Electroporation and Electrochemotherapy in Gynecological and Breast Cancer Treatment

Abstract

Gynecological carcinomas affect an increasing number of women and are associated with poor prognosis. The gold standard treatment plan is mainly based on surgical resection and subsequent chemotherapy with cisplatin, 5-fluorouracil, anthracyclines, or taxanes. Unfortunately, this treatment is becoming less effective and is associated with many side effects that negatively affect patients’ physical and mental well-being. Electroporation based on tumor exposure to electric pulses enables reduction in cytotoxic drugs dose while increasing their effectiveness. EP-based treatment methods have received more and more interest in recent years and are the subject of a large number of scientific studies. Some of them show promising therapeutic potential without using any cytotoxic drugs or molecules already present in the human body (e.g., calcium electroporation). This literature review aims to present the fundamental mechanisms responsible for the course of EP-based therapies and the current state of knowledge in the field of their application in the treatment of gynecological neoplasms.

Calcium Electroporation versus Electrochemotherapy with Bleomycin in an In Vivo CAM-Based Uveal Melanoma Xenograft Model

“…The administration of the tested agents, bleomycin and calcium, was carried out with an intratumoral injection of a 50 µL volume prior to EP in the according groups. Bleomycin remains the drug of choice and is well established for ECT, whereas the combination with calcium represents a novel treatment option due to the induced changes in calcium homeostasis in cancer cells [28,34,55,58,74,78,80]. The electrodes were placed directly on the CAM surface, and the tumor grafts were positioned between the two parallel aluminum rods.…”

“…However, they comprise thermal techniques, which may be affected by the heat sink effect, leading to incomplete ablation and thermal injuries of non-targeted surrounding structures. High-voltage pulsed electric field can induce the formation of aqueous nanopores in the cell membrane and an increased plasma membrane permeability [27,28]. This phenomenon is also known as electroporation.…”

Models of Irreversible Electroporation: A Review and Initial Model Implementation

“…Therefore, the IRE technique is considered a prospective alternative of thermal ablation techniques [3], [4]. There are reports that IRE can be used for treatment of cancers, among them liver, [3], [4], [5], [6], pancreas [5], [6] and prostate [6], [7], but also kidney [8], and breast [9].…”

Calcium Electrochemotherapy for Tumor Eradication and the Potential of High-Frequency Nanosecond Protocols

“…[ 8 , 9 ]. Depending on the pulsed power input, the formed pores in the cell membrane can be transient (reversible EP) or the cell plasma membrane can be disrupted permanently (irreversible EP) [ 7 , 10 ]. The methodology had shown clinical potential in cancer treatment as a tissue ablation method or when combined with initially non-permeant chemotherapeutics to increase their uptake (electrochemotherapy (ECT)) [ 5 , 6 , 11 ].…”

“…From the biophysical point of view, Ca 2+ is an essential second messenger ion involved in numerous vital cellular processes from transcription, proliferation, and metabolism to cell death [ 5 , 10 , 12 , 38 ]. In order to survive, the cells regulate intracellular calcium concentration, while in the presence of cell membrane permeabilization intracellular calcium concentration increases, this leads to adenosine triphosphate (ATP) depletion [ 35 , 36 ], mitochondrial dysfunction, and cell death by necrosis [ 12 , 14 , 34 , 38 , 39 ].…”