Enormous progress has been made in pulsed electric field-based therapies since J.
Teissié reported the occurrence of electric field-induced transient pores in phospholipid
bilayer vesicles in 1981 . The transient pores, which occurred upon application
of short (microsecond) external electric field pulses were attributed to the dielectric
breakdown of the bilayer structure and did not damage the lipid membrane . While
the term “electroporation” (also known as electropermeabilization or the formation
of transient permeant structures) took some time to anchor within the vocabulary of
the entire scientific community, experiments showed that pulsed electric field could
have numerous biological consequences. Among them, the induction of ATP synthesis
, onset of cell fusion , generation of cell hybrids , induction of cytoskeletal
reorganization , transfection of cells [6,7,8], delivery of molecules including
cytotoxic drugs to cells , and anticancer therapy  set the bases for therapeutic
This Special Issue covers a number of hot topics in the field of electric field based
therapies in cancer treatment. Original research and a review article present recent
advances in calcium electroporation [11,12,13,14], the potential of expandable electrodes
is presented in a porcine model undergoing open body surgery, laparoscopy and endoscopy
, and the extension of the time of blood brain barrier disruption is highlighted
after application of high frequency electroporation . In addition to a review
providing the state of the art in cytoskeletal alterations after electroporation ,
original research articles also present the induction of immunogenic cell death by
nanosecond pulsed electric fields  and describe protocols for the optimization
of DNA electrotransfer [19,20].
In addition to electrochemotherapy and irreversible electroporation, that already
proved their efficacy to treat cancer, the combination of calcium ions with high intensity
electric field pulses is emerging in clinics. As calcium ions are implicated in cell
death regulation, the amplification of calcium ions uptake upon electropermeabilization
results in acute and severe ATP depletion associated with cancer cell death. This
approach has been used in clinics and the treatment modality is thoroughly reviewed
by Frandsen et al. . In addition to this comprehensive review, Agoston et al.
 presented a Phase II Clinical trial (NCT03628417) where they compared the efficacy
of calcium-based electroporation with bleomycin-based electrochemotherapy. The two
approaches lead to a similar tumor response but adverse reactions, such as ulceration
and hyperpigmentation, were less common after calcium-based electroporation .
Moreover, as highlighted by Gibot et al. , calcium electroporation is not genotoxic.
In addition to electrochemotherapy protocols, calcium ions were shown to delay tumor
growth upon combination with irreversible electroporation, as reported by Novickij
et al. . Their protocol was not only efficient against primary tumors in a murine
model, but also destroyed the tumor microenvironment and induced anti-tumor immune
response. A similar phenomenon of immunostimulation was also observed by Rossi et
al. , who applied nanosecond pulsed electric fields in murine cancer models.
Significant advances were made in electric field-based delivery of DNA  to cancer
cells. Indeed, protocols still need to be optimized. In this context, Sieni et al.
 described a useful three-dimensional cellular scaffold, which is rich in extracellular
matrix and appears particularly attractive for gene electro transfer studies. As electrotransfer
may decrease cell viability, Wang et al.  show that inhibition of caspases post
electrotransfer may significantly increase cell viability, without compromising the
T cell receptor disruption efficiency.
High frequency electroporation was efficiently used to transiently disrupt the blood
brain barrier in vivo in a healthy rat brain model, as shown by Lorenzo et al. .
In the mentioned study, the blood brain barrier could remain focally disrupted for
72 h following the application of high frequency electroporation, and returned to
its normal 96 h following pulse exposures. This finding thus suggests a useful approach
to permeate the blood brain barrier and promote drug diffusion into brain parenchyma.
Last but not least, this special issue also includes a review by Graybill et al. 
describing cytoskeletal disruption after cellular exposure to pulsed electric fields.
This extensive review summarizes nearly 200 studies describing cytoskeletal disruption
 englobing Teissié’s pioneering works  and a series of cutting-edge papers
detailing the mechanisms and outcomes of cytoskeletal disruption.
We hope that this Special Issue will be of interest to a vast number of researchers
and that it will encourage new ideas and scientific discoveries. The editors are highly
grateful to the editor in chief, editorial staff, reviewers, and to all contributors.
We look forward to meeting you again at the forthcoming 4th World Congress in September
2021 in Copenhagen, Denmark.