Comprehensive review on thermal aspects of nonthermal irreversible electroporation

“…However, long pulses cause vigorous body movements because of muscle contraction. Subsequently, the usefulness of biphasic pulses (Figure 3B), in which electric pulses with shorter widths are applied while switching poles, has been demonstrated 78–80 . A new procedure called high‐frequency irreversible electroporation (H‐FIRE) employs a few microseconds of bipolar pulses in a burst, 61,81 while ablation using nanosecond electric pulses (nsEP) has also been proposed 78,79,82 .…”

Irreversible Electroporation Mediates Glioma Apoptosis via Upregulation of AP-1 and Bim: Transcriptome Evidence

“…Moreover, IRE effectively protects vascular networks within treated areas. These make it a suitable therapeutic candidate for GBM [ 10 ]. Within the field of GBM treatment, there was only modest evidence of animal research and in vitro cell experiments for IRE [ 11 , 12 ].…”