Electric Field Based Therapies in Cancer Treatment: a Selection of Studies Presented at the 3rd World Congress on Electroporation

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (30 April 2020) | Viewed by 48501

Special Issue Editors


E-Mail Website
Guest Editor
Institute of Pharmacology and Structural Biology, 205 Route de Narbonne, 31400 Toulouse, France
Interests: inorganic nanoparticles; endocytosis; particokinetics; pulsed electric fields; vectorization; magnetic hyperthermia; photothermal therapy; tumor microenvironment
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
Institut de Pharmacologie et de Biologie Structurale, IPBS CNRS (UMR 5089), Universite de Toulouse, 31077 Toulouse, France
Interests: electroporation; electrochemotherapy; cellular biophysics; gene transfer; nanoparticles; cell membrane; imaging; vectorization
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
Institute of Pharmacology and Structural Biology, 205 Route de Narbonne, Toulouse 31400, France
Interests: electroporation; electrochemotherapy; irreversible electroporation; gene therapy; non-viral drug delivery; optical imaging; DNA vaccine; nanoparticles

Special Issue Information

Dear Colleagues,

We are pleased to announce the call for a Special Issue, which will encompass selected studies, presented at the “3rd World Congress on Electroporation and Pulsed Electric Fields in Biology, Medicine, Food and Environmental Technologies (wc2019.electroporation.net)”, which will take place in Toulouse, France on 3–6 September 2019.

This cross- and multidisciplinary meeting is organized by the “International Society of Electroporation Based Technologies and Treatments”, and will bring together scientists, clinicians and industrials with a shared interest in electric field based approaches.

The international conference represents the major event for the scientific community working on electric field based therapies and industrial approaches involving pulsed electric fields, and will include topics related to basic biology, computational modeling of electroporation, pulsed electric field technologies, biomedical applications, food processing, environmental applications, micro and nanotechnologies, and cold plasma.

This Special Issue will cover the latest research pertaining to electroporation and electric field based technologies and their therapeutic applications, principally but not exclusively applied to cancer treatments. This compendium will cover novel research studies and reviews, related to basic as well as applied research related to electric field based therapies.

Dr. Jelena Kolosnjaj-Tabi
Dr. Marie-Pierre Rols
Dr. Muriel Golzio
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.

Further information on MDPI's Special Issue polices can be found here.

Published Papers (11 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Editorial

Jump to: Research, Review

3 pages, 204 KiB  
Editorial
Electric Field Based Therapies in Cancer Treatment
by Marie-Pierre Rols, Muriel Golzio and Jelena Kolosnjaj-Tabi
Cancers 2020, 12(11), 3420; https://doi.org/10.3390/cancers12113420 - 18 Nov 2020
Cited by 4 | Viewed by 1986
Abstract
Enormous progress has been made in pulsed electric field-based therapies since J [...] Full article

Research

Jump to: Editorial, Review

15 pages, 3654 KiB  
Article
Inhibition of Caspases Improves Non-Viral T Cell Receptor Editing
by Chunxi Wang, Chun-Chi Chang, Liangli Wang and Fan Yuan
Cancers 2020, 12(9), 2603; https://doi.org/10.3390/cancers12092603 - 11 Sep 2020
Cited by 7 | Viewed by 3503
Abstract
T cell receptor (TCR) knockout is a critical step in producing universal chimeric antigen receptor T cells for cancer immunotherapy. A promising approach to achieving the knockout is to deliver the CRISPR/Cas9 system into cells using electrotransfer technology. However, clinical applications of the [...] Read more.
T cell receptor (TCR) knockout is a critical step in producing universal chimeric antigen receptor T cells for cancer immunotherapy. A promising approach to achieving the knockout is to deliver the CRISPR/Cas9 system into cells using electrotransfer technology. However, clinical applications of the technology are currently limited by the low cell viability. In this study, we attempt to solve the problem by screening small molecule drugs with an immortalized human T cell line, Jurkat clone E6-1, for inhibition of apoptosis. The study identifies a few caspase inhibitors that could be used to simultaneously enhance the cell viability and the efficiency of plasmid DNA electrotransfer. Additionally, we show that the enhancement could be achieved through knockdown of caspase 3 expression in siRNA treated cells, suggesting that the cell death in electrotransfer experiments was caused mainly by caspase 3-dependent apoptosis. Finally, we investigated if the caspase inhibitors could improve TCR gene-editing with electrotransferred ribonucleoprotein, a complex of Cas9 protein and a T cell receptor-α constant (TRAC)-targeting single guide RNA (sgRNA). Our data showed that inhibition of caspases post electrotransfer could significantly increase cell viability without compromising the TCR disruption efficiency. These new findings can be used to improve non-viral T cell engineering. Full article
Show Figures

Figure 1

19 pages, 9347 KiB  
Article
The Efficiency of Gene Electrotransfer in Breast-Cancer Cell Lines Cultured on a Novel Collagen-Free 3D Scaffold
by Elisabetta Sieni, Monica Dettin, Mariangela De Robertis, Bianca Bazzolo, Maria Teresa Conconi, Annj Zamuner, Ramona Marino, Flavio Keller, Luca Giovanni Campana and Emanuela Signori
Cancers 2020, 12(4), 1043; https://doi.org/10.3390/cancers12041043 - 23 Apr 2020
Cited by 17 | Viewed by 4640
Abstract
Gene Electro-Transfer (GET) is a powerful method of DNA delivery with great potential for medical applications. Although GET has been extensively studied in vitro and in vivo, the optimal parameters remain controversial. 2D cell cultures have been widely used to investigate GET protocols, [...] Read more.
Gene Electro-Transfer (GET) is a powerful method of DNA delivery with great potential for medical applications. Although GET has been extensively studied in vitro and in vivo, the optimal parameters remain controversial. 2D cell cultures have been widely used to investigate GET protocols, but have intrinsic limitations, whereas 3D cultures may represent a more reliable model thanks to the capacity of reproducing the tumor architecture. Here we applied two GET protocols, using a plate or linear electrode, on 3D-cultured HCC1954 and MDA-MB231 breast cancer cell lines grown on a novel collagen-free 3D scaffold and compared results with conventional 2D cultures. To evaluate the electrotransfer efficiency, we used the plasmid pEGFP-C3 encoding the enhanced green fluorescent protein (EGFP) reporter gene. The novel 3D scaffold promoted extracellular matrix deposition, which particularly influences cell behavior in both in vitro cell cultures and in vivo tumor tissue. While the transfection efficiency was similar in the 2D-cultures, we observed significant differences in the 3D-model. The transfection efficiency in the 3D vs 2D model was 44% versus 15% (p < 0.01) and 24% versus 17% (p < 0.01) in HCC1954 and MDA-MB231 cell cultures, respectively. These findings suggest that the novel 3D scaffold allows reproducing, at least partially, the peculiar morphology of the original tumor tissues, thus allowing us to detect meaningful differences between the two cell lines. Following GET with plate electrodes, cell viability was higher in 3D-cultured HCC1954 (66%) and MDA-MB231 (96%) cell lines compared to their 2D counterpart (53% and 63%, respectively, p < 0.001). Based on these results, we propose the novel 3D scaffold as a reliable support for the preparation of cell cultures in GET studies. It may increase the reliability of in vitro assays and allow the optimization of GET parameters of in vivo protocols. Full article
Show Figures

Figure 1

17 pages, 19039 KiB  
Article
New Deployable Expandable Electrodes in the Electroporation Treatment in a Pig Model: A Feasibility and Usability Preliminary Study
by Francesco Izzo, Franco Ionna, Vincenza Granata, Vittorio Albino, Renato Patrone, Francesco Longo, Agostino Guida, Paolo Delrio, Daniela Rega, Dario Scala, Roberto Pezzuto, Roberta Fusco, Elio Di Bernardo, Valeria D’Alessio, Roberto Grassi, Deyanira Contartese and Raffaele Palaia
Cancers 2020, 12(2), 515; https://doi.org/10.3390/cancers12020515 - 23 Feb 2020
Cited by 11 | Viewed by 3811
Abstract
The aim of the study is to evaluate the usability aspects of new deployable, expandable, electrode prototypes, in terms of suitability solutions for laparoscopic applications on the liver, endoscopic trans-oral and trans-anal procedures, electroporation segmentation in several steps, mechanical functionality (flexibility, penetrability), visibility [...] Read more.
The aim of the study is to evaluate the usability aspects of new deployable, expandable, electrode prototypes, in terms of suitability solutions for laparoscopic applications on the liver, endoscopic trans-oral and trans-anal procedures, electroporation segmentation in several steps, mechanical functionality (flexibility, penetrability), visibility of the electrode under instrumental guidance, compatibility of the electrode with laparoscopic/endoscopic accesses, surgical instruments, and procedural room and safety compatibility. The electroporation was performed on an animal model (Sus Scrofa Large White 60 kg) both in laparoscopy and endoscopy, under ultrasound guidance, and in open surgery. Electrodes without divergence, with needles coming out straight, parallel to each other, and electrodes with peripheral needles (four needles), diverging from the electrode shaft axis (electrode with non-zero divergence) have been tested. To cause an evaluable necrosis effect, the number of electrical pulses was increased to induce immediate liver cell death. Histological samples were analyzed by staining with Haematoxylin/Eosin or by immunohistochemical staining to confirm complete necrosis. The prototypes of expandable electrodes, tested in laparoscopy and endoscopy and in open surgery, respectively, are suitable in terms of usability, electroporation segmentation in several steps, mechanical functionality (flexibility, penetrability), visibility under instrumental guidance, compatibility with laparoscopic/endoscopic accesses, surgical instruments and procedural room safety, patient safety (no bleeding and/or perforation), and treatment efficacy (adequate ablated volume). Electroporation treatment using new deployable expandable electrode prototypes is safe and feasible. Moreover, electrode configurations allow for a gradual increase in the ablated area in consecutive steps, as confirmed by histology and immunohistochemistry. Full article
Show Figures

Figure 1

17 pages, 6222 KiB  
Article
Calcium Delivery by Electroporation Induces In Vitro Cell Death through Mitochondrial Dysfunction without DNA Damages
by Laure Gibot, Audrey Montigny, Houda Baaziz, Isabelle Fourquaux, Marc Audebert and Marie-Pierre Rols
Cancers 2020, 12(2), 425; https://doi.org/10.3390/cancers12020425 - 12 Feb 2020
Cited by 34 | Viewed by 4490
Abstract
Adolescent cancer survivors present increased risks of developing secondary malignancies due to cancer therapy. Electrochemotherapy is a promising anti-cancer approach that potentiates the cytotoxic effect of drugs by application of external electric field pulses. Clinicians proposed to associate electroporation and calcium. The current [...] Read more.
Adolescent cancer survivors present increased risks of developing secondary malignancies due to cancer therapy. Electrochemotherapy is a promising anti-cancer approach that potentiates the cytotoxic effect of drugs by application of external electric field pulses. Clinicians proposed to associate electroporation and calcium. The current study aims to unravel the toxic mechanisms of calcium electroporation, in particular if calcium presents a genotoxic profile and if its cytotoxicity comes from the ion itself or from osmotic stress. Human dermal fibroblasts and colorectal HCT-116 cell line were treated by electrochemotherapy using bleomycin, cisplatin, calcium, or magnesium. Genotoxicity, cytotoxicity, mitochondrial membrane potential, ATP content, and caspases activities were assessed in cells grown on monolayers and tumor growth was assayed in tumor spheroids. Results in monolayers show that unlike cisplatin and bleomycin, calcium electroporation induces cell death without genotoxicity induction. Its cytotoxicity correlates with a dramatic fall in mitochondrial membrane potential and ATP depletion. Opposite of magnesium, over seven days of calcium electroporation led to spheroid tumor growth regression. As non-genotoxic, calcium has a better safety profile than conventional anticancer drugs. Calcium is already authorized by different health authorities worldwide. Therefore, calcium electroporation should be a cancer treatment of choice due to the reduced potential of secondary malignancies. Full article
Show Figures

Figure 1

14 pages, 3106 KiB  
Article
Evaluation of Calcium Electroporation for the Treatment of Cutaneous Metastases: A Double Blinded Randomised Controlled Phase II Trial
by Dóra Ágoston, Eszter Baltás, Henriette Ócsai, Sándor Rátkai, Péter Gy Lázár, Irma Korom, Erika Varga, István Balázs Németh, Éva Dósa-Rácz Viharosné, Julie Gehl, Judit Oláh, Lajos Kemény and Erika Gabriella Kis
Cancers 2020, 12(1), 179; https://doi.org/10.3390/cancers12010179 - 10 Jan 2020
Cited by 41 | Viewed by 3991
Abstract
Calcium electroporation (Ca-EP) is a new anticancer treatment providing similar features to electrochemotherapy (ECT). The aim of our study is to compare the efficacy of Ca-EP with bleomycin-based ECT. This double-blinded randomized controlled phase II study was conducted at the Medical University of [...] Read more.
Calcium electroporation (Ca-EP) is a new anticancer treatment providing similar features to electrochemotherapy (ECT). The aim of our study is to compare the efficacy of Ca-EP with bleomycin-based ECT. This double-blinded randomized controlled phase II study was conducted at the Medical University of Szeged, Hungary. During this once only treatment up to ten measurable cutaneous metastases per patient were separately block randomized for intratumoral delivery of either calcium or bleomycin, which was followed by reversible electroporation. Tumour response was evaluated clinically and histologically six months after treatment. (ClinicalTrials.gov: NCT03628417, closed). Seven patients with 44 metastases (34 from malignant melanoma, 10 from breast cancer) were included in the study. Eleven metastases were taken for biopsies, and 33 metastases were randomised and treated once. The objective response rates were 33% (6/18) for Ca-EP and 53% (8/15) for bleomycin-based ECT, with 22% (4/18) and 40% (6/15) complete response rates, respectively. The CR was confirmed histologically in both arms. Serious adverse events were not registered. Ulceration and hyperpigmentation, both CTCA criteria grade I side effects, were observed more frequently after bleomycin-based ECT than for Ca-EP. Ca-EP was non-inferior to ECT, therefore, it should be considered as a feasible, effective and safe treatment option. Full article
Show Figures

Figure 1

18 pages, 2218 KiB  
Article
Nanosecond Pulsed Electric Fields Induce Endoplasmic Reticulum Stress Accompanied by Immunogenic Cell Death in Murine Models of Lymphoma and Colorectal Cancer
by Alessandra Rossi, Olga N. Pakhomova, Peter A. Mollica, Maura Casciola, Uma Mangalanathan, Andrei G. Pakhomov and Claudia Muratori
Cancers 2019, 11(12), 2034; https://doi.org/10.3390/cancers11122034 - 17 Dec 2019
Cited by 40 | Viewed by 5246
Abstract
Depending on the initiating stimulus, cancer cell death can be immunogenic or non-immunogenic. Inducers of immunogenic cell death (ICD) rely on endoplasmic reticulum (ER) stress for the trafficking of danger signals such as calreticulin (CRT) and ATP. We found that nanosecond pulsed electric [...] Read more.
Depending on the initiating stimulus, cancer cell death can be immunogenic or non-immunogenic. Inducers of immunogenic cell death (ICD) rely on endoplasmic reticulum (ER) stress for the trafficking of danger signals such as calreticulin (CRT) and ATP. We found that nanosecond pulsed electric fields (nsPEF), an emerging new modality for tumor ablation, cause the activation of the ER-resident stress sensor PERK in both CT-26 colon carcinoma and EL-4 lymphoma cells. PERK activation correlates with sustained CRT exposure on the cell plasma membrane and apoptosis induction in both nsPEF-treated cell lines. Our results show that, in CT-26 cells, the activity of caspase-3/7 was increased fourteen-fold as compared with four-fold in EL-4 cells. Moreover, while nsPEF treatments induced the release of the ICD hallmark HMGB1 in both cell lines, extracellular ATP was detected only in CT-26. Finally, in vaccination assays, CT-26 cells treated with nsPEF or doxorubicin equally impaired the growth of tumors at challenge sites eliciting a protective anticancer immune response in 78% and 80% of the animals, respectively. As compared to CT-26, both nsPEF- and mitoxantrone-treated EL-4 cells had a less pronounced effect and protected 50% and 20% of the animals, respectively. These results support our conclusion that nsPEF induce ER stress, accompanied by bona fide ICD. Full article
Show Figures

Figure 1

23 pages, 2969 KiB  
Article
Temporal Characterization of Blood–Brain Barrier Disruption with High-Frequency Electroporation
by Melvin F. Lorenzo, Sean C. Thomas, Yukitaka Kani, Jonathan Hinckley, Matthew Lee, Joy Adler, Scott S. Verbridge, Fang-Chi Hsu, John L. Robertson, Rafael V. Davalos and John H. Rossmeisl, Jr.
Cancers 2019, 11(12), 1850; https://doi.org/10.3390/cancers11121850 - 23 Nov 2019
Cited by 36 | Viewed by 3499
Abstract
Treatment of intracranial disorders suffers from the inability to accumulate therapeutic drug concentrations due to protection from the blood–brain barrier (BBB). Electroporation-based therapies have demonstrated the capability of permeating the BBB, but knowledge of the longevity of BBB disruption (BBBD) is limited. In [...] Read more.
Treatment of intracranial disorders suffers from the inability to accumulate therapeutic drug concentrations due to protection from the blood–brain barrier (BBB). Electroporation-based therapies have demonstrated the capability of permeating the BBB, but knowledge of the longevity of BBB disruption (BBBD) is limited. In this study, we quantify the temporal, high-frequency electroporation (HFE)-mediated BBBD in an in vivo healthy rat brain model. 40 male Fisher rats underwent HFE treatment; two blunt tipped monopolar electrodes were advanced into the brain and 200 bursts of HFE were delivered at a voltage-to-distance ratio of 600 V/cm. BBBD was verified with contrast enhanced T1W MRI (gadopentetate dimeglumine) and pathologically (Evans blue dye) at time points of 1, 24, 48, 72, and 96 h after HFE. Contrast enhanced T1W scans demonstrated BBBD for 1 to 72 h after HFE but intact BBB at 96 h. Histologically, tissue damage was restricted to electrode insertion tracks. BBBD was induced with minimal muscle contractions and minimal cell death attributed to HFE. Numerical modeling indicated that brief BBBD was induced with low magnitude electric fields, and BBBD duration increased with field strength. These data suggest the spatiotemporal characteristics of HFE-mediated BBBD may be modulated with the locally applied electric field. Full article
Show Figures

Figure 1

18 pages, 2460 KiB  
Article
Antitumor Response and Immunomodulatory Effects of Sub-Microsecond Irreversible Electroporation and Its Combination with Calcium Electroporation
by Vitalij Novickij, Robertas Čėsna, Emilija Perminaitė, Auksė Zinkevičienė, Dainius Characiejus, Jurij Novickij, Saulius Šatkauskas, Paulius Ruzgys and Irutė Girkontaitė
Cancers 2019, 11(11), 1763; https://doi.org/10.3390/cancers11111763 - 9 Nov 2019
Cited by 24 | Viewed by 3878
Abstract
In this work, we have investigated the feasibility of sub-microsecond range irreversible electroporation (IRE) with and without calcium electroporation in vivo. As a model, BALB/C mice were used and bioluminescent SP2/0 myeloma tumor models were developed. Tumors were treated with two separate pulsed [...] Read more.
In this work, we have investigated the feasibility of sub-microsecond range irreversible electroporation (IRE) with and without calcium electroporation in vivo. As a model, BALB/C mice were used and bioluminescent SP2/0 myeloma tumor models were developed. Tumors were treated with two separate pulsed electric field (PEF) pulsing protocols PEF1: 12 kV/cm × 200 ns × 500 (0.006 J/pulse) and PEF2: 12 kV/cm × 500 ns × 500 (0.015 J/pulse), which were delivered with and without Ca2+ (168 mM) using parallel plate electrodes at a repetition frequency of 100 Hz. Both PEF1 and PEF2 treatments reduced tumor growth and prolonged the life span of the mice, however, the PEF2 protocol was more efficient. The delay in tumor renewal was the biggest when a combination of IRE with calcium electroporation was used, however, we did not obtain significant differences in the final mouse survival compared to PEF2 alone. Anti-tumor immune responses were also investigated after treatment with PEF2 and PEF2+Ca. In both cases the treated mice had enlarged spleens and increased spleen T cell numbers, lower percentages of suppressor cell subsets (conventional CD4+CD25+ Treg, CD4+CD25DX5+ Tr1, CD8+DX5+, CD4+CD28, CD8+CD28), changed proportions of Tcm and Tef/Tem T cells in the spleen and increased amount of tumor cell specific antibodies in the sera. The treatment based on IRE was effective against primary tumors, destroyed the tumor microenvironment and induced an anti-tumor immune response, however, it was not sufficient for complete control of tumor metastasis. Full article
Show Figures

Figure 1

Review

Jump to: Editorial, Research

35 pages, 2130 KiB  
Review
Cytoskeletal Disruption after Electroporation and Its Significance to Pulsed Electric Field Therapies
by Philip M. Graybill and Rafael V. Davalos
Cancers 2020, 12(5), 1132; https://doi.org/10.3390/cancers12051132 - 30 Apr 2020
Cited by 44 | Viewed by 5204
Abstract
Pulsed electric fields (PEFs) have become clinically important through the success of Irreversible Electroporation (IRE), Electrochemotherapy (ECT), and nanosecond PEFs (nsPEFs) for the treatment of tumors. PEFs increase the permeability of cell membranes, a phenomenon known as electroporation. In addition to well-known membrane [...] Read more.
Pulsed electric fields (PEFs) have become clinically important through the success of Irreversible Electroporation (IRE), Electrochemotherapy (ECT), and nanosecond PEFs (nsPEFs) for the treatment of tumors. PEFs increase the permeability of cell membranes, a phenomenon known as electroporation. In addition to well-known membrane effects, PEFs can cause profound cytoskeletal disruption. In this review, we summarize the current understanding of cytoskeletal disruption after PEFs. Compiling available studies, we describe PEF-induced cytoskeletal disruption and possible mechanisms of disruption. Additionally, we consider how cytoskeletal alterations contribute to cell–cell and cell–substrate disruption. We conclude with a discussion of cytoskeletal disruption-induced anti-vascular effects of PEFs and consider how a better understanding of cytoskeletal disruption after PEFs may lead to more effective therapies. Full article
Show Figures

Graphical abstract

21 pages, 2712 KiB  
Review
A Comprehensive Review of Calcium Electroporation—A Novel Cancer Treatment Modality
by Stine K. Frandsen, Mille Vissing and Julie Gehl
Cancers 2020, 12(2), 290; https://doi.org/10.3390/cancers12020290 - 25 Jan 2020
Cited by 82 | Viewed by 7344
Abstract
Calcium electroporation is a potential novel anti-cancer treatment where high calcium concentrations are introduced into cells by electroporation, a method where short, high voltage pulses induce transient permeabilisation of the plasma membrane allowing passage of molecules into the cytosol. Calcium is a tightly [...] Read more.
Calcium electroporation is a potential novel anti-cancer treatment where high calcium concentrations are introduced into cells by electroporation, a method where short, high voltage pulses induce transient permeabilisation of the plasma membrane allowing passage of molecules into the cytosol. Calcium is a tightly regulated, ubiquitous second messenger involved in many cellular processes including cell death. Electroporation increases calcium uptake leading to acute and severe ATP depletion associated with cancer cell death. This comprehensive review describes published data about calcium electroporation applied in vitro, in vivo, and clinically from the first publication in 2012. Calcium electroporation has been shown to be a safe and efficient anti-cancer treatment in clinical studies with cutaneous metastases and recurrent head and neck cancer. Normal cells have been shown to be less affected by calcium electroporation than cancer cells and this difference might be partly induced by differences in membrane repair, expression of calcium transporters, and cellular structural changes. Interestingly, both clinical data and preclinical studies have indicated a systemic immune response induced by calcium electroporation. New cancer treatments are needed, and calcium electroporation represents an inexpensive and efficient treatment with few side effects, that could potentially be used worldwide and for different tumor types. Full article
Show Figures

Graphical abstract

Back to TopTop